| 1. |
- Andrén, Oliver C. J., et al.
(författare)
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Antibiotic-Free Cationic Dendritic Hydrogels as Surgical-Site-Infection-Inhibiting Coatings
- 2019
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Ingår i: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659.
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Tidskriftsartikel (refereegranskat)abstract
- A non-toxic hydrolytically fast-degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two-component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear-dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2-bis(hydroxymethyl)propionic acid, and ii) a di-N-hydroxysuccinimide functional poly(ethylene glycol) cross-linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged β-alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two-component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G' = 0.5-8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection.
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| 2. |
- Andrén, Oliver C. J., et al.
(författare)
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Therapeutic Nanocarriers via Cholesterol Directed Self-Assembly of Well-Defined Linear-Dendritic Polymeric Amphiphiles
- 2017
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Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 29:9, s. 3891-3898
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Tidskriftsartikel (refereegranskat)abstract
- A novel platform of fluorescently labeled nanocarriers (NCs) is herein proposed based on amphiphilic linear-dendritic polymeric hybrids. These sophisticated polymers were synthesized with a high degree of structural control at a macro-molecular level, displayed hydrophobic cholesterol compartments as chain-terminus groups of the dendritic block and hydrophilic bifunctional linear poly(ethylene glycol) (PEG) block. Spherical supramolecular assemblies with therapeutically relevant properties were successfully achieved including (i) sizes in the region of 100 to 200 nm; (ii) narrow dispersity profile with values close to 0.12; and (iii) self-assembly down to nanomolar concentrations. The modular nature of the NCs permitted the encapsulation of single or dual anticancer drugs and in parallel provide intracellular fluorescent traceability. As polymer therapeutics, the NCs were proven to penetrate the cancerous cell membranes and deliver the cargo of drugs into the nuclei as well as the cytoplasm and mitochondria. The dual drug delivery of both doxorubicin (DOX) and triptolide substantially enhanced the therapeutic efficacy with a 63% significant increase against resistant breast cancer cells when compared to free DOX.
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| 3. |
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| 4. |
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| 5. |
- Arseneault, Mathieu, et al.
(författare)
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The Dawn of Thiol-Yne Triazine Triones Thermosets as a New Material Platform Suited for Hard Tissue Repair
- 2018
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Ingår i: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095. ; 30:52
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Tidskriftsartikel (refereegranskat)abstract
- The identification of a unique set of advanced materials that can bear extraordinary loads for use in bone and tooth repair will inevitably unlock unlimited opportunities for clinical use. Herein, the design of high-performance thermosets is reported based on triazine-trione (TATO) monomers using light-initiated thiol-yne coupling (TYC) chemistry as a polymerization strategy. In comparison to traditional thiol-ene coupling (TEC) systems, TYC chemistry has yielded highly dense networks with unprecedented mechanical properties. The most promising system notes 4.6 GPa in flexural modulus and 160 MPa in flexural strength, an increase of 84% in modulus and 191% in strength when compared to the corresponding TATO system based on TEC chemistry. Remarkably, the mechanical properties exceed those of polylactide (PLA) and challenge poly(ether ether ketone) PEEK and today's methacrylate-based dental resin composites. All the materials display excellent biocompatibility, in vitro, and are successfully: i) molded into medical devices for fracture repair, and ii) used as bone adhesive for fracture fixation and as tooth fillers with the outstanding bond strength that outperform methacrylate systems used today in dental restoration application. Collectively, a new era of advanced TYC materials is unfolded that can fulfill the preconditions as bone fixating implants and for tooth restorations.
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| 6. |
- Asem, Heba, 1987-, et al.
(författare)
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Functional nano-carriers for drug delivery by surface engineering of polymeric nanoparticles post-PISA
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Engineered polymeric nanoparticles (NPs) have been comprehensively explored as potential platforms for diagnosis and targeted therapy for several diseases including cancer. Herein, we designed functional poly(acrylic acid)-b-poly(butyl acrylate) (PAA-b-PBA) NPs using reversible addition-fragmentation chain-transfer (RAFT)-mediated emulsion polymerization via polymerization-induced self-assembly (PISA). The hydrophilic PAA-macroRAFT, forming a stabilizing shell (i.e. corona), was chain-extended using the hydrophobic monomer n-butyl acrylate (n-BA), resulting in stable, monodisperse and reproducible PAA-b-PBA NPs, typically having a diameter of 130 nm. Two approaches of surface engineering of the PAA-b-PBA NPs post-PISA were explored; a two-step and a one-step approach. In the two-step approach, the hydrophilic NP-shell corona was modified with allyl-groups under mild conditions using allylamine in water which resulted in stable allyl-functional NPs (allyl-NPs) suitable for further bio-conjugation. Their versatility was investigated by the subsequent conjugation of a thiol-functional fluorescent dye (BODIPY-SH) to the allyl-groups using click chemistry, in order to mimic the attachment of a thiol-functional target ligand. The average size and size distribution of the corresponding NPs did not change after BODIPY-conjugation. Neither the NPs nor allyl-NPs showed significant cytotoxicity towards RAW264.7 or MCF-7 cell lines, which indicates their desirable safety profile. A one-step approach to concurrently conjugate allyl-groups and a fluorescent dye (FITC) to the preformed PAA-b-PBA NPs was investigated. The cellular uptake of the FITC-NPs using J774A cells in vitro was found to be time- and concentration-dependent. The anti-cancer drug, doxorubicin, was efficiently (90%) encapsulated into the PAA-b-PBA NPs during NP formation. After a small burst release during the first two hours, a controlled release pattern over 7 days was observed. The present investigation demonstrates a potential method to functionalize polymeric NPs post-PISA to produce targeted drug delivery carriers.
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| 7. |
- Di Bucchianico, S., et al.
