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Structure Activity Relationship of Heparin Mimicking Polymer p(SS-co-PEGMA): Effect of Sulfonation and Polymer Size on FGF2-Receptor Binding.

ABSTRACT: Fibroblast growth factor-2 (FGF2) is a heparin binding protein that plays a role in a range of biological functions such as wound healing and bone regeneration. Heparin, a highly sulfated glycosaminoglycan, is required for FGF2 to bind to its receptor. Therefore, polymeric mimics of heparin are widely studied for their ability to manipulate FGF2-induced biological interactions. It is known that altering the degree of sulfonated monomer incorporation and size of heparin-mimicking polymers can affect protein-receptor binding. To elucidate the relationship between degree of sulfonation and receptor binding for the heparin-mimicking polymer, poly(styrene sulfonate-co-poly(ethylene glycol) methyl ether methacrylate) (p(SS-co-PEGMA)) a library was synthesized to contain nine polymers with degrees of sulfonation ranging from 0-100%. Kinetics of the polymerization was evaluated and reactivity ratios compared to literature results. These polymers were then tested for their ability to enhance FGF2 binding with its receptor as both covalent conjugates and as excipients. In a receptor based enzyme-linked immunosorbant assay (ELISA), as well as a cell-based study, the polymer with 81% SS incorporation enhanced receptor binding compared to FGF2 alone, and to a greater extent than the other polymers. Therefore, another library of polymers was prepared maintaining the degree of sulfonation at 81% and changing the size from 41 to 390 monomer repeat units. The polymers were again tested in receptor based ELISA and cell studies, and all of the different sizes performed similarly, except for degree of polymerization 295 and 390, which had reduced response in the cellular assay. These results provide important information for the use of pSS-co-PEGMA as a potential heparin-mimicking therapeutic.

SUBMITTER: Paluck SJ

PROVIDER: S-EPMC5701782 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Structure Activity Relationship of Heparin Mimicking Polymer p(SS-<i>co</i>-PEGMA): Effect of Sulfonation and Polymer Size on FGF2-Receptor Binding.

Paluck Samantha J SJ Maynard Heather D HD

Polymer chemistry 20170705 31

Fibroblast growth factor-2 (FGF2) is a heparin binding protein that plays a role in a range of biological functions such as wound healing and bone regeneration. Heparin, a highly sulfated glycosaminoglycan, is required for FGF2 to bind to its receptor. Therefore, polymeric mimics of heparin are widely studied for their ability to manipulate FGF2-induced biological interactions. It is known that altering the degree of sulfonated monomer incorporation and size of heparin-mimicking polymers can aff ...[more]

PMID: 29181096

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Project description:Posterior capsule opacification (PCO) is a significant complication of intraocular lens (IOL) implantation in cataract surgery, in which the adhesion and proliferation of lens epithelial cells (LECs) on the implanted IOL surface play an important role. The surface modification of IOL to prevent LEC adhesion and proliferation is a practical way to reduce the incidence of PCO. In this study, a multifunctional binary copolymer of poly(ethylene glycol) methacrylate (PEGMA) and glycidyl methacrylate (GMA) was synthesized (poly(PEGMA-co-GMA), PPG) and chemically grafted onto the aminolyzed IOL surface, utilizing the coupling reaction of epoxy and amino groups. Doxorubicin (DOX) was subsequently immobilized on the surface coating via the reaction of epoxy and amino groups as well. Taking advantages of the hydrophilicity of the PEG segments in the copolymer coating and the anti-proliferative effects of the DOX, a multifunctional surface coating was easily established by the synthesized copolymer PPG. Such anti-proliferative drug immobilized hydrophilic coating modification may effectively reduce the cell adhesion and proliferation and thus it is hypothesized to have great potential in PCO inhibition. The synthesis of PPG was confirmed by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FTIR). The surface coating immobilization was demonstrated by X-ray photoelectron spectroscopy (XPS). The in vitro drug release profiles and the cell behaviors were also investigated to validate the multifunctional coating inhibition effect on cellular adhesion and antiproliferation. Finally, the in vivo ocular implantation was carried out on rabbit eyes to evaluate the effect of the coating modified IOL on the inhibition of postoperative PCO. It followed that such multifunctional coating modification can effectively inhibit the adhesion and proliferation of LECs and significantly reduce the incidence of PCO. All these results reveal that such PPG copolymer modification provides a facile yet effective way to inhibit PCO formation after IOL implantation.

Dataset Information

Structure Activity Relationship of Heparin Mimicking Polymer p(SS-co-PEGMA): Effect of Sulfonation and Polymer Size on FGF2-Receptor Binding.

Publications

Structure Activity Relationship of Heparin Mimicking Polymer p(SS-<i>co</i>-PEGMA): Effect of Sulfonation and Polymer Size on FGF2-Receptor Binding.

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