Abstract
The development of drug delivery systems with high drug-loading efficiency, kinetic stability against dilution, as well as enhanced anticancer activity is of crucial importance to the fields of self-assembly and nanomedicine. Herein, we propose a strategy where the anticancer peptide acts as water-soluble monomer to directly participate in emulsion interfacial polymerization for fabricating polypeptide nanospheres. The constructed polypeptide nanospheres hold a high drug loading efficiency of 77%, and can be stably dispersed in highly diluted aqueous solutions. The acid-labile amide linkage in polypeptide nanospheres can be hydrolyzed in tumor acidic environments, thus releasing anticancer peptides selectively. The polypeptide nanospheres achieve significantly enhanced anticancer activity against HCT116 cells in vitro and in vivo through improved mitochondrial and membrane disruption. In addition, its side effects on normal cells can be reduced significantly. It is highly anticipated that more kinds of anticancer drug candidates or anticancer drugs can be applied to fabricate polymeric nanomedicines with improved anticancer activity through this strategy.
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Acknowledgements
This work was financially supported by the Ministry of Science and Technology of China (2021YFA1501600, 2018YFA020-8900), the National Natural Science Foundation of China (21821001), and the Strategic Priority Research Program of Chinese Academy of Sciences (XDB36000000). The authors are grateful to Assoc. Prof. Yincheng Chang (Beijing University of Chemical Technology) and Dr. Bin Yuan (Renmin University of China) for their helpful discussion.
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Emulsion Interfacial Polymerization of Anticancer Peptides: Fabricating Polypeptide Nanospheres with High Drug-Loading Efficiency and Enhanced Anticancer Activity
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Yang, J., Wang, H., Yin, Z. et al. Emulsion interfacial polymerization of anticancer peptides: fabricating polypeptide nanospheres with high drug-loading efficiency and enhanced anticancer activity. Sci. China Chem. 65, 2252–2259 (2022). https://doi.org/10.1007/s11426-022-1311-3
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DOI: https://doi.org/10.1007/s11426-022-1311-3