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

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.