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In Situ Forming Hydrogels via Catalyst-Free and Bioorthogonal “Tetrazole–Alkene” Photo-Click Chemistry
来源:邓超教授个人网站 发布日期:2014-07-24
作者:Y.P. Fan, C. Deng*, R. Cheng, F.H. Meng, and Z.Y. Zhong*
关键字:hydrogel, click chemistry, in situ forming, protein release
论文来源:期刊
具体来源:Biomacromolecules
发表时间:2013年
In situ forming hydrogels were developed from 4-arm poly(ethylene glycol)?methacrylate (PEG-4-MA) and ?tetrazole (PEG-4-Tet) derivatives through catalyst-free and bioorthogonal “tetrazole?alkene” photo-click chemistry. PEG-4-MA and PEG-4-Tet (Mn = 10 kg/mol) were soluble at 37 °C in phosphate buffer (PB, pH 7.4, 10 mM) at total polymer concentrations ranging from 20 to 60 wt % but formed fluorescent hydrogels upon 365 nm UV irradiation at an intensity of 20.6, 30.7, or 60 mW/cm2. The gelation times ranged from ca. 50 s to 5 min, and storage moduli varied from 0.65 to 25.2 kPa depending on polymer concentrations and degrees of Tet substitution in PEG-4-Tet conjugates. The cell experiments via an indirect contact assay demonstrated that these “tetrazole?alkene” photo-click PEG hydrogels were noncytotoxic. The high specificity of photo-click reaction renders thus
obtained PEG hydrogels particularly interesting for controlled protein release. Notably, in vitro release studies showed that cytochrome c (CC), γ-globulins (Ig), and recombinant human interleukin-2 (rhIL-2) all were released from PEG hydrogels in a
sustained and quantitative manner over a period of 14?20 days. Importantly, released CC and rhIL-2 exhibited comparable biological activities to native CC and rhIL-2, respectively. These results confirm that “tetrazole?alkene” photo-click reaction is
highly compatible with these loaded proteins. This photo-controlled, specific, efficient, and catalyst-free click chemistry provides a new and versatile strategy to in situ forming hydrogels that hold tremendous potentials for protein delivery and tissue
engineering.
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