(författare)
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Genotoxicity of TiO2 nanoparticles assessed by mini-gel comet assay and micronucleus scoring with flow cytometry
- 2017
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Ingår i: Mutagenesis. - : Oxford University Press. - 0267-8357 .- 1464-3804. ; 32:1, s. 127-137
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Tidskriftsartikel (refereegranskat)abstract
- The widespread production and use of nanoparticles calls for faster and more reliable methods to assess their safety. The main aim of this study was to investigate the genotoxicity of three reference TiO2 nanomaterials (NM) within the frame of the FP7-NANoREG project, with a particular focus on testing the applicability of mini-gel comet assay and micronucleus (MN) scoring by flow cytometry. BEAS-2B cells cultured under serum-free conditions were exposed to NM100 (anatase, 50-150 nm), NM101 (anatase, 5-8 nm) and NM103 (rutile, 20-28 nm) for 3, 24 or 48 h mainly at concentrations 1-30 μg/ml. In the mini-gel comet assay (eight gels per slide), we included analysis of (i) DNA strand breaks, (ii) oxidised bases (Fpg-sensitive sites) and (iii) light-induced DNA damage due to photocatalytic activity. Furthermore, MN assays were used and we compared the results of more high-throughput MN scoring with flow cytometry to that of cytokinesis-block MN cytome assay scored manually using a microscope. Various methods were used to assess cytotoxic effects and the results showed in general no or low effects at the doses tested. A weak genotoxic effect of the tested TiO2 materials was observed with an induction of oxidised bases for all three materials of which NM100 was the most potent. When the comet slides were briefly exposed to lab light, a clear induction of DNA strand breaks was observed for the anatase materials, but not for the rutile. This highlights the risk of false positives when testing photocatalytically active materials if light is not properly avoided. A slight increase in MN formation for NM103 was observed in the different MN assays at the lower doses tested (1 and 5 μg/ml). We conclude that mini-gel comet assay and MN scoring using flow cytometry successfully can be used to efficiently study cytotoxic and genotoxic properties of nanoparticles.
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| 8. |
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| 9. |
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| 10. |
- Fan, Yanmiao, et al.
(författare)
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Dendritic Hydrogels Induce Immune Modulation in Human Keratinocytes and Effectively Eradicate Bacterial Pathogens
- 2021
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 143:41, s. 17180-17190
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Tidskriftsartikel (refereegranskat)abstract
- Infections caused by antibiotic-resistant bacteria are globally a major threat, leading to high mortality rates and increased economic burden. Novel treatment strategies are therefore urgently needed by healthcare providers to protect people. Biomaterials that have inherent antibacterial properties and do not require the use of antibiotics present an attractive and feasible avenue to achieve this goal. Herein, we demonstrate the effect of a new class of cationic hydrogels based on amino-functional hyperbranched dendritic-linear-dendritic copolymers (HBDLDs) exhibiting excellent antimicrobial activity toward a wide range of clinical Gram-positive and Gram-negative bacteria, including drug-resistant strains isolated from wounds. Intriguingly, the hydrogels can induce the expression of the antimicrobial peptides RNase 7 and psoriasin, promoting host-mediated bacterial killing in human keratinocytes (HaCaT). Moreover, treatment with the hydrogels decreased the proinflammatory cytokine IL-1 beta, reactive nitrogen species (NO), and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells, conjunctively resulting in reduced inflammation.
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| 11. |
- Fan, Yanmiao, et al.
(författare)
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Nanogel encapsulated hydrogels as advanced wound dressings for the controlled delivery of antibiotics
- 2021
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Ingår i: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Biocompatible and degradable dual-delivery gel systems based on hyperbrancheddendritic−linear−dendritic copolymers (HBDLDs) is herein conceptualizedand accomplished via thiol-ene click chemistry. The elasticity of thehydrogels is tunable by varying the lengths of PEG (2, 6, 10 kDa) or the dryweight percentages (20, 30, 40 wt%), and are found to be between 2–14.7 kPa,comparable to human skin. The co-delivery of antibiotics is achieved, wherethe hydrophilic drug novobiocin sodium salt (NB) is entrapped within thehydrophilic hydrogel, while the hydrophobic antibiotic ciprofloxacin (CIP) isencapsulated within the dendritic nanogels (DNGs) with hydrophobic cores(DNGs-CIP). The DNGs-CIP with drug loading capacity of 2.83 wt% are thenphysically entrapped within the hybrid hydrogels through UV curing. Thehybrid hydrogels enabled the quick release of NB and prolonged released ofCIP. In vitro cell infection assays showed that the antibiotic-loaded hybridhydrogels are able to treat bacterial infections with significant bacterialreduction. Hybrid hydrogel band aids are fabricated and exhibited betterantibacterial activity compared with commercial antimicrobial band aids.Remarkably, most hydrogels and hybrid hydrogels showed enhanced humandermal cell proliferation and could be degraded into non-toxic constituents,showing great promise as wound dressing materials.
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| 12. |
- Fan, Yanmiao, et al.
(författare)
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Scalable Dendritic Hydrogels Targeting Drug-Resistant Skin Pathogens and the Immunomodulation Activity in Keratinocytes
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Microbial infections caused by antibiotic-resistant bacteria are a major threat to humans, associated with a high mortality and for the society increased economic burden. To address this, a series of cationic hydrogels based on amino-functional hyperbranched dendritic−linear−dendritic copolymers (HBDLDs) were formed easily within 1 min through interactions between the amino-terminated HBDLDs and di(N-hydroxysuccinimide ester) functionalized polyethylene glycol (PEG). The hydrogels exhibited excellent inherent antimicrobial activity towards a wide range of Gram-positive and Gram-negative clinical bacteria including drug-resistant strains, isolated from wounds. In vitro cell infection assays showed that the hydrogels were able to significantly reduce cell infections caused by different strains, with the highest killing efficacy of 96% towards S. aureus. The hydrogels also inhibited the initiation of E. coli biofilm formation. Remarkably, the hydrogels induced the expression of the antimicrobial peptides, RNase 7 and psoriasin, in keratinocytes (HaCaT) which suggests that the hydrogels are likely able to promote host-mediated bacterial killing. The expression of pro-inflammatory cytokine IL-1β, reactive nitrogen species (NO) and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells were reduced after the treatment with the hydrogels. The hydrogels degraded within 24 h, showing great promise for treating skin infections and reducing inflammation.
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| 13. |
- Fan, Yanmiao, et al.
