Endogenous stimuli-sensitive multistage polymeric micelleplex anticancer drug delivery system for efficient tumor penetration and cellular internalization

Advanced Healthcare Materials
Junjie LiZhishen Ge

Abstract

To efficiently deliver anticancer drugs to the entire tumor tissue and cancer cells, an endogenous stimuli-sensitive multistage polymeric micelleplex drug delivery system is developed via electrostatic complexation between poly(ethylene glycol)-block-poly[(N'-dimethylmaleoyl-2-aminoethyl)aspartamide]-block-poly(ε-caprolactone) (PEG-b-PAsp(EDA-DM)-b-PCL) triblock copolymer micelles and cisplatin prodrug (Pt(IV))-conjugated cationic poly(amidoamine) dendrimers (PAMAM-Pt(IV)). The micelleplexes maintain structural stability at pH 7.4 ensuring long blood circulation and high tumor accumulation level, while they exhibit triggered release of secondary PAMAM-Pt(IV) dendrimer nanocarriers at tumoral acidity (≈pH 6.8) due to acid-labile charge-reversal properties of PAsp(EDA-DM) component under mildly acidic condition. The released PAMAM delivery nanocarriers with small size and slightly positive charges exhibit significantly deep tumor tissue penetration and efficient cellular internalization, followed by release of active cisplatin anticancer drug in intracellular reducing medium. In vivo investigation reveals that the Pt(IV)-loading micelleplexes significantly suppress tumor growth via intravenous injection due to synergistic effect ...Continue Reading

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Apr 21, 2016·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Qinqin Cheng, Yangzhong Liu
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Dec 29, 2020·Journal of the American Chemical Society·Junjie Li, Kazunori Kataoka

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