Molecular design of a high-performance polymeric carrier for delivery of a variety of boronic acid-containing drugs

Abstract

Because of their many useful and unique properties, boronic acids are well suited for biomedical applications such as antitumor chemotherapy and boron neutron capture therapy (BNCT). Bortezomib, a boronic acid derivative, has drawn a lot of attention as a potent proteasome inhibitor. Nevertheless, because of rapid excretion and off-target effects, the clinical translation of boronic acid-containing drugs is limited. To this end, we employed a polymeric carrier to stably encapsulate boronic acid-containing drugs and achieve superior pharmacokinetics with an on-target drug release capability. Accordingly, to construct a supramolecular polymeric nanoparticle, we took advantage of the facile, stable, and pH-sensitive conjugation between boronic acids and diethanolamine-installed polymeric carriers. We demonstrated the feasibility of our molecular design by generating and applying bortezomib-loaded nanoparticles to a subcutaneous tumor-bearing mouse model. Stable encapsulation and pH-sensitive release of bortezomib facilitated antitumor efficacy and alleviated hepatotoxicity. We also verified the versatility of our approach through biological evaluations of the nanoparticles encapsulating benzo(b)thiophene-2-boronic acid, phenylboronic acid, and p-phenylene-diboronic acid.