(författare)
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Self-Assembled Polyester Dendrimer/Cellulose Nanofibril Hydrogels with Extraordinary Antibacterial Activity
- 2020
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Cationic dendrimers are intriguing materials that can be used as antibacterial materials; however, they display significant cytotoxicity towards diverse cell lines at high generations or high doses, which limits their applications in biomedical fields. In order to decrease the cytotoxicity, a series of biocompatible hybrid hydrogels based on cationic dendrimers and carboxylated cellulose nanofibrils were easily synthesized by non-covalent self-assembly under physiological conditions without external stimuli. The cationic dendrimers from generation 2 (G2) to generation 4 (G4) based on trimethylolpronane (TMP) and 2,2-bis (methylol)propionic acid (bis-MPA) were synthesized through fluoride promoted esterification chemistry (FPE chemistry). FTIR was used to show the presence of the cationic dendrimers within the hybrid hydrogels, and the distribution of the cationic dendrimers was even verified using elemental analysis of nitrogen content. The hybrid hydrogels formed from G3 and G4 showed 100% killing efficiency towards Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) with bacterial concentrations ranging from 10(5) CFU/mL to 10(7) CFU/mL. Remarkably, the hybrid hydrogels also showed good biocompatibility most probably due to the incorporation of the biocompatible CNFs that slowed down the release of the cationic dendrimers from the hybrid hydrogels, hence showing great promise as an antibacterial material for biomedical applications.
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| 14. |
- Garcia-Gallego, Sandra, et al.
(författare)
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Synthesis of Heterofunctional Polyester Dendrimers with Internal and External Functionalities as Versatile Multipurpose Platforms
- 2020
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 21:10, s. 4273-4279
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Tidskriftsartikel (refereegranskat)abstract
- Heterofunctional dendrimers with internal and external representations of functionalities are considered as the ultimate dendritic frameworks. This is reflected by their unprecedented scaffolding, such as precise control over the structure, molecular weight, number, and location of different cargos across the whole dendritic skeleton. Consequently, these dendrimers with multipurpose characters are the pinnacle of precision polymers and thereof are highly attractive to the scientific community as they can find use in a great number of cutting-edge applications, especially as discrete unimolecular carriers for therapeutic exploitation. Unfortunately, most established dendrimer families display external functionalities but lack internal scaffolding ability, which leads to inherent limitations to their full potential use as precision carriers. Consequently, here, we embark on a novel synthetic strategy facilitating the introduction of internal functionalization of established dendrimers. As a proof of concept, a new class of internally and externally functionalized multipurpose dendrimers based on the established 2,2-bis(methylol)propionic acid (bis-MPA) was successfully obtained by the elegant and simple design of AB2C monomers, amalgamated from two traditional AB2 monomers. Utilizing fluoride-promoted esterification (FPE), straightforward layer-by-layer divergent growth up to the fourth generation was successful in less than one day of reaction time, with a molecular weight of 15 kDa, and displaying 93 reactive groups divided by 45 internal and 48 external functionalities. The feasibility of postfunctionalization through click reactions is demonstrated, where the fast and effective attachment of drugs, dyes, and PEG chains is achieved, as well as cross-linking into multifunctional hydrogels. The simplicity and versatility of the presented strategy can easily be transferred to generate a myriad of functional materials such as polymers, surfaces, nanoparticles, or biomolecules.
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| 15. |
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| 16. |
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| 17. |
- Granskog, Viktor, et al.
(författare)
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High-Performance Thiol–Ene Composites Unveil a New Era of Adhesives Suited for Bone Repair
- 2018
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Ingår i: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 28:26
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Tidskriftsartikel (refereegranskat)abstract
- The use of adhesives for fracture fixation can revolutionize the surgical procedures toward more personalized bone repairs. However, there are still no commercially available adhesive solutions mainly due to the lack of biocompatibility, poor adhesive strength, or inadequate fixation protocols. Here, a surgically realizable adhesive system capitalizing on visible light thiol–ene coupling chemistry is presented. The adhesives are carefully designed and formulated from a novel class of chemical constituents influenced by dental resin composites and self-etch primers. Validation of the adhesive strength is conducted on wet bone substrates and accomplished via fiber-reinforced adhesive patch (FRAP) methodology. The results unravel, for the first time, on the promise of a thiol–ene adhesive with an unprecedented shear bond strength of 9.0 MPa and that surpasses, by 55%, the commercially available acrylate dental adhesive system Clearfil SE Bond of 5.8 MPa. Preclinical validation of FRAPs on rat femur fracture models details good adhesion to the bone throughout the healing process, and are found biocompatible not giving rise to any inflammatory response. Remarkably, the FRAPs are found to withstand loads up to 70 N for 1000 cycles on porcine metacarpal fractures outperforming clinically used K-wires and match metal plates and screw implants.
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| 18. |
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| 19. |
- Hed, Yvonne, et al.
(författare)
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Side-by-side comparison of dendritic-linear hybrids and their hyperbranched analogs as micellar carriers of chemotherapeutics
- 2013
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Ingår i: Journal of Polymer Science Part A. - : Wiley. - 0887-624X .- 1099-0518. ; 51:19, s. 3992-3996
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Tidskriftsartikel (refereegranskat)abstract
- Amphiphilic block copolymers are successfully synthesized possessing a hydrophobic dendritic component based on the bis-MPA monomer and a hydrophilic linear polyethylene glycol (PEG) component. The hybrids were either conjured in small scale using robust click reactions between perfect dendrons and linear PEG or multigram polycondensation of hyperbranched blocks from PEG. In all cases, the amphiphiles were assembled to micelles, were found nontoxic and successfully loaded with the chemotherapeutic doxorubicin.
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| 20. |
- Huo, Jingwen, et al.
(författare)
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Drivers of fluctuating embodied carbon emissions in international services trade
- 2021
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Ingår i: One Earth. - : ELSEVIER. - 2590-3330 .- 2590-3322. ; 4:9, s. 1322-1332
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Tidskriftsartikel (refereegranskat)abstract
- Service industries are generally considered "green'' because of their marginal direct emissions; however, they account for 65% of the world gross domestic product and over 20% of total global trade in 2019. Here, we quantify the evolution of carbon emissions embodied in services trade from 2010 to 2018 and identify the driving factors of emission change at the global and regional scales. The annual growth rate of embodied emissions exported from the Global South (2.0%) is double that of the Global North (1.0%), with a different trade structure. We further identify three trade patterns of service export in the Global South based on the bilateral trade partnership and annual growth rate. Three kinds of specific emission mitigation policies are proposed based on the characters of services trade and different trade structures between different regions. The results provide quantitative evidence currently lacking and critical to policy decision making.
