| 1. |
- Abdel Aziz, Ilaria, et al.
(författare)
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Drug delivery via a 3D electro-swellable conjugated polymer hydrogel
- 2024
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Ingår i: Journal of materials chemistry. B. - : ROYAL SOC CHEMISTRY. - 2050-750X .- 2050-7518.
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Tidskriftsartikel (refereegranskat)abstract
- Spatiotemporal controlled drug delivery minimizes side-effects and enables therapies that require specific dosing patterns. Conjugated polymers (CP) can be used for electrically controlled drug delivery; however so far, most demonstrations were limited to molecules up to 500 Da. Larger molecules could be incorporated only during the CP polymerization and thus limited to a single delivery. This work harnesses the record volume changes of a glycolated polythiophene p(g3T2) for controlled drug delivery. p(g3T2) undergoes reversible volumetric changes of up to 300% during electrochemical doping, forming pores in the nm-size range, resulting in a conducting hydrogel. p(g3T2)-coated 3D carbon sponges enable controlled loading and release of molecules spanning molecular weights of 800-6000 Da, from simple dyes up to the hormone insulin. Molecules are loaded as a combination of electrostatic interactions with the charged polymer backbone and physical entrapment in the porous matrix. Smaller molecules leak out of the polymer while larger ones could not be loaded effectively. Finally, this work shows the temporally patterned release of molecules with molecular weight of 1300 Da and multiple reloading and release cycles without affecting the on/off ratio.
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| 2. |
- Adler, Anna, et al.
(författare)
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Effect of liposome surface modification with water-soluble phospholipid polymer chain-conjugated lipids on interaction with human plasma proteins
- 2022
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry. - 2050-750X .- 2050-7518. ; 10:14, s. 2512-2522
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Tidskriftsartikel (refereegranskat)abstract
- Alternative liposome surface coatings for PEGylation to evade the immune system, particularly the complement system, have garnered significant interest. We previously reported poly(2-methacryloyloxyethyl phosphorylcholine) (MPC)-based lipids (PMPC-lipids) and investigated the surface modification of liposomes. In this study, we synthesize PMPC-lipids with polymerization degrees of 10 (MPC10-lipid), 20 (MPC20-lipid), 50 (MPC50-lipid), and 100 (MPC100-lipid), and coated liposomes with 1, 5, or 10 mol% PMPC-lipids (PMPC-liposomes). Non-modified and PEGylated liposomes are used as controls. We investigate the liposome size, surface charge, polydispersity index, and adsorption of plasma proteins to the liposomes post incubation in human plasma containing N,N,N′,N′-ethylenediamine tetraacetic acid (EDTA) or lepirudin by some methods such as sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), western blotting, and automated capillary western blot, with emphasis on the binding of complement protein C3. It is shown that the coating of liposome PMPC-lipids can suppress protein adsorption more effectively with an increase in the molecular weight and molar ratio (1-10 mol%). Apolipoprotein A-I is detected on PMPC-liposomes with a higher molecular weight and higher molar ratio of PMPC-lipids, whereas α2-macroglobulin is detected on non-modified, PEGylated, and PMPC-liposomes with a shorter polymer chain. In addition, a correlation is shown among the PMPC molecular weight, molar ratio, and C3 binding. The MPC10-lipid cannot inhibit C3 binding efficiently, whereas surface modifications with 10 mol% MPC20-lipid and 5 mol% and 10 mol% MPC50-lipid suppress both total protein and C3 binding. Hence, liposome modification with PMPC-lipids can be a possible strategy for avoiding complement activation.
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| 3. |
- Adler, Anna, et al.
