Journal article

Generalizable Strategy for Engineering Protein Particles with pH-Triggered Disassembly and Recoverable Protein Functionality

Tomoya Suma, Jiwei Cui, Markus Muellner, Yi Ju, Junling Guo, Ming Hu, Frank Caruso

ACS MACRO LETTERS | AMER CHEMICAL SOC | Published : 2015

Abstract

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 eviden..

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Grants

Awarded by Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology


Awarded by Australian Research Council (ARC)


Funding Acknowledgements

This research was conducted and funded by the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology (project number CE140100036). This work was also supported by the Australian Research Council (ARC) under the Australian Laureate Fellowship (F.C., FL120100030) and Super Science Fellowship (F.C., FS110200025) schemes. M.M. is grateful to The University of Melbourne for a McKenzie Fellowship.