Tumor-targeting multi-shelled hollow nanospheres as drug loading platforms for imaging-guided combinational cancer therapy
Wentao Wang, Tao Zheng, Ming Zhang, Qicheng Zhang, Fan Wu, Yihan Liu, Lin Zhang, Jun Zhang, Mingqian Wang, Yi Sun
Abstract
In this work, we developed multi-shelled hollow nanospheres [RGD@am-ZnO@CuO@Au@DOX HNSs] as multifunctional therapeutic agents to achieve effective and targeted Zn2+/Cu2+ therapy, induced drug delivery under low pH/red-light conditions, and enhanced phototherapy under single red-light. The photothermal and photodynamic performance of am-ZnO@CuO@Au HNSs was enhanced relative to that of am-ZnO nanoparticles (NPs) or am-ZnO@CuO HNSs by utilizing the resonance energy transfer process and broad red-light absorption. The pH-sensitive am-ZnO@CuO@Au HNSs were dissolved to Zn2+/Cu2+ in the acidic endosomes/lysosomes of cancer cells, resulting in a cancer cell killing effect. The release performance of doxorubicin (DOX) from RGD@am-ZnO@CuO@Au@DOX HNSs was evaluated under low pH and red-light-irradiated conditions, and targeting of HNSs was confirmed by dual-modal imaging (magnetic resonance/fluorescence) of the tumor area. Moreover, in vivo synergistic therapy using RGD@am-ZnO@CuO@Au@DOX HNSs was further evaluated in mice bearing human pulmonary adenocarcinoma (A549) cells, achieving a remarkable synergistic antitumor effect superior to that obtained by monotherapy. This study validated that RGD@am-ZnO@CuO@Au@DOX HNSs can be a promising candidate for efficient postoperative cancer therapy.