fosbretabulin and Nasopharyngeal-Carcinoma

In this study, we designed biodegradable polymersomes for co-delivery of an antiangiogenic drug combretastatin-A4 phosphate (CA4P) and doxorubicin (DOX) to collapse tumor neovasculature and inhibit cancer cell proliferation with the aim to achieve synergistic antitumor effects. The polymersomes co-encapsulating DOX and CA4P (Ps-DOX-CA4P) were prepared by solvent evaporation method using methoxy poly(ethylene glycol)-b-polylactide (mPEG-PLA) block copolymers as drug carriers. The resulting Ps-DOX-CA4P has vesicles shape with uniform sizes of about 50 nm and controlled co-encapsulation ratios of DOX to CA4P. More importantly, Ps-DOX-CA4P (1:10) showed strong synergistic cytotoxicity (combination index CI = 0.31) against human nasopharyngeal epidermal carcinoma (KB) cells. Furthermore, Ps-DOX-CA4P accumulated remarkably in KB tissues xenografts in nude mice. Consistent with these observations, Ps-DOX-CA4P (1:10) achieved significant antitumor potency because of fast tumor vasculature disruption and sustained tumor cells proliferation inhibition in vivo. The overall findings indicate that co-delivery of an antiangiogenic drug and a chemotherapeutic agent in polymersomes is a potentially promising strategy for cancer therapy.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Doxorubicin; Drug Carriers; Drug Combinations; Drug Compounding; Drug Synergism; Female; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Nanocapsules; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Polymers; Stilbenes; Tissue Distribution; Tumor Cells, Cultured; Xenograft Model Antitumor Assays