| 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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Heterogeneous Rupturing Dendrimers
- 2017
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126.
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Tidskriftsartikel (refereegranskat)abstract
- Utilizing macromolecular scaffolds as templates for the production of small molecules that are distinctively different from the original monomer feedstock has many potential applications. Herein, as a proof-of-concept, a family of dendrimers displaying internally queued disulfide bridges were synthesized and exploited as flawless macromolecular templates that selectively rupture into a set of monomeric mercaptans. Disassembly was accomplished in a reducing environment, using DTT as an external stimulus, and the thiol constituents were successfully isolated. Their composition was dictated by three dendritic regions, i.e., (i) the symmetrical trithiol of the core (C3), (ii) the interior-asymmetric trithiols (CD2), and (iii) the periphery-asymmetric monothiols (DB2), in which B functionality is of an orthogonal nature. Taking into account the steady state between disulfides and thiols in all living cells, the collapse of the dendrimers to a multitude of smaller thiols was intracellularly assessed as a means to disrupt the balance of reactive oxygen species (ROS) often elevated in cancer cells. Indeed, the fragmentation induced a significant increase of ROS in human lung carcinoma A549 cells. These findings can potentially alter the perception of dendrimers being limited to carriers to being prodrugs for intracellular delivery of ROS with the potential to fight cancer.
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| 3. |
- Andrén, Oliver C. J., et al.
(författare)
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Multifunctional Poly(ethylene glycol) : Synthesis, Characterization, and Potential Applications of Dendritic-Linear-Dendritic Block Copolymer Hybrids
- 2013
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Ingår i: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 46:10, s. 3726-3736
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Tidskriftsartikel (refereegranskat)abstract
- Emerging dendritic-linear-dendritic (DLD) hybrids that possess synergetic properties of linear and highly functional branched dendritic polymers are becoming important macromolecular scaffolds in fields ranging from biomedicine to nanotechnology. By exploiting pseudo-one-step polycondensation reactions, a facile and scalable synthetic methodology for the construction of highly functional DLDs has been developed. A library of three sets of DLDs exhibiting a hydrophilic linear PEG core with covalently attached hyperbranched bis-MPA blocks was synthesized up to the seventh generation with 256 reactive peripheral hydroxyl groups. The degree of branching for the hybrids was found between 0.40 and 0.59 with dispersities ranging from 1.03 to 1.88. The introduction of hyperbranched components resulted in control over or even full disruption of the crystallinity of the PEG. Postfunctionalizations of the peripheral hydroxyl groups with azides, allyls, and ATRP initiators yielded reactive intermediates. These intermediates were successfully assessed through UV-initiated thiol-ene coupling reactions for the synthesis of charged hybrids. ATRP of styrene from the pheriphery afforded amphiphilic macromolecules. Finally, their scaffolding capacity was evaluated for the fabrication of 3D networks, i.e, novel dendritic hydrogels and highly ordered breath figures.
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| 4. |
- 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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| 5. |
- Andrén, Oliver, 1987-
(författare)
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Exploring bis-MPA Based Dendritic Structures in Biomedicine
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the last decades there has been significant advances in polymer chemistry. New coupling chemistries, polymerization techniques and accelerated approaches enable researches to push the limits of structural control. One outcome of such development is the field of linear dendritic (LD) and dendritic linear dendritic (DLD) hybrid materials, drawing benefit from both linear and dendritic material properties. LD-hybrids with their high density of functional groups and customizability offer much promise for use in biological applications. This thesis deals with the potential use of sophisticated LD-hybrid materials focusing on the field of biomedicine and biomedical applications. The linear component is manly poly(ethylene glycol) (PEG) while the dendritic part consists of 2,2-Bis(hydroxymethyl)propionic (bis-MPA) building blocks.Initially a family of unsymmetrical LD amphiphiles was constructed and evaluated as carriers for drug delivery of chemotherapeutics. Through self-assembly driven by their amphiphilic nature nanocarriers (NC) were constructed with a hydrophobic core and hydrophilic corona. NC were found to enhance the effect of conventional therapeutics by relocating the drug from