Homotypic membrane-camouflaged camptothecin nanorods combining photothermal and chemotherapy for synergistic antitumor therapy.

Chemotherapy hardly achieves satisfactory therapeutic efficacy owing to the widely occurred adverse effects and drug tolerance, and the extensively investigated delivery systems suffer from complicated synthesis, low drug loading and less efficient tumor accumulation. Herein, we developed rod-shape nanocrystals to address challenges in the circulation stability, tumor targeting and therapeutic efficacy of camptothecin (CPT), a mainstay of treatments for various cancers. CPT nanorods (CNR) were coated with polydopamine (PDA) to achieve combinational chemo- and photothermal therapies (PTT) and then wrapped with cell membrane (CM) from homotypic tumor cells to obtain CNR@PDA-CM. CNR@PDA-CM retained the membrane proteins presented on 4 T1 cell surface, holding the potential to decrease phagocytic uptake and selectively accumulate in tumor cells. The integration of rod shape and CM wrapping prolongs blood circulation, and CNR@PDA-CM achieves 73-fold longer terminal half-life and nearly 5-fold higher tumor accumulation than free CPT after intravenous injection. When reaching tumor sites, PDA-mediated photothermal effect accelerates CPT release and enhances drug permeability in tumors. The combination of PTT and CPT-based chemotherapy produce robust and synergistic therapeutic outcome in metastatic breast cancer, with almost compete inhibition of tumor growth and 100 % mouse survival at the end of experiment. Thus, this study demonstrates a concise design of CNRs with high drug loading, desirable homotypic targeting, synergistic antitumor efficacy to potentially provide new insight for effective treatment of metastatic cancers.