Targeted embolization and chemotherapy for solid tumors by microenvironment-responsive poly(amino acid)s

Abstract

Transcatheter arterial embolization (TAE) has been used to treat advanced and unresectable tumors, whose treatment is complex and may involve other risks. Here, inspired by the acid and reductive microenvironment of the solid tumors, a new approach for noninvasive and targeted intravenous embolization and chemotherapy is developed. The method was based on a series of acid microenvironment-responsive polypeptides poly[(L-Glutamic acid -ran-L-Tyrosine) -b-L-Threonine-b-L-Cysteines]s, PGTTCs.) to construct the reduction-responsive chemoembolic agent by grafting modified paclitaxel (HS-PTX) to sulfhydryl side groups on PGTTCs for noncatheter targeted-embolization, which effectively improved the solubility of paclitaxel. HS-PTX could release in the presence of glutathione (GSH) due to disulfide bond disruption in vitro, and the results of tumor-bearing mice experiments showed that these polypeptides could effectively target to the tumor, embolize the tumor supply vessels rapidly and release paclitaxel in tumor sites. By comparing the therapeutic effect of embolization therapy only with that of embolization combined with chemotherapy, the chemoembolization agent showed excellent effect of embolization chemotherapy in subcutaneous tumor models, and cured tumor in mice within 20 days. Therefore, this polypeptide is expected to be a favorable candidate for effective catheterless inteavenous embolization combined with chemotherapy.