just the nucleus to the mitochondria among other organelles. Their versatile nature allowed for dual loading of a combination of chemotherapeutics and circumvented the resistance mechanism of resistant cancer cells.Dendrimers containing a disulfide in the backbone were also constructed, these enabled the selective fragmentation of the dendrimer by reduction to small molecular thiols. The fragments were also envisioned to disrupt the delicate thiol-disulfide balance intracellularly causing reactive oxygen species (ROS). Dendrimers were elaborated by conjugation to linear PEG creating LD-hybrids and evaluated in vitro and where found to cause high degree of ROS in cancerous cells.Thiol functional polymers were created, including linear polymers, dendrimers and DLD-hybrids. The DLD-hybrids were utilized as hydrogels through two efficient chemistries relying on the versatility of the thiol. By varying the generation of the LD-hybrid and the cross-linking chemistry the modulus could be tuned.Amine functional LD-hybrids were constructed utilizing the amino acid alanine. Scaffolds were utilized as antimicrobial hydrogels for prophylaxis during surgical intervention. LD-hybrids were initially evaluated in planktonic mode, and were found to have broad spectrum effect and were highly effective against resistant bacteria. Gelation was studied relying on N-hydroxysuccinimide (NHS) esters as cross-linkers, enabling instantaneous gelation under biological conditions. The gels moduli could be varied to match various tissues including stromal and muscle. The effect of the antimicrobial coatings was investigated with promising results both in vitro and in vivo.Finally, more industrially applicable hyperbranched LD-hybrids were constructed. The synthetic strategy relied on a convenient pseudo one-pot approach using Fisher esterification along with sequential monomer addition. Materials were found to have properties and characteristics similar to those of perfect dendritic LD-hybrids. And the scaffolds were evaluated in a range of applications such as hydrogels and isopourous films with promising results.
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| 6. |
- Andrén, Oliver, et al.
(författare)
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Facile thiolation of hydroxyl functional polymers
- 2017
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Ingår i: Polymer Chemistry. - : Royal Society of Chemistry. - 1759-9954 .- 1759-9962. ; 8:34, s. 4996-5001
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Tidskriftsartikel (refereegranskat)abstract
- Sulfur is an important component in many biological systems. In the hands of an organic chemist it can provide an ample handle for a myriad of robust reactions including thiol-ene click chemistry. However, in polymer chemistry the thiol functionality is rarely attributed to the macromolecule due to unatainable synthetic protocols. Herein, we provide a simple and robust strategy to produce thiol-functional polymers. The chemistry capitalizes on an unsymmetrical disulfide that straightforwardly converts hydroxyl functional polymers to their thiolated counterpart. Finally, PEG hydrogels, using both thiol-ene and Michael addition, is used to showcase the possibilities presented by thiol functional polymers.
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| 7. |
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| 8. |
- Auty, Sam E. R., et al.
(författare)
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One-pot' sequential deprotection/functionalisation of linear-dendritic hybrid polymers using a xanthate mediated thiol/Michael addition
- 2015
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Ingår i: Polymer Chemistry. - : Royal Society of Chemistry (RSC). - 1759-9954 .- 1759-9962. ; 6:4, s. 573-582
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Tidskriftsartikel (refereegranskat)abstract
- Thiol-Michael addition chemistry is a powerful tool for the preparation of functional materials. In this first report of xanthate-functional linear-dendritic polymer hybrids, the preparation of four generations of xanthate-functionalised dendron atom transfer radical polymerisation macroinitiators is described using an orthogonal chemical strategy. The controlled polymerisation of tertiary butyl methacrylate is demonstrated to high conversion and without interference from the xanthate surface groups. Modification of the peripheral xanthate groups of dendrons at the hybrid polymer chain-end has been studied using a one-pot deprotection/functionalisation strategy and a range of commercially available and bespoke acrylate monomers to form complex polymer architectures from feedstock polymers, differing in the number of modified end groups and the surface chemistry of the dendron chain end.
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| 9. |
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| 10. |
- Garcia Gallego, Sandra, et al.
(författare)
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Accelerated Chemoselective Reactions to Sequence-Controlled Heterolayered Dendrimers
- 2020
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126.
