Foe to Friend: Supramolecular Nanomedicines Consisting of Natural Polyphenols and Bortezomib

Bortezomib (BTZ) is a first-in-class boronate proteasome inhibitor used for cancer therapy, but its therapeutic efficacy is usually inhibited by dietary polyphenols due to boronate-catechol complexation. Benefiting from such dynamic covalent chemistry, herein we describe a novel class of supramolecular nanomedicines by rationally converting natural polyphenols from foe to friend through polyphenol-mediated BTZ assembly strategy. The simple conjugation of BTZ to catechol-containing natural polyphenols via boronate ester bond allows the facile formation of dynamic drug amphiphiles, with pH-dependent assembly/disassembly behaviors under different physiological conditions. Ferric ion was also incorporated into the supramolecular system via metal-phenolic coordination interaction to both introduce bioimaging function and facilitate stability of the supramolecular nanomedicines. Our investigation revealed that the supramolecular nanomedicine consisting of natural polyphenol, BTZ and ferric ion dramatically indu...