Biodegradable copper-doped hollow mesoporous polydopamine nanoparticles for chemo/photothermal/chemodynamic synergistic therapy

Combination therapy has aroused widespread attention in overcoming the disadvantages of single therapies and improving treatment efficacy. Polydopamine (PDA), as a biodegradable organic photothermal material, has great potential for photothermal therapy (PTT) based combination therapy. In this work, a Cu2+-doped hollow mesoporous polydopamine (CHMP) was innovatively prepared for the first time with pH/H2O2/GSH/NIR light responsiveness for chemotherapy/PTT/chemodynamic therapy (CDT) combination therapy. By virtue of the incorporation of Cu2+, the degradability, GSH consumption ability and photothermal performance of hollow mesoporous polydopamine were significantly improved, endowing the CHMP with the ability to undergo Fenton-like reactions. Meanwhile, doxorubicin (DOX) was used as the model chemotherapeutic agent to be loaded into CHMP and grafted with PEG on the surface to construct a DOX/CHMPP nanoplatform. The photothermal conversion efficiency of CHMPP reached 40.64%, which could not only facilitate the thermal motion of drug molecules, enhance tumor cells uptake to drugs, but also promote the production of •OH. We evaluated the degradation behaviors of CHMPP and elucidated the feasible degradation process. Moreover, the cellular tests exhibited that DOX/CHMPP had remarkable synergistic therapeutic effects in tumor treatment involving chemo/PTT/CDT with a lower IC50 of 0.73 μg/mL than that of DOX/CHMPP without NIR light irradiation (7.67 μg/mL). The in vivo anti-tumor effect suggested that the nanoplatform could accumulate in tumor sites to exert the ability of thermal imaging and have significantly synergistic therapeutic effect. Therefore, CHMPP could be used as a promising nanoplatform for PTT based combination therapy.