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Tidskriftsartikel (refereegranskat)abstract
- Chemoselective reactions are a highly desirable approach to generate well-defined functional macromolecules. Their extraordinary efficiency and selectivity enable the development of flawless structures, such as dendrimers, with unprecedented structure-to-property capacity but with typically tedious synthetic protocols. Here we demonstrate the potency of chemoselective reactions to accomplish sequence-controlled heterolayered dendrimers. An accurate accelerated design of bis-MPA monomers with orthogonally complementary moieties and a wisely selected chemical toolbox generated highly complex monodisperse dendrimers through simplified protocols. The versatility of the strategy was proved by obtaining different dendritic families with different properties after altering the order of addition of the monomers. Moreover, we evaluated the feasibility of the one-pot approach toward these heterolayered dendrimers as proof-of-concept.
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| 11. |
- Granskog, Viktor, et al.
(författare)
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Linear Dendritic Block Copolymers as Promising Biomaterials for the Manufacturing of Soft Tissue Adhesive Patches Using Visible Light Initiated Thiol-Ene Coupling Chemistry
- 2015
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Ingår i: Advanced Functional Materials. - : Wiley-VCH Verlagsgesellschaft. - 1616-301X .- 1616-3028. ; 25:42, s. 6596-6605
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Tidskriftsartikel (refereegranskat)abstract
- A library of dendritic-linear-dendritic (DLD) materials comprising linear poly(ethylene glycol) and hyperbranched dendritic blocks based on 2,2-bis(hydroxymethyl) propionic acid is successfully synthesized and post-functionalized with peripheral allyl groups. Reactive DLDs with pseudo-generations of 3 to 6 (G3-G6) are isolated in large scale allowing their thorough evaluation as important components for the development of biomedical adhesives. Due to their branched nature and inherent degradable ester-bonds, promising biomaterial resins are accomplished with suitable viscosity, eliminating the excessive use of co-solvents. By utilizing benign high-energy visible light initiated thiol-ene coupling chemistry, DLDs together with tris[2-(3-mercaptopropionyloxy) ethyl] isocyanurate and surgical mesh enable the fabrication of soft tissue adhesive patches (STAPs) within a total irradiation time of 30 s. The STAPs display the ability to create good adhesion to wet soft tissue and encouraging results in cytotoxicity tests. All crosslinked materials are also found to degrade after being stored in human blood plasma and phosphate buffered saline. The proposed benign methodology coupled with the promising features of the crosslinked materials is herein envisioned as a soft tissue adhesive with properties that do not exist in currently available tissue adhesives.
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| 12. |
- Hern, Faye Y., et al.
(författare)
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Model studies of the sequential and simultaneous statistical modification of dendritic functional groups and their implications within complex polymer architecture synthesis
- 2017
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Ingår i: Polymer Chemistry. - : Royal Society of Chemistry. - 1759-9954 .- 1759-9962. ; 8:10, s. 1644-1653
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Tidskriftsartikel (refereegranskat)abstract
- Post-synthesis modification of polymers is a synthetically appealing approach to generate a range of samples from a single, well-characterised starting material. When partial or mixed-functionalisation is sought, an inevitable statistical distribution of modification outcomes will lead to considerable variation of chemical structures within the final sample. Here we have comprehensively investigated the postsynthesis sequential/partial and simultaneous mixed modification of xanthate-functional ideal dendrons and used this data to consider the implications for the more complex linear-dendritic hybrids and hyper-branched- polydendron analogues. Although H-1 NMR confirmed the potential to direct the reactions, it was clear from MALDI-TOF studies that very little of the actual targeted structures were generated in the statistical reactions.
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| 13. |
- Hult, Daniel, 1986-, et al.
(författare)
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Degradable High Tg Sugar Derived Polycarbonates from Isosorbide and Dihydroxyacetone
- 2018
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Ingår i: Polymer Chemistry. - : Royal Society of Chemistry. - 1759-9954 .- 1759-9962. ; 9:17, s. 2238-2246
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Tidskriftsartikel (refereegranskat)abstract
- Polycarbonates from isosorbide and dihydroxyacetone (DHA) have been synthesised using organocatalytic step-growth polymerization of their corresponding diols and bis-carbonylimidazolides monomers. By choice of feed ratio and monomer activation, either isosorbide or ketal protected DHA, random and alternating poly(Iso-co-DHA) carbonates have been formed. Thermal properties by DSC and TGA were herein strongly correlated to monomer composition. Dilution studies using 1H-NMR of a model compound DHA-diethyl carbonate in acetonitrile and deuterated water highlighted the influence of α-substituents on the keto/hydrate equilibrium of DHA. Further kinetics studies of in the pH* range of 4.7 to 9.6 serve to show the hydrolytic pH-profile of DHA-carbonates. The Hydrolytic degradation of deprotected polymer pellets show an increased degradation with increasing DHA content. Pellets with a random or alternating configuration show different characteristics in terms of mass loss and molecular weight loss profile over time.
