In Situ Forming Hydrogels via Catalyst-Free and Bioorthogonal 鈥淭etrazole鈥揂lkene鈥?Photo-Click Chemistry

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• 作者：Yaping Fan ; Chao Deng ; Ru Cheng ; Fenghua Meng ; Zhiyuan Zhong
• 刊名：Biomacromolecules
• 出版年：2013
• 出版时间：August 12, 2013
• 年：2013
• 卷：14
• 期：8
• 页码：2814-2821
• 全文大小：501K
• 年卷期：v.14,no.8(August 12, 2013)
• ISSN：1526-4602

文摘

In situ forming hydrogels were developed from 4-arm poly(ethylene glycol)鈥搈ethacrylate (PEG-4-MA) and 鈭抰etrazole (PEG-4-Tet) derivatives through catalyst-free and bioorthogonal 鈥渢etrazole鈥揳lkene鈥?photo-click chemistry. PEG-4-MA and PEG-4-Tet (M_n = 10 kg/mol) were soluble at 37 掳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 鈥渢etrazole鈥揳lkene鈥?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), 纬-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鈥?0 days. Importantly, released CC and rhIL-2 exhibited comparable biological activities to native CC and rhIL-2, respectively. These results confirm that 鈥渢etrazole鈥揳lkene鈥?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.