A Facile Strategy for PEGylated Nanoprodrug of Bortezomib with Improved Stability, Enhanced Biocompatibility, pH‐Controlled Disassembly, and Release

The therapeutic efficacy of bortezomib (BTZ) is often limited due to low solubility, poor stability in vivo and nonspecific toxicity. Herein, a kind of catechol-functionalized polyethylene glycol (mPEG-CA) is first synthesized and then mPEG-CA is readily used to conjugate with BTZ by the formation of dynamic boronate bonds to obtain PEGlyated BTZ prodrug (mPEG-CA-BTZ) with the ability of pH-controlled disassembly and drug release. The structure and morphology, physicochemical characteristics, drug loading, and release as well as in vitro cytotoxicity of mPEG-CA-BTZ nanoparticles are investigated in detail. The results demonstrated that mPEG-CA-BTZ can not only self-assemble into nanostructures with uniform size and stable dispersion in physiological pH condition (pH 7.4) but also respond to the tumor acid microenvironment and achieve pH-controlled BTZ release by acid-triggered cleavage of boronate bonds, decomposition of mPEG-CA-BTZ and thus disassembly of mPEG-CA-BTZ nanoparticles. mPEG-CA-BTZ nanoparticles are expected to have great potential as a promising nanoplatform for pharmaceutical formulations of BTZ to increase therapeutic efficacy and decrease side effects of BTZ. Considering the easily available and biocompatible excipients and simple preparation process, the strategy designed herein provides a facile and promising approach to synergistically integrate the function of PEGylation and pH-sensitiveness into boronic acid-containing small molecule pharmaceutical agents.