(författare)
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Effect of liposome surface modification with water-soluble phospholipid polymer chain-conjugated lipids on interaction with human plasma proteins
- 2022
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry (RSC). - 2050-750X .- 2050-7518. ; 10:14, s. 2512-2522
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Tidskriftsartikel (refereegranskat)abstract
- Alternative liposome surface coatings for PEGylation to evade the immune system, particularly the complement system, have garnered significant interest. We previously reported poly(2-methacryloyloxyethyl phosphorylcholine) (MPC)-based lipids (PMPC-lipids) and investigated the surface modification of liposomes. In this study, we synthesize PMPC-lipids with polymerization degrees of 10 (MPC10-lipid), 20 (MPC20-lipid), 50 (MPC50-lipid), and 100 (MPC100-lipid), and coated liposomes with 1, 5, or 10 mol% PMPC-lipids (PMPC-liposomes). Non-modified and PEGylated liposomes are used as controls. We investigate the liposome size, surface charge, polydispersity index, and adsorption of plasma proteins to the liposomes post incubation in human plasma containing N,N,N ',N '-ethylenediamine tetraacetic acid (EDTA) or lepirudin by some methods such as sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), western blotting, and automated capillary western blot, with emphasis on the binding of complement protein C3. It is shown that the coating of liposome PMPC-lipids can suppress protein adsorption more effectively with an increase in the molecular weight and molar ratio (1-10 mol%). Apolipoprotein A-I is detected on PMPC-liposomes with a higher molecular weight and higher molar ratio of PMPC-lipids, whereas alpha(2)-macroglobulin is detected on non-modified, PEGylated, and PMPC-liposomes with a shorter polymer chain. In addition, a correlation is shown among the PMPC molecular weight, molar ratio, and C3 binding. The MPC10-lipid cannot inhibit C3 binding efficiently, whereas surface modifications with 10 mol% MPC20-lipid and 5 mol% and 10 mol% MPC50-lipid suppress both total protein and C3 binding. Hence, liposome modification with PMPC-lipids can be a possible strategy for avoiding complement activation.
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| 4. |
- Adler, Anna, et al.
(författare)
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Regulation of the innate immune system by fragmented heparin-conjugated lipids on lipid bilayered membranes in vitro
- 2023
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry. - 2050-750X .- 2050-7518. ; 11:46, s. 11121-11134
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Tidskriftsartikel (refereegranskat)abstract
- Surface modification with heparin is a powerful biomaterial coating strategy that protects against innate immunity activation since heparin is a part of the proteoglycan heparan sulfate on cell surfaces in the body. We studied the heparinization of cellular and material surfaces via lipid conjugation to a heparin-binding peptide. In the present study, we synthesized fragmented heparin (fHep)-conjugated phospholipids and studied their regulation of the innate immune system on a lipid bilayered surface using liposomes. Liposomes have versatile applications, such as drug-delivery systems, due to their ability to carry a wide range of molecules. Owing to their morphological similarity to cell membranes, they can also be used to mimic a simple cell-membrane to study protein–lipid interactions. We investigated the interaction of complement-regulators, factor H and C4b-binding protein (C4BP), as well as the coagulation inhibitor antithrombin (AT), with fHep-lipids on the liposomal surface. Herein, we studied the ability of fHep-lipids to recruit factor H, C4BP, and AT using a quartz crystal microbalance with dissipation monitoring. With dynamic light scattering, we demonstrated that liposomes could be modified with fHep-lipids and were stable up to 60 days at 4 °C. Using a capillary western blot-based method (Wes), we showed that fHep-liposomes could recruit factor H in a model system using purified proteins and assist in the degradation of the active complement protein C3b to iC3b. Furthermore, we found that fHep-liposomes could recruit factor H and AT from human plasma. Therefore, the use of fHep-lipids could be a potential coating for liposomes and cell surfaces to regulate the immune system on the lipid surface.
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| 5. |
- Adler, Anna, et al.
(författare)
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Regulation of the innate immune system by fragmented heparin-conjugated lipids on lipid bilayered membranes in vitro
- 2023
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry. - 2050-750X .- 2050-7518. ; 11:46, s. 11121-11134
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Tidskriftsartikel (refereegranskat)abstract
- Surface modification with heparin is a powerful biomaterial coating strategy that protects against innate immunity activation since heparin is a part of the proteoglycan heparan sulfate on cell surfaces in the body. We studied the heparinization of cellular and material surfaces via lipid conjugation to a heparin-binding peptide. In the present study, we synthesized fragmented heparin (fHep)-conjugated phospholipids and studied their regulation of the innate immune system on a lipid bilayered surface using liposomes. Liposomes have versatile applications, such as drug-delivery systems, due to their ability to carry a wide range of molecules. Owing to their morphological similarity to cell membranes, they can also be used to mimic a simple cell-membrane to study protein-lipid interactions. We investigated the interaction of complement-regulators, factor H and C4b-binding protein (C4BP), as well as the coagulation inhibitor antithrombin (AT), with fHep-lipids on the liposomal surface. Herein, we studied the ability of fHep-lipids to recruit factor H, C4BP, and AT using a quartz crystal microbalance with dissipation monitoring. With dynamic light scattering, we demonstrated that liposomes could be modified with fHep-lipids and were stable up to 60 days at 4 degree celsius. Using a capillary western blot-based method (Wes), we showed that fHep-liposomes could recruit factor H in a model system using purified proteins and assist in the degradation of the active complement protein C3b to iC3b. Furthermore, we found that fHep-liposomes could recruit factor H and AT from human plasma. Therefore, the use of fHep-lipids could be a potential coating for liposomes and cell surfaces to regulate the immune system on the lipid surface.