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| 21. |
- Hutchinson, Daniel, et al.
(författare)
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Highly Customizable Bone Fracture Fixation through the Marriage of Composites and Screws
- 2021
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Ingår i: Advanced Functional Materials. - : John Wiley and Sons Inc. - 1616-301X .- 1616-3028. ; 31:41
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Tidskriftsartikel (refereegranskat)abstract
- Open reduction internal fixation (ORIF) metal plates provide exceptional support for unstable bone fractures; however, they often result in debilitating soft-tissue adhesions and their rigid shape cannot be easily customized by surgeons. In this work, a surgically feasible ORIF methodology, called AdhFix, is developed by combining screws with polymer/hydroxyapatite composites, which are applied and shaped in situ before being rapidly cured on demand via high-energy visible-light-induced thiol–ene coupling chemistry. The method is developed on porcine metacarpals with transverse and multifragmented fractures, resulting in strong and stable fixations with a bending rigidity of 0.28 (0.03) N m2 and a maximum load before break of 220 (15) N. Evaluations on human cadaver hands with proximal phalanx fractures show that AdhFix withstands the forces from finger flexing exercises, while short- and long-term in vivo rat femur fracture models show that AdhFix successfully supports bone healing without degradation, adverse effects, or soft-tissue adhesions. This procedure represents a radical new approach to fracture fixation, which grants surgeons unparalleled customizability and does not result in soft-tissue adhesions. © 2021 The Authors.
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| 22. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 23. |
- Latorre-Sanchez, Alejandro, et al.
(författare)
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Active quinine-based films able to release antimicrobial compounds via melt quaternization at low temperature
- 2018
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Ingår i: Journal of materials chemistry. B. - : ROYAL SOC CHEMISTRY. - 2050-750X .- 2050-7518. ; 6:1, s. 98-104
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Tidskriftsartikel (refereegranskat)abstract
- The fabrication of antibacterial films based on renewable materials (e.g., chitosan) has attracted significant interest in fields such as food packaging, health care and medicine. However, exploiting the antibacterial properties of cinchona alkaloids to design active nanostructured films able to release quinine-based antimicrobial compounds has not been considered previously. Herein, we develop two different routes to produce active quinine-based nanostructured cross-linked films by exploiting the multiple reactive sites of quinine and, specifically, both the nitrogen atom and the vinyl group of the quinuclidine portion of the molecule, as well as their corresponding orthogonal quaternization and thiol-ene coupling reactions. The first synthetic strategy produces stiff and brittle nanostructured quinine-based films of limited utility for practical applications. Conversely, the second approach produces active, flexible and nanostructured quinine-based films (T-g = - 14 degrees C, Young's modulus = 1.3 GPa), which are able to release antimicrobial compounds against E. coli that, remarkably, are noncytotoxic against mouse macrophage and human dermal fibroblast cells. These kinds of active cinchona alkaloid-based coatings are easy to prepare by means of simple, solvent-free, melt quaternization/spreading procedures at a relatively low temperature (120 degrees C), making this second approach one of the most facile reported procedures to date to produce active nanostructured bio-based films.
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| 24. |
- Lundberg, Pontus, et al.
(författare)
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pH-triggered self-assembly of biocompatible histamine-functionalized triblock copolymers
- 2013
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 9:1, s. 82-89
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Tidskriftsartikel (refereegranskat)abstract
- Histamine functionalized poly(allyl glycidyl ether)-b-poly(ethylene glycol)-b-poly(allyl glycidyl ether) (PAGE-PEO-PAGE) triblock copolymers represent a new class of physically cross-linked, pH-responsive hydrogels with significant potential for biomedical applications. These telechelic triblock copolymers exhibited abrupt and reversible hydrogelation above pH 7.0 due to a hydrophilic/hydrophobic transition of the histamine units to form a network of hydrophobic domains bridged by a hydrophilic PEO matrix. These hydrophobic domains displayed improved ordering upon increasing pH and self-assembled into a body centered cubic lattice at pH 8.0, while at lower concentrations formed well-defined micelles. Significantly, all materials were found to be non-toxic when evaluated on three different cell lines and suggests a range of medical and biomedical applications.
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| 25. |
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| 26. |
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| 27. |
- Porsch, Christian, et al.
(författare)
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Disulfide-Functionalized Unimolecular Micelles as Selective Redox-Responsive Nanocarriers
- 2015
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 16:9, s. 2872-2883
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Tidskriftsartikel (refereegranskat)abstract
- Redox-sensitive hyperbranched dendritic-linear polymers (HBDLPs) were prepared and stabilized individually as unimolecular micelles with diameters in the range 25–40 nm. The high molecular weight (500–950 kDa), core–shell amphiphilic structures were synthesized through a combination of self-condensing vinyl copolymerization (SCVCP) and atom transfer radical polymerization (ATRP). Cleavable disulfide bonds were introduced, either in the backbone, or in pendant groups, of the hyperbranched core of the HBDLPs. By triggered reductive degradation, the HBDLPs showed up to a 7-fold decrease in molecular weight, and the extent of degradation was tuned by the amount of incorporated disulfides. The HBDLP with pendant disulfide-linked functionalities in the hyperbranched core was readily postfunctionalized with a hydrophobic dye, as a mimic for a drug. An instant release of the dye was observed as a response to a reductive environment similar to the one present intracellularly. The proposed strategy shows a facile route to highly stable unimolecular micelles, which attractively exhibit redox-responsive degradation and cargo release properties.
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| 28. |
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| 29. |
- Qin, Liguo, et al.
(författare)
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Cellulose nanofibril reinforced functional chitosan biocomposite films
- 2023
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Ingår i: Polymer testing. - : Elsevier BV. - 0142-9418 .- 1873-2348. ; 120, s. 107964-
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Tidskriftsartikel (refereegranskat)abstract
- Recently, chitosan has become attractive due to being biodegradable, biocompatible and renewable. However, the weak mechanical properties of chitosan films limit their large-scale application. In this work, a strategy of blending TEMPO, oxidized CNF (TOCN) and chitosan was developed to fabricate nanocomposite films in order to improve the mechanical properties and maintain biocompatibility. The TOCN/chitosan nanocomposite films exhibited excellent optical transmittance (>85%) and extremely high tensile strength of 235 MPa. The good compatibility of TOCN and chitosan chains, good dispersion of chitosan aggregates and the presence of stiff TOCN crystal domains are the main reasons for getting improved mechanical strength of composite films. The films showed good biocompatible properties based on the cell activity assay results. Furthermore, they were stable in PBS buffer for more than 6 months without significant degradation. The TOCN/chitosan nanocomposite films with these excellent properties could be employed in medical applications.
