Redox-Responsive Polymeric Nanocomplex for Delivery of Cytotoxic Protein and Chemotherapeutics

ACS Applied Materials & Interfaces
Wei Qi LimYanli Zhao

Abstract

Responsive delivery of anticancer proteins into cells is an emerging field in biological therapeutics. Currently, the delivery of proteins is highly compromised by multiple successive physiological barriers that reduce the therapeutic efficacy. Hence, there is a need to design a robust and sustainable nanocarrier to provide suitable protection of proteins and overcome the physiological barriers for better cellular accumulation. In this work, polyethylenimine (PEI) cross-linked by oxaliplatin(IV) prodrug (oxliPt(IV)) was used to fabricate a redox-responsive nanocomplex (PEI-oxliPt(IV)@RNBC/GOD) for the delivery of a reactive oxygen species-cleavable, reversibly caged RNase A protein (i.e., RNase A nitrophenylboronic conjugate, RNBC) and glucose oxidase (GOD) in order to realize efficient cancer treatment. The generation of hydrogen peroxide by GOD can uncage and restore the enzymatic activity of RNBC. On account of the responsiveness of the nanocomplex to highly reducing cellular environment, it would dissociate and release the protein and active oxaliplatin drug, causing cell death by both catalyzing RNA degradation and inhibiting DNA synthesis. As assessed by the RNA degradation assay, the activity of the encapsulated RNBC was...Continue Reading

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Citations

Oct 29, 2020·Chemical Society Reviews·Jiajie ChenJianlin Shi
Dec 6, 2020·Nature Reviews. Drug Discovery·Michael J MitchellRobert Langer
Apr 27, 2021·ACS Nano·Qiuhong ZhangYanli Zhao
Aug 20, 2020·ACS Applied Materials & Interfaces·Gong ChengSi-Yang Zheng
Dec 3, 2021·Biomacromolecules·Justin M Horn, Allie C Obermeyer

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