Benzoxaborole Ester‐Based Alternating Copolymer Nanoaggregates with Triple‐Stimuli Response

Abstract

AbstractAn innovative amphiphilic alternating copolymer with benzoxaborole ester‐linkages (P(NODGA‐alt‐PBA)) is synthesized in one step through an amination reduction reaction involving N‐octyl‐d‐glucamine and 2‐formylphenylboronic acid. Under CO2, lactic acid (LA) and H2O2 stimulations, nanoaggregates self‐assembled by P(NODGA‐alt‐PBA) can undergo cleavage via the breaking of benzoxaborole ester bonds, which is confirmed by analysis of UV–vis absorption spectra, dynamic light scattering, and transmission electron microscopy. As triggered by these stimuli, doxorubicin‐loaded nanocarriers (DOX‐PNs) are disrupted and quickly release drug, afterward only leaving some small molecular residues with low toxicity that can be absorbed and utilized by biological tissues. In vitro results indicate that P(NODGA‐alt‐PBA) is non‐toxic but DOX‐PN exhibits a markly enhanced therapeutic effect of DOX, compared to free DOX, ascribing to the tertiary amino protonated. This approach provides a promising candidate for biocompatible, biodegradable, and safe drug carriers for cancer therapy.