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| 14. |
- Kikionis, Stefanos, et al.
(författare)
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Nanofibrous nonwovens based on dendritic-linear-dendritic poly(ethylene glycol) hybrids
- 2018
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Ingår i: Journal of Applied Polymer Science. - : John Wiley & Sons. - 0021-8995 .- 1097-4628. ; 135:10
-
Tidskriftsartikel (refereegranskat)abstract
- Dendritic-linear-dendritic (DLD) hybrids are highly functional materials combining the properties of linear and dendritic polymers. Attempts to electrospin DLD polymers composed of hyperbranched dendritic blocks of 2,2-bis(hydroxymethyl) propionic acid on a linear poly(ethylene glycol) core proved unsuccessful. Nevertheless, when these DLD hybrids were blended with an array of different biodegradable polymers as entanglement enhancers, nanofibrous nonwovens were successfully prepared by electrospinning. The pseudogeneration degree of the DLDs, the nature of the co-electrospun polymer and the solvent systems used for the preparation of the electrospinning solutions exerted a significant effect on the diameter and morphology of the electrospun fibers. It is worth-noting that aqueous solutions of the DLD polymers and only 1% (w/v) poly(ethylene oxide) resulted in the production of smoother and thinner nanofibers. Such dendritic nanofibrous scaffolds can be promising materials for biomedical applications due to their bio-compatibility, biodegradability, multifunctionality, and advanced structural architecture.
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| 15. |
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| 16. |
- Martin-Serrano Ortiz, Angela, et al.
(författare)
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Design of multivalent fluorescent dendritic probes for site-specific labeling of biomolecules
- 2018
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Ingår i: Journal of Polymer Science Part A. - : WILEY. - 0887-624X .- 1099-0518. ; 56:15, s. 1609-1616
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Tidskriftsartikel (refereegranskat)abstract
- Herein, the synthesis and characterization of orthogonal dendrons decorated with multiple units of fluorescent and a chemoselective group at a focal point, followed by specific antibody labeling, is presented. Fluorescence results confirm the applicability of the fluorescent probes for biomolecule labeling and fluorescent signal amplification.
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| 17. |
- Mongkhontreerat, Surinthra, et al.
(författare)
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Beyond state of the art honeycomb membranes : High performance ordered arrays from multi-programmable linear-dendritic block copolymers
- 2015
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Ingår i: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 25:30
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Tidskriftsartikel (refereegranskat)abstract
- A new generation of honeycomb membranes is herein described from a novel library of multipurpose linear-dendritic block copolymers. These are accomplished by combining atom transfer radical polymerization together with dendrimer chemistry and click reactions. The resulted amorphous block copolymers, with T-g between 30 and 40 degrees C, display three important functions, i.e., pore generating aromatic groups, crosslinking azides, and multiple dendritic functional groups. All block copolymers enable the successful fabrication of honeycomb membranes through the facile breath figure method. The peripheral dendritic functionality is found to influence the porous morphologies from closed pored structure with pore size of 1.12 mu m(2) to open pore structure with pore size 10.26 mu m(2). Facile UV crosslinking of the azides yields membranes with highly durable structural integrity. Upon crosslinking, the pH and thermal stability are extended beyond the noncrosslinked membranes in which the porous integrity is maintained up to 400 degrees C and pH 1-14. Taking into account the straightforward and cost-efficient strategy to generate ordered, functional, and structurally stable honeycomb membranes on various solid substrates, it is apparent that these multipurpose block copolymers may unlock future applications including use as molds for soft lithography.
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| 18. |
- Mongkhontreerat, Surinthra, et al.