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| 30. |
- Stenström, Patrik, et al.
(författare)
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Evaluation of amino-functional polyester dendrimers based on Bis-MPA as nonviral vectors for siRNA delivery
- 2018
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 23:8
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we present the first evaluation of cationic dendrimers based on 2,2-bis(methylol)propionic acid (bis-MPA) as nonviral vectors for transfection of short interfering RNA (siRNA) in cell cultures. The study encompassed dendrimers of generation one to four (G1-G4), modified to bear 6-48 amino end-groups, where the G2-G4 proved to be capable of siRNA complexation and protection against RNase-mediated degradation. The dendrimers were nontoxic to astrocytes, glioma (C6), and glioblastoma (U87), while G3 and G4 exhibited concentration dependent toxicity towards primary neurons. The G2 showed no toxicity to primary neurons at any of the tested concentrations. Fluorescence microscopy experiments suggested that the dendrimers are highly efficient at endo-lysosomal escape since fluorescently labeled dendrimers were localized specifically in mitochondria, and diffuse cytosolic distribution of fluorescent siRNA complexed by dendrimers was observed. This is a desired feature for intracellular drug delivery, since the endocytic pathway otherwise transfers the drugs into lysosomes where they can be degraded without reaching their intended target. siRNA-transfection was successful in C6 and U87 cell lines using the G3 and G4 dendrimers followed by a decrease of approximately 20% of target protein p42-MAPK expression.
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| 31. |
- Stenström, Patrik, et al.
(författare)
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Synthesis and in Vitro Evaluation of Monodisperse Amino-Functional Polyester Dendrimers with Rapid Degradability and Antibacterial Properties
- 2017
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 18:12, s. 4323-4330
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Tidskriftsartikel (refereegranskat)abstract
- Amine functional polymers, especially cationically charged, are interesting biomacromolecules for several reasons, including easy cell membrane entrance, their ability to escape endosomes through the proton sponge effect, spontaneous complexation and delivery of drugs and siRNA, and simple functionalization in aqueous solutions. Dendrimers, a subclass of precision polymers, are monodisperse and exhibit a large and exact number of peripheral end groups in relation to their size and have shown promise in drug delivery, biomedical imaging and as antiviral agents. In this work, hydroxyl functional dendrimers of generation 1 to 5 based on 2,2-bis(methylol)propionic acid (bis-MPA) were modified to bear 6 to 96 peripheral amino groups through esterification reactions with beta-alanine. All dendrimers were isolated in high yields and with remarkable monodispersity. This was successfully accomplished utilizing the present advantages of fluoride-promoted esterification (FPE) with imidazole-activated monomers. Straightforward postfunctionalization was conducted on a second generation amino functional dendrimer with tetraethylene glycol through NHS-amidation and carbonyl diimidazole (CDI) activation to full conversion with short reaction times. Fast biodegradation of the dendrimers through loss of peripheral beta-alanine groups was observed and generational- and dose-dependent cytotoxicity was evaluated with a set of cell lines. An increase. in neurotoxicity compared to hydroxyl-functional dendrimers was shown in neuronal cells, however, the dendrimers were slightly less neurotoxic than commercially available poly(amidoamine) dendrimers (PAMAMs). Additionally, their effect on bacteria was evaluated and the second generation dendrimer was found unique inhibiting the growth of Escherichia coli at physiological conditions while being nontoxic toward human cells. Finally, these results cement a robust and sustainable synthetic route to amino-functional polyester dendrimers with interesting chemical and biological properties.
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| 32. |
- Stenström, Patrik, et al.
(författare)
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UV-Cured Antibacterial Hydrogels Based on PEG and Monodisperse Heterofunctional Bis-MPA Dendrimers
- 2021
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 26:8, s. 2364-
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial infections are one of the major threats to human health due to the raising crisis of antibiotic resistance. Herein, second generation antibacterial heterofunctional dendrimers based on 2,2-bis(methylol)propionic acid were synthesized. The dendrimers possessed six alkenes and 12 ammonium end-groups per molecule and were used to fabricate antibacterial hydrogels together with dithiol-functional polyethylene glycol (mol wt of 2, 6 and 10 kDa) as crosslinkers via thiol-ene chemistry. The network formation can be completed within 10 s upon UV-irradiation as determined by the stabilization of the storage modulus in a rheometer. The hydrogels swelled in aqueous media and could be functionalized with the N-hydroxysuccinimide ester of the dye disperse red 13, which allowed for visually studying the degradation of the hydrogels through the hydrolysis of the ester bonds of the dendritic component. The maximum swelling ratio of the gels was recorded within 4–8 h and the swelling ratios increased with higher molecular weight of the polyethylene glycol crosslinker. The gel formed with 10 kDa polyethylene glycol crosslinker showed the highest swelling ratio of 40 and good mechanical properties, with a storage modulus of 8 kPa. In addition, the hydrogels exhibited good biocompatibility towards both human fibroblasts and mouse monocytes, while showing strong antibacterial activity against both gram-positive and gram-negative bacteria.
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| 33. |
- Sun, Wenjun, et al.
(författare)
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Injectable nano-structured silicon-containing hydroxyapatite microspheres with enhanced osteogenic differentiation and angiogenic factor expression
- 2018
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Ingår i: Ceramics International. - : Elsevier BV. - 0272-8842 .- 1873-3956. ; 44:16, s. 20457-20464
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Tidskriftsartikel (refereegranskat)abstract
- Injectable bioactive ceramics with excellent osteogenesis play important roles in bone regeneration field. In this study, we creatively fabricated the injectable nano-structured silicon-containing hydroxyapatite (Si-HAp) microspheres in diameter of 70–100 µm via hydrothermal treatment of calcium silicate (CaSiO3) microspheres in Na3PO4 aqueous solution. The fabricated Si-HAp microspheres were constructed by nano-rods with a diameter of 100 nm and length up to 1.5 µm. Comparing with the pure HAp microspheres, the obtained nano-structured Si-HAp microspheres exhibited excellent protein loading properties and sustained protein release capacities. Most importantly, the Si-substitution could apparently enhance the proliferation, osteogenic differentiation and the genes expression of angiogenic factors of rat bone marrow mesenchymal stem cells (rBMSCs). These all indicated that the nano-structured Si-HAp microspheres fabricated via hydrothermal transformation method might be used as promising injectable bioactive biomaterials and drug deliveries for bone regeneration.
