Dual pH-Responsive Shell-Cleavable Polycarbonate Micellar Nanoparticles for in Vivo Anticancer Drug Delivery

ACS Applied Materials & Interfaces
Shaoqiong LiuYi Yan Yang

Abstract

To exploit tumor and intracellular microenvironments, pH-responsive diblock copolymers of poly(ethylene glycol) and catechol-functionalized polycarbonate with acid-labile acetal bond as the linker are synthesized to prepare micellar nanoparticles that shed the shell at acidic tumor tissues and inside cancer cells, hence accelerating drug release at the target. The pH-dependent cleavage of the shell is demonstrated at pH 5.0 and 6.5 using 1H NMR. Bortezomib (BTZ, an anticancer drug containing a phenylboronic acid group) is conjugated to the polymers through formation of pH-responsive boronate ester bond between boronic acid and catechol in the polymers. Dual pH-responsive bortezomib-polymer conjugates (BTZ-PC) self-assemble into micellar nanoparticles of small size (<110 nm) with narrow size distribution and high drug loading capacity. Acidic pH accelerates BTZ release from BTZ-PC micelles and enhances intracelluar uptake of the micelles, hence increasing in vitro cytotoxicity against human breast cancer cells. More importantly, the BTZ-PC micelles achieve a stronger antitumor effect in a human breast cancer BT-474 xenograft mouse model than free BTZ and mitigate in vivo hepatotoxicity of BTZ. These dual pH-responsive shell-clea...Continue Reading

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Citations

Nov 2, 2019·Journal of Biomaterials Science. Polymer Edition·Penghui WangBo Chi
Jan 1, 2020·Chembiochem : a European Journal of Chemical Biology·Xing Qin, Yongsheng Li
Feb 25, 2020·Drug Delivery·Chunyun WangShiyong Song
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Oct 27, 2020·Advanced Healthcare Materials·Chao WeiMeidong Lang
Feb 6, 2021·Nanomedicine·Lingyu WeiJianxun Ding
Mar 11, 2021·Biomaterials·Yuequan WangJin Sun
Jun 25, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yifan YangZhenqing Hou
Jul 3, 2021·Polymers·Teresa BasinskaStanislaw Slomkowski
Jul 2, 2021·Chemical Communications : Chem Comm·Fei LuBo Tang
Nov 30, 2021·Gels·Tisana KaewruethaiJittima Amie Luckanagul

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