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| 6. |
- Arza, Carlos R., et al.
(författare)
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Biocompatible non-leachable antimicrobial polymers with a nonionic hyperbranched backbone and phenolic terminal units
- 2022
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Ingår i: Journal of Materials Chemistry B. - : Royal Society of Chemistry (RSC). - 2050-750X .- 2050-7518. ; 10:39, s. 8064-8074
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Tidskriftsartikel (refereegranskat)abstract
- This work aimed to develop biocompatible non-leachable antimicrobial polymers without ionic structures. A series of nonionic hyperbranched polymers (HBPs) with an isatin-based backbone and phenolic terminal units were synthesized and characterized. The molecular structures and thermal properties of the obtained HBPs were characterized by SEC, NMR, FTIR, TGA and DSC analyses. Disk diffusion assay revealed significant antibacterial activity of the obtained phenolic HBPs against nine different pathogenic bacteria. The presence of a methoxy or long alkyl group close to the phenolic unit enhanced the antibacterial effect against certain Gram positive and negative bacteria. The obtained nonionic HBPs were blended in polyester poly(hexamethylene terephthalate) films, which showed no noticeable leakage after being immersed in water for 5 days. Finally, these HBPs showed no cytotoxicity effect to MG-63 osteoblast-like human cells according to MTT analysis, and negligible hemolytic effect.
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| 7. |
- Azahar Ali, Md., et al.
(författare)
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A biofunctionalized quantum dot-nickel oxide nanorod based smart platform for lipid detection
- 2016
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Ingår i: Journal of materials chemistry. B. - : ROYAL SOC CHEMISTRY. - 2050-750X .- 2050-7518. ; 4:15, s. 2706-2714
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Tidskriftsartikel (refereegranskat)abstract
- A reagent-free, low-cost and sensitive immunosensor has been fabricated using anti-apolipoprotein B (AAB) conjugated L-cysteine in situ capped cadmium sulfide quantum dots (CysCdS QDs) bound to nickel oxide nanorods (nNiO) for detection of low density lipoprotein (LDL) molecules in human serum samples. The structural and morphological properties of AAB conjugated CysCdS QDs and nNiO have been investigated using electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and UV-visible techniques. In this immunosensor, the synthesized NiO nanorods act as mediators that allow the direct electron transfer due to their channeling effect resulting in a mediator-free biosensor. This mediator-free CysCdS-NiO based immunosensor shows improved characteristics such as a good sensitivity of 32.08 mu A (mg dl(-1))(-1) cm(-2) compared to that based on nNiO (1.42 mA (mg dl(-1))(-1) cm(-2)) alone for detection of lipid (LDL) molecules over a wide concentration range, 5-120 mg dl(-1) (0.015-0.36 mu M). The kinetic analysis yields an association constant (K-a) of 3.24 kM(-1) s(-1), indicating that the antibody conjugated CysCdS-NiO platform has a strong affinity towards lipid molecules. The excellent electron transport properties of the CysCdS-NiO nanocomposite in this immunosensor reveal that it provides an efficient platform for routine quantification of LDL molecules in real samples.
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| 8. |
- Bai, Xuan, et al.