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| 34. |
- Wang, Deyu, et al.
(författare)
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Memristor-Based In-Circuit Computation for Trace-Based STDP
- 2022
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Ingår i: 2022 Ieee International Conference On Artificial Intelligence Circuits And Systems (Aicas 2022). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 1-4
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Konferensbidrag (refereegranskat)abstract
- Recently, memristors have been widely used to implement Spiking Neural Networks (SNNs), which is promising in edge computing scenarios. However, most memristor-based SNN implementations adopt simplified spike-timing-dependent plasticity (STDP) for the online learning process. It is challenging for memristor-based implementations to support the trace-based STDP learning rules that have been widely used in neuromorphic applications. This paper proposed a versatile memristor-based architecture to implement the synaptic-level trace-based STDP learning rules. Especially, the similarity between synaptic trace dynamics and the memristor nonlinearity is explored and exploited to emulate the trace variables of trace-based STDP. As two typical trace-based STDP learning rules, the pairwise STDP and the triplet STDP, are simulated on two typical nonlinear bipolar memristor devices. The simulation results show that the behavior of physical memristor devices can be well estimated (below 6% in terms of the relative root-mean-square error), and the memristor-based in-circuit computation for trace-based STDP learning rules can achieve a high correlation coefficient over 98%.
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| 35. |
- Wu, Gaochan, et al.
(författare)
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Overview of Recent Strategic Advances in Medicinal Chemistry
- 2019
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 62:21, s. 9375-9414
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Tidskriftsartikel (refereegranskat)abstract
- Introducing novel strategies, concepts, and technologies that speed up drug discovery and the drug development cycle is of great importance both in the highly competitive pharmaceutical industry as well as in academia. This Perspective aims to present a "big-picture" overview of recent strategic innovations in medicinal chemistry and drug discovery.
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| 36. |
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| 37. |
- Wu, Zhihua, et al.
(författare)
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Linear-Dendritic Polymeric Amphiphiles as Carriers of Doxorubicin-In Vitro Evaluation of Biocompatibility and Drug Delivery
- 2012
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Ingår i: Journal of Polymer Science Part A. - : Wiley-Blackwell. - 0887-624X .- 1099-0518. ; 50:2, s. 217-226
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Tidskriftsartikel (refereegranskat)abstract
- In our recent work, we have explored the formation of chemotherapeutic delivery vehicles constructed from four different amphiphilic linear-dendritic hybrid block copolymers. These micelles were found to form about 100-nm-sized structures that were capable of sequestering doxorubicin at loading efficiencies up to 22%. Here, the cellular toxicity of these biocompatible and biodegradable linear-dendritic hybrid materials was evaluated on two breast cancer cell lines and primary human macrophages. The micelles were found not to affect the cellular viability at concentrations below 35 mu g mL(-1). After drug loading, these constructs could deliver an efficient dose of drugs, resulting in significant decreases in cell viability. Kinetic studies indicated that the drug formulation in the poly-mer micelles slowed down the cell uptake compared with the nonformulated drug, but similar efficacy in viability reduction and cell apoptosis were found. Taken together, these linear-dendritic hybrid materials represent an interesting novel architecture for the construction of drug delivery systems. (C) 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 50: 217-226, 2012
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| 38. |
- Xiong, Shaobing, et al.
(författare)
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Revealing buried heterointerface energetics towards highly efficient perovskite solar cells
- 2023
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Ingår i: Nano Energy. - : ELSEVIER. - 2211-2855 .- 2211-3282. ; 109
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Tidskriftsartikel (refereegranskat)abstract
- The heterointerfaces of charge-selective contacts are crucial in determining efficiency and stability of perovskite optoelectronic devices, where the fundamental knowledge of the buried heterointerface between perovskite and bottom charge transport layer is less well understood compared to the top interface. Herein, we systematically investigate the energetics at the perovskite/SnO2 buried heterointerface for an n-i-p perovskite solar cell (PSC) and the perovskite/PEDOT:PSS buried heterointerface for a p-i-n one, respectively. In contrast to previous cognitions, we discover a perovskite transition phase at the buried interface region that originates from the chemical bonding interaction with the bottom charge transport layer. The transition phase causes an energy level barrier and induces defects, impeding charge transport across the heterointerface. These detrimental effects trigger significant nonradiative recombination and limit the attainable device photovoltage. We then develop the energetic models that describe such buried heterointerfaces. Moreover, we further test the proposed model -derived mechanisms via inserting a thin polyvinyl alcohol layer into the buried heterointerfaces of the de-vices. We demonstrate that chemical interactions and formation of the perovskite transition phase at the buried heterointerface thereby are fully restrained, leading to a diminished electron extraction barrier and improved charge transport. As a result, significant increases in open-circuit voltage and fill factor of the devices are ach-ieved. These results will help guide future efforts on developing suitable buried heterointerfaces for superior performance of perovskite optoelectronics.
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| 39. |
- Zeng, Xianghui, et al.