(författare)
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Dendritic hydrogels : From exploring various crosslinking chemistries to introducing functions and naturally abundant resources
- 2015
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Ingår i: Journal of Polymer Science Part A. - : Wiley. - 0887-624X .- 1099-0518. ; 53:21, s. 2431-2439
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic hydrogels from dendritic-linear-dendritic (DLD) block copolymers based on PEG and bis-MPA dendrons were constructed via UV-initiated thiol-ene, thiol-yne, CuAAC, and amine-NHS crosslinking chemistries. Stoichiometric ratio manipulations, prior to film formation, resulted in functional hydrogels with tuneable compressive moduli. The highest gel fractions for all networks were obtained at off-stoichiometric ratios with surplus of DLDs. Finally, sustainable networks were fabricated by amalgamating DLD, naturally abundant cellulose nanocrystal, and protein-based bovine serum albumin.
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| 19. |
- Nordström, Randi, 1986-, et al.
(författare)
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Degradable dendritic nanogels as carriers for antimicrobial peptides
- 2019
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 554, s. 592-602
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we investigate degradable anionic dendritic nanogels (DNG) as carriers for antimicrobial peptides (AMPs). In such systems, the dendritic part contains carboxylic acid-based anionic binding sites for cationic AMPs, whereas linear poly(ethylene glycol) (PEG) chains form a shell for promotion of biological stealth. In order to clarify factors influencing membrane interactions of such systems, we here address effects of nanogel charge, cross-linking, and degradation on peptide loading/release, as well as consequences of these factors for lipid membrane interactions and antimicrobial effects. The DNGs were found to bind the AMPs LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) and DPK-060 (GKHKNKGKKNGKHNGWKWWW). For the smaller DPK-060 peptide, loading was found to increase with increasing nanogel charge density. For the larger LL-37, on the other hand, peptide loading was largely insensitive to nanogel charge density. In line with this, results on the secondary structure, as well as on the absence of stabilization from proteolytic degradation by the nanogels, show that the larger LL-37 is unable to enter into the interior of the nanogels. While 40–60% nanogel degradation occurred over 10 days, promoted at high ionic strength and lower cross-linking density/higher anionic charge content, peptide release at physiological ionic strength was substantially faster, and membrane destabilization not relying on nanogel degradation. Ellipsometry and liposome leakage experiments showed both free peptide and peptide/DNG complexes to cause membrane destabilization, indicated also by antimicrobial activities being comparable for nanogel-bound and free peptide. Finally, the DNGs were demonstrated to display low toxicity towards erythrocytes even at peptide concentrations of 100 µM.
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| 20. |
- Nordström, Randi, et al.
(författare)
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Membrane interactions of microgels as carriers of antimicrobial peptides
- 2018
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Ingår i: Journal of Colloid and Interface Science. - : Academic Press Inc.. - 0021-9797 .- 1095-7103. ; 513, s. 141-150
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Tidskriftsartikel (refereegranskat)abstract
- Microgels are interesting as potential delivery systems for antimicrobial peptides. In order to elucidate membrane interactions of such systems, we here investigate effects of microgel charge density on antimicrobial peptide loading and release, as well as consequences of this for membrane interactions and antimicrobial effects, using ellipsometry, circular dichroism spectroscopy, nanoparticle tracking analysis, dynamic light scattering and z-potential measurements. Anionic poly(ethyl acrylate-co-methacrylic acid) microgels were found to incorporate considerable amounts of the cationic antimicrobial peptides LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) and DPK-060 (GKHKNKGKKNGKHNGWKWWW) and to protect incorporated peptides from degradation by infection-related proteases at high microgel charge density. As a result of their net negative z-potential also at high peptide loading, neither empty nor peptide-loaded microgels adsorb at supported bacteria-mimicking membranes. Instead, membrane disruption is mediated almost exclusively by peptide release. Mirroring this, antimicrobial effects against several clinically relevant bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Pseudomonas aeruginosa) were found to be promoted by factors facilitating peptide release, such as decreasing peptide length and decreasing microgel charge density. Microgels were further demonstrated to display low toxicity towards erythrocytes. Taken together, the results demonstrate some interesting opportunities for the use of microgels as delivery systems for antimicrobial peptides, but also highlight several key factors which need to be controlled for their successful use.
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| 21. |
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| 22. |
- Olofsson, Kristina, et al.
