Liu, Shaoqiong Ono, Robert J. Yang, Chuan Gao, Shujun Ming Tan, Jordan Yong Hedrick, James L. Yang, Yi Yan Dual pH-Responsive Shell-Cleavable Polycarbonate Micellar Nanoparticles for in Vivo Anticancer Drug Delivery 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 <sup>1</sup>H 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-cleavable nanoparticles are a potentially promising carrier for BTZ delivery. pH-responsive diblock copolymers;Dual pH-Responsive Shell-Cleavable Polycarbonate Micellar Nanoparticles;pH-responsive boronate ester bond;1 H NMR;drug loading capacity;micelle;BTZ;breast cancer cells;Vivo Anticancer Drug Delivery;phenylboronic acid group;breast cancer BT -474 xenograft mouse model;acidic tumor tissues;pH-responsive shell-cleavable nanoparticles;micellar nanoparticles;acid-labile acetal bond 2018-05-14
    https://acs.figshare.com/articles/journal_contribution/Dual_pH-Responsive_Shell-Cleavable_Polycarbonate_Micellar_Nanoparticles_for_in_Vivo_Anticancer_Drug_Delivery/6387377
10.1021/acsami.8b01954.s001