(författare)
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Sequential macrophage transition facilitates endogenous bone regeneration induced by Zn-doped porous microcrystalline bioactive glass
- 2021
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry. - 2050-750X .- 2050-7518. ; 9:12, s. 2885-2898
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages play an important role in the immune microenvironment during bone healing, and sequential macrophage phenotypic transition could achieve superior osteogenic outcomes. Microcrystalline bioactive glasses (MCBGs) with osteoimmunomodulatory effects show potential in bone tissue regeneration. Zinc (Zn) has been approved to coordinate innate and adaptive immunity. Therefore, in this study, different amounts of ZnO were incorporated into microcrystalline bioactive glass to improve its immunomodulatory ability. The effect of Zn-MCBG ionic extracts on macrophage transition was studied, and the 5Zn-MCBG extracts could orchestrate sequential M1-to-M2 macrophage transition and promote the expression of proinflammatory and anti-inflammatory genes and cytokine expression to induce human bone marrow stromal cells (hBMSCs) osteogenic differentiation in vitro. Macroporous Zn-MCBG scaffolds containing mesopores were fabricated and showed good cell adhesion and feasible apatite formation when immersed in SBF in vitro. Furthermore, a rat calvarial defect model was used to confirm that the Zn-MCBG scaffold could modulate macrophage phenotypic transition and create a desirable osteogenic microenvironment to promote osteogenesis in vivo.
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| 9. |
- Barman, Snigdha Roy, et al.
(författare)
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Dendrimer as a multifunctional capping agent for metal nanoparticles for use in bioimaging, drug delivery and sensor applications
- 2018
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Ingår i: Journal of materials chemistry. B. - : ROYAL SOC CHEMISTRY. - 2050-750X .- 2050-7518. ; 6:16, s. 2368-2384
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Forskningsöversikt (refereegranskat)abstract
- Advances in nanoparticle research, particularly in the domain of surface-engineered, function-oriented nanoparticles, have had a profound effect in many areas of scientific research and aided in bringing unprecedented developments forward, particularly in the biomedical field. Surface modifiers/capping agents have a direct bearing on the major properties of metal nanoparticles (MNPs), ranging from their physico-chemical properties to their stability and functional applications. Among the different classes of capping agents, dendrimers have gained traction as effective multifunctional capping agents for MNPs due to their unique structural qualities, dendritic effect and polydentate nature. Dendrimer-coated metal nanoparticles (DC-MNPs) are typically produced by both (i) a one-pot strategy, where metal ions are reduced in the presence of dendrimer molecules and (ii) a multi-pot strategy, where a sequence of reactions involving the reduction of metal ions, activation, conjugation and purification steps are involved. These DC-MNPs have shown remarkable ability to stabilize MNPs by means of electrostatic interactions, coordination chemistry or covalent attachment, due to them entailing a large number of sites at which further molecular moieties can be conjugated. This review article is an attempt to consolidate the on-going work, particularly over the last five years, in the field of the synthesis of dendrimer-coated MNPs and their potential applications in bioimaging, drug delivery and biochemical sensors.
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| 10. |
- Baumgartner, Johanna, et al.
(författare)
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Switchable presentation of cytokines on electroactive polypyrrole surfaces for hematopoietic stem and progenitor cells
- 2018
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Ingår i: Journal of Materials Chemistry B. - Cambridge : Royal Society of Chemistry. - 2050-750X .- 2050-7518. ; 6:28, s. 4665-4675
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cells are used in transplantations for patients with hematologic malignancies. Scarce sources require efficient strategies of expansion, including polymeric biomaterials mimicking architectures of bone marrow tissue. Tissue microenvironment and mode of cytokine presentation strongly influence cell fate. Although several cytokines with different functions as soluble or membrane-bound mediators have already been identified, their precise roles have not yet been clarified. A need exists for in vitro systems that mimic the in vivo situation to enable such studies. One way is to establish surfaces mimicking physiological presentation using protein-immobilization onto polymer films. However these films merely provide a static presentation of the immobilized proteins. It would be advantageous to also dynamically change protein presentation and functionality to better reflect the in vivo conditions. The electroactive polymer polypyrrole shows excellent biocompatibility and electrochemically alters its surface properties, becoming an interesting choice for such setups. Here, we present an in vitro system for switchable presentation of membrane-bound cytokines. We use interleukin IL-3, known to affect hematopoiesis, and show that when immobilized on polypyrrole films, IL-3 is bioavailable for the bone marrow-derived FDC-P1 progenitor cell line. Moreover, IL-3 presentation can be successfully altered by changing the redox state of the film, in turn influencing FDC-P1 cell viability. This novel in vitro system provides a valuable tool for stimuli-responsive switchable protein presentation allowing the dissection of relevant mediators in stem and progenitor cell behavior.
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