(författare)
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Recent Advances on Crosslinked Dendritic Networks
- 2014
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Ingår i: Journal of Applied Polymer Science. - : Wiley. - 0021-8995 .- 1097-4628. ; 131:3, s. 39876-
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Forskningsöversikt (refereegranskat)abstract
- The branched architectures of dendritic polymers display a large number of end groups, and dendrimers have been extensively evaluated as scaffolds in a large array of research fields, including biomedicine and nanotechnology. From the number of potential applications that require advanced crosslinked films, dendritic macromolecules are attractive as scaffolds that deliver on promising crosslinked three-dimensional (3D) networks. This review briefly covers a description of the family of functional dendritic polymers, ranging from dendrimers and dendrons to hyperbranched polymers and dendritic linear hybrids. The review also contains a detailed report on proposed chemistries for the exploitation of dendritic materials as scaffolds in the field of advanced networks.
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| 23. |
- Rozenbaum, Rene T., et al.
(författare)
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Penetration and Accumulation of Dendrons with Different Peripheral Composition in Pseudomonas aeruginosa Biofilms
- 2019
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Ingår i: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 19:7, s. 4327-4333
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Tidskriftsartikel (refereegranskat)abstract
- Multidrug resistant bacterial infections threaten to become the number one cause of death by the year 2050. Development of antimicrobial dendritic polymers is considered promising as an alternative infection control strategy. For antimicrobial dendritic polymers to effectively kill bacteria residing in infectious biofilms, they have to penetrate and accumulate deep into biofilms. Biofilms are often recalcitrant to antimicrobial penetration and accumulation. Therefore, this work aims to determine the role of compact dendrons with different peripheral composition in their penetration into Pseudomonas aeruginosa biofilms. Red fluorescently labeled dendrons with pH-responsive NH3+ peripheral groups initially penetrated faster from a buffer suspension at pH 7.0 into the acidic environment of P. aeruginosa biofilms than dendrons with OH or COO- groups at their periphery. In addition, dendrons with NH3+ peripheral groups accumulated near the top of the biofilm due to electrostatic double-layer attraction with negatively charged biofilm components. However, accumulation of dendrons with OH and COO- peripheral groups was more evenly distributed across the depth of the biofilms than NH3+ composed dendrons and exceeded accumulation of NH3+ composed dendrons after 10 min of exposure. Unlike dendrons with NH3+ groups at their periphery, dendrons with OH or COO- peripheral groups, lacking strong electrostatic double-layer attraction with biofilm components, were largely washed-out during exposure to PBS without dendrons. Thus, penetration and accumulation of dendrons into biofilms is controlled by their peripheral composition through electrostatic double-layer interactions, which is an important finding for the further development of new antimicrobial or antimicrobial-carrying dendritic polymers.
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| 24. |
- Stenström, Patrik, et al.
(författare)
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Fluoride-promoted esterification (FPE) chemistry : A robust route to Bis-MPA dendrons and their postfunctionalization
- 2016
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 21:3
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Tidskriftsartikel (refereegranskat)abstract
- Bifunctional dendrons based on 2,2-bis(methylol)propionic acid (bis-MPA) are highly desirable scaffolds for biomedical applications. This is due to their flawless nature and large and exact number of functional groups as well as being biodegradable and biocompatible. Herein, we describe a facile divergent growth approach to their synthesis from monobenzylated tetraethylene glycol and post functionalization utilizing fluoride-promoted esterification (FPE) chemistry protocols. The scaffolds, presenting selectively deprotectable hydroxyls in the periphery and at the focal point, were isolated on a multigram scale with excellent purity up to the fourth generation dendron with a molecular weight of 2346 Da in seven reactions with a total yield of 50%. The third generation dendron was used as a model compound to demonstrate its functionalizability. Selective deprotection of the dendron's focal point was achieved with an outstanding yield of 94%, and biotin as well as azido functionalities were introduced to its focal point and periphery, respectively, through FPE chemistry. Bulky disperse red dyes were clicked through CuAAC to the dendron's azido groups, giving a biotinylated dendron with multivalent dyes with a molecular weight of 6252 Da in a total yield of 37% in five reactions with an average yield of 82% starting from the third generation focally and peripherally protected dendron. FPE chemistry proved to be a superb improvement over previous protocols towards bis-MPA dendrons as high purity and yields were obtained with less toxic solvents and greatly improved monomer utilization.
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| 25. |
- 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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| 26. |
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| 27. |
- 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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| 28. |
- 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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| 29. |
- 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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| 30. |
- 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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