(författare)
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Hyperbranched Copolymer Micelles as Delivery Vehicles of Doxorubicin in Breast Cancer Cells
- 2012
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Ingår i: Journal of Polymer Science Part A. - : Wiley-Blackwell. - 0887-624X .- 1099-0518. ; 50:2, s. 280-288
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Tidskriftsartikel (refereegranskat)abstract
- Four types of drug nanoparticles (NPs) based on amphiphilic hyperbranched block copolymers were developed for the delivery of the chemotherapeutic doxorubicin (DOX) to breast cancer cells. These carriers have their hydrophobic interior layer composed of the hyperbranched aliphatic polyester, Boltorn (R) H30 or Boltorn (R) H40, that are polymers of poly 2,2-bis (methylol) propionic acid (bis-MPA), while the outer hydrophilic shell was composed of about 5 poly(ethylene glycol) (PEG) segments of 5 or 10 kDa molecular weight. A chemotherapeutic drug DOX, was further encapsulated in the interior of these polymer micelles and was shown to exhibit a controlled release profile. Dynamic light scattering and transmission electron microscopy analysis confirmed that the NPs were uniformly sized with a mean hydrodynamic diameter around 110 nm. DOX-loaded H30-PEG10k NPs exhibited controlled release over longer periods of time and greater cytotoxicity compared with the other materials developed against our tested breast cancer cell lines. Additionally, flow cytometry and confocal scanning laser microscopy studies indicated that the cancer cells could internalize the DOX-loaded H30-PEG10k NPs, which contributed to the sustained drug release, and induced more apoptosis than free DOX did. These findings indicate that the H30-PEG10k NPs may offer a very promising approach for delivering drugs to cancer cells. (C) 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 50: 280-288, 2012
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| 40. |
- Zhang, Yuning, et al.
(författare)
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Degradable High Molecular Weight Monodisperse Dendritic Poly(ethylene glycols)
- 2020
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 21:10, s. 4294-4301
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Tidskriftsartikel (refereegranskat)abstract
- Poly(ethylene glycols) (PEGs) are extensively explored by the pharma industry as foundations for new therapeutic products. PEGs are typically used for their conjugation to active drugs, peptides, and proteins and the likeliness to increase the half-life and enhance the therapeutic outcome. Considering the necessity of batch-to-batch consistency for clinical products, monodisperse PEGs are highly attractive but are generally limited to 5 kDa as an upper molecular weight (Mw) and with an oligomer purity of 95%. By amalgamating short, monodisperse PEGs with dendritic frameworks based on 2,2-bis(methylol)propionic acid polyesters, we showcase a robust synthetic approach to monodisperse PEGs with Mw ranging from 2 to 65 kDa. The latter is, to our knowledge, the highest Mw structure of its kind ever reported. Importantly, the dendritic multifunctional connector facilitated degradability at pH 7.4 at 37 °C, which is an important feature for the delivery of therapeutic agents.
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| 41. |
- Zhang, Yuning, et al.
(författare)
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Dendritic Nanogels Directed Dual-Encapsulation Topical Delivery System of Antimicrobial Peptides Targeting Skin Infections
- 2023
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Ingår i: Macromolecular Bioscience. - : John Wiley and Sons Inc. - 1616-5187 .- 1616-5195. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides (AMPs) are promising antibacterial agents in the fight against multidrug resistant pathogens. However, their application to skin infections is limited by the absence of a realizable topical delivery strategy. Herein, a hybrid hierarchical delivery system for topical delivery of AMPs is accomplished through the incorporation of AMPs into dendritic nanogels (DNGs) and their subsequent embedding into poloxamer gel. The high level of control over the crosslink density and the number of chosen functionalities makes DNGs ideal capsules with tunable loading capacity for DPK-060, a human kininogen-derived AMP. Once embedded into the poloxamer gel, DPK-060 encapsulated in DNGs displays a slower release rate compared to those entrapped directly in the gels. In vitro EpiDerm Skin Irritation Tests show good biocompatibility, while MIC and time-kill curves reveal the potency of the peptide toward Staphylococcus aureus. Anti-infection tests on ex vivo pig skin and in vivo mouse infection models demonstrate that formulations with 0.5% and 1% AMPs significantly inhibit the growth of S. aureus. Similar outcomes are observed for an in vivo mouse surgical site infection model. Importantly, when normalizing the bacteria inhibition to released/free DPK-060 at the wound site, all formulations display superior efficacy compared to DPK-060 in solution. © 2023 The Authors.
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| 42. |
- Zhang, Yuning
(författare)
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Development of nanoscale delivery systems for breast cancer treatment
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nanoparticle (NP) assisted diagnosis and drug delivery for antitumor applications have been widely investigated in the past few decades. To date, some of them have been approved for clinical applications and many more of them are under clinical trials. Although some progress has been achieved, it is still necessary to explore novel materials for antitumor applications. The work summarized in this thesis focused on organic NPs, and evaluated engineered polymer NPs and protein-lipid NPs as antitumor drug delivery systems in vitro. And a multifunctional fluorinated NP system was also assessed as theranostic (the combination of therapy and diagnosis) platform. In paper I, two types of 2,2 bis(hydroxymethyl) propionic acid (bis-MPA) based dendritic- linear (DL) polymers were synthesized. One type has the hyperbranched (HB) dendritic structure while the other has dendrons (perfectly branched structures). HBDL and DL materials were compared as drug delivery systems in respect to their synthesis difficulty, quality of micelle formation and efficiency in drug delivery. It was found that HBDL can be synthesized in large scales and drug loaded HBDL tended to have stronger efficacy compared to DL, therefore it is a promising alterative to DL in anticancer drug delivery. Further, in paper II, a detailed study regarding the uptake profile of a bis-MPA based hyperbranched copolymer micelle was conducted. The NP consisted of a Boltorn-H30 core (hyperbranched polyester) and PEG10k hydrophilic tails. It was found that the hyperbranched NP can be internalized into breast cancer cells via clathrin-dependent and macropinocytosis-mediated pathway through a time, concentration and energy dependent process. In paper III, fluorinated copolymers micelles were synthesized and evaluated as theranostic system, which has both diagnostic and therapeutic functions. The consequent micelles were able to load and release doxorubicin (DOX) and demonstrated similar efficacy compared to free (non- formulated) DOX. Also these NPs could generate a detectable signal for 19F-MRI in vitro. In paper IV, unimolecular NPs were developed from polyester based hyperbranched dendritic- linear polymers (HBDLPs). Such micelles were homogenous and did not have critical micelle concentration (CMC). And they were able to load DOX and delivery the drug into breast cancer cells. One HBDLP based NP containing a fluorinated polymer fragment was also synthesized to prove that these unimolecular systems are potentially useful as theranostic platforms. In paper V, histamine functionalized copolymer micelles were developed in order to introduce pH responsive property to NPs and achieve endo-lysosomal escape. These NPs were non-toxic and capable of loading and release DOX. Drug loaded NPs exhibited significant enhanced inhibition of mitochondria function in breast cancer cells during short periods (12 h) compared to free DOX. Although the expected pH responsive behaviour was not observed for the in vitro drug release model, NPs with histamine functionalization demonstrated partly endo-lysosomal escape property, in particular for those with 50% histamine modification. Intracellular tracking of NPs revealed that they could escape from endo-lysosomes and relocate DOX into mitochondria and the nuclei. In paper VI, lipoprotein like NP systems were developed by incorporating Saposin A, phospholipids and selected hydrophobic cargos. Such systems were shown to have promise as drug delivery platforms and to serve as NP based vaccine stabilizers.
