Hyaluronic acid coated mesoporous carbon-copper peroxide for H2O2 self-supplying and near-infrared responsive multi-mode breast cancer oncotherapy

It is challenging to develop the synergistic intelligent therapeutic nanoplatform to cure cancer. In the present study, a novel nanotherapeutic platform was constructed for H2O2 self-supplying and multimodal breast cancer therapy. In which, copper peroxide nanoparticles (CP NPs) were adsorbed on the surface of mesoporous carbon nanospheres (MCN) through electrostatic attraction, followed by loading doxorubicin (DOX) into the nanocomposite (MCN-CP) and coating hyaluronic acid (HA) on the surface, the DOX/MCN-CP-HA nanoplatform was obtained. In the system, the MCN not only possessed a high DOX loading capacity, but produced excellent photothermal therapy (PTT) effect. Importantly, the ultra-small CP NPs as the Fenton agent not only could selectively self-supplying H2O2 in acidic condition, but simultaneously release Cu2+ to catalyze the production of ·OH in the presence of H2O2. Meantime, the resulting Cu2+ possessed GSH-elimination property, which afforded enhanced chemodynamic therapy (CDT). Furthermore, the outer layer HA targeted to CD44 and achieved breast cancer cell targeting. The elevated temperature from PTT and acidic tumor microenvironment accelerated the release of DOX, which enabled DOX/MCN-CP-HA as an intelligent CDT-PTT-chemotherapy synergistic nanoplatform. In vitro and in vivo pharmacodynamic evaluations confirmed the potential of the nanoplatform for CDT-PTT-chemotherapy synergistic oncotherapy of breast cancer.