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Enzymatic Synthesis of PEG-poly(amine-co-thioether esters) as Highly Efficient pH and ROS Dual-Responsive Nanocarriers for Anticancer Drug Delivery

Abstract

Novel multifunctional drug nanocarriers have been successfully fabricated from a new type of enzymatically synthesized, biodegradable block copolymers, PEG-poly(ω-pentadecalactone-co-N-methyldiethyleneamine-co-3,3'-thiodipropionate) (PEG-PPMT), which were responsive to tumor-relevant acidic pH (5.0-6.5) and intracellular reactive oxygen species (ROS) of tumor cells. The PEG-PPMT copolymers could self-assembly to form nano-scaled particles in aqueous solutions, which are stable in the physiological solution, but swell substantially upon reducing the pH from 7.4 to 5.0 and/or in presence of ROS on account of the protonation of the tertiary amino groups and oxidation of the thioether groups, causing a hydrophobic to hydrophilic transition in the nanoparticle cores. Consistently, docetaxel (DTX)-encapsulated PEG-PPMT nanoparticles can be triggered in a synergistic manner by acidic pH and high-ROS environment in tumor cells to release the hydrophobic drug at accelerated rates for efficient tumor growth inhibition. In particular, DTX-encapsulated PEG-PPMT-11% PDL and PEG-PPMT-28% PDL nanoparticles exhibit extraordinarily enhanced potency (95% and 93% tumor-inhibiting efficiency, respectively) in inhibiting growth of ROS-rich CT-26 tumors xenografted in mice. Importantly, biosafety analyses show minimal toxicity of DTX-loaded PEG-PPMT nanoparticles toward normal organs including liver and kidney during the in vivo antitumor treatments. These results demonstrate that the PEG-PPMT nanoparticles are promising pH and ROS dual-responsive multifunctional nanocarriers for tumor site specific, controlled release of anticancer drugs to treat ROS-rich tumors.

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Publication details

The article was received on 01 Nov 2018, accepted on 04 Dec 2018 and first published on 06 Dec 2018


Article type: Paper
DOI: 10.1039/C8TB02882F
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
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    Enzymatic Synthesis of PEG-poly(amine-co-thioether esters) as Highly Efficient pH and ROS Dual-Responsive Nanocarriers for Anticancer Drug Delivery

    Y. Gong, M. Shu, J. Xie, C. Zhang, Z. Cao, Z. Jiang and J. Liu, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C8TB02882F

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