期刊
ACS MACRO LETTERS
卷 4, 期 2, 页码 160-164出版社
AMER CHEMICAL SOC
DOI: 10.1021/mz5007443
关键词
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资金
- Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology [CE140100036]
- Australian Research Council (ARC) [FL120100030, FS110200025]
- University of Melbourne
Protein particles are promising candidates for therapeutic delivery. In this study, we report a generalizable strategy to assemble a series of proteins into pH-cleavable protein particles that recover protein functionality after disassembly. Our strategy uses an acid-labile reversible cross-linker based on maleic anhydride chemistry, which allows the cross-linking of proteins and releases unmodified proteins upon cleavage, causing minimal loss of protein functionality. The protein particles can be rapidly disassembled at a mildly acidic pH (<6.5) and inside cells with negligible cytotoxicity. Furthermore, cleavage of the cross-linker led to above 97% recovery of enzymatic activity, as evidenced by using glucose oxidase. This facile and robust strategy to engineer pH-cleavable protein particles may provide a new platform for therapeutic protein delivery as well as for small molecule drug and nucleic acid delivery.
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