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| 43. |
- Zhang, Yuning, et al.
(författare)
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Histamine-functionalized copolymer micelles as a drug delivery system in 2D and 3D models of breast cancer
- 2015
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry (RSC). - 2050-750X .- 2050-7518. ; 3:12, s. 2472-2486
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Tidskriftsartikel (refereegranskat)abstract
- Histamine functionalized block copolymers based on poly(allyl glycidyl ether)-b-poly(ethylene oxide) (PAGE-b-PEO) were prepared with different ratios of histamine and octyl or benzyl groups using UV-initiated thiol-ene click chemistry. At neutral pH, the histamine units are uncharged and hydrophobic, while in acidic environments, such as in the endosome, lysosomes, or extracellular sites of tumours, the histamine groups are positively charged and hydrophilic. pH responsible polymer drug delivery systems is a promising route to site specific delivery of drugs and offers the potential to avoid side effects of systemic treatment. Our detailed in vitro experiments of the efficacy of drug delivery and the intracellular localization characteristics of this library of NPs in 2D and 3D cultures of breast cancer revealed that the 50% histamine-modified polymer loaded with DOX exhibited rapid accumulation in the nucleus of free DOX within 2 h. Confocal studies showed enhanced mitochondrial localization and lysosomal escape when compared to controls. From these combined studies, it was shown that by accurately tuning the structure of the initial block copolymers, the resulting self-assembled NPs can be designed to exploit histamine as an endosomal escape trigger and the octyl/benzyl units give rise to a hydrophobic core resulting in highly efficacious drug delivery systems (DDS) with control over intracellular localization. Optimization and rational control of the intracellular localization of both DDS and the parent drug can give nanomedicines a substantial increase in efficacy and should be explored in future studies.
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| 44. |
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| 45. |
- Zhang, Yuning
(författare)
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Novel Therapeutic Platform of Micelles and Nanogels from Dopa-Functionalized Triblock Copolymers
- 2021
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Ingår i: Small. - : Wiley. - 1613-6829 .- 1613-6810. ; 17:17, s. 2007305-
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Tidskriftsartikel (refereegranskat)abstract
- Multi-drug delivery systems constructed from a basic polymeric scaold, and which have the ability to target a variety of biomedical applications, can streamline the development of nanomedicine to provide both environmental and economical relief. Herein, amphiphilic ABA-triblock copolymers are synthesized and assembled sequentially into micelles and nanogels as drug delivery systems following a thorough evaluation on advanced in vitro models to explore their potential for the treatment of cancer and bacterial infections. Short blocks of -methyl--allyloxycarbonyl-,-dioxan--one (MAC) are oli-gomerized from PEGk and thereafter functionalized with dihydroxyphenyla-lanine (dopa)-functional thiols using thiol-ene coupling (TEC) click chemistry. The copolymers self-assemble into well-defined micelles in aqueous solution and are further formulated into nanogels via UV-induced TEC. The resulting spherical micelles and nanogels are stable nanoparticles, with sizes ranging between and nm. The nanogels are found to be non-toxic to a panel of cell lines and mask the toxicity of the potent drugs until their release. The nanogels would be superior to micelles for the elimination of cancer cells supported by both D cell culture and a D spheroid model. The opposite conclusion could be drawn for bacteria inhibition.
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| 46. |
- Zhang, Yuning, et al.
(författare)
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Off-Stoichiometric Thiol-Ene Chemistry to Dendritic Nanogel Therapeutics
- 2019
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Ingår i: Advanced Functional Materials. - : Wiley-VCH Verlag. - 1616-301X .- 1616-3028. ; 29:18
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Tidskriftsartikel (refereegranskat)abstract
- A novel platform of dendritic nanogels is herein presented, capitalizing on the self-assembly of allyl-functional polyesters based on dendritic-linear-dendritic amphiphiles followed by simple cross-linking with complementary monomeric thiols via UV initiated off-stoichiometric thiol-ene chemistry. The facile approach enabled multigram creation of allyl reactive nanogel precursors, in the size range of 190–295 nm, being readily available for further modifications to display a number of core functionalities while maintaining the size distribution and characteristics of the master batch. The nanogels are evaluated as carriers of a spread of chemotherapeutics by customizing the core to accommodate each individual cargo. The resulting nanogels are biocompatible, displaying diffusion controlled release of cargo, maintained therapeutic efficacy, and decreased cargo toxic side effects. Finally, the nanogels are found to successfully deliver pharmaceuticals into a 3D pancreatic spheroids tumor model.
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| 47. |
- Zheng, Haoquan, et al.
(författare)
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One-pot Synthesis of Metal Organic Frameworks with Encapsulated Target Molecules and Their Applications for Controlled Drug Delivery
- 2016
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 138:3, s. 962-968
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Tidskriftsartikel (refereegranskat)abstract
- Many medical and chemical applications require target molecules to be delivered in a controlled manner at precise locations. Metal-organic frameworks (MOFs) have high porosity, large surface area, and tunable functionality and are promising carriers for such purposes. Current approaches for incorporating target molecules are based on multistep postfunctionalization. Here, we report a novel approach that combines MOF synthesis and molecule encapsulation in a one-pot process. We demonstrate that large drug and dye molecules can be encapsulated in zeolitic imidazolate framework (ZIF) crystals. The molecules are homogeneously distributed within the crystals, and their loadings can be tuned. We show that ZIF-8 crystals loaded with the anticancer drug doxorubicin (DOX) are efficient drug delivery vehicles in cancer therapy using pH-responsive release. Their efficacy on breast cancer cell lines is higher than that of free DOX. Our one-pot process opens new possibilities to construct multifunctional delivery systems for a wide range of applications.
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