One-pot synthesized nano-heterostructure with dual-modal catalytic ROS generation ability for high-metastatic orthotopic osteosarcoma therapy

Abstract

Reactive oxygen species (ROS) played an essential role in regulating various physiological functions in living organisms and treatment of malignant disease. Herein, a new type of PEGylated carbon nitride nanosheet@copper-doped polyaniline (CNNS@CuPANI) with nano-heterostructure and dual-modal catalytic ROS generation performance was synthesized. Formation of the nano-heterostructure promoted separation of photo-induced electron-hole pairs, and doping of Cu2+ further increased electron-transfer rate greatly. Besides, antenna effect of the CuPANI endowed the heterostructure with near-infrared light utilization ability, finally inducing concurrences of oxygen-independent type I and oxygen-dependent type II photodynamic therapy simultaneously. Interestingly, unleashing of doped Cu2+ ions responded to reductive glutathione in tumor microenvironment further triggered a Fenton-like reaction, and such PEGylated CNNS@CuPANI with remarkable ROS generation ability was therefore employed for high-metastatic orthotopic osteosarcoma therapy. Cell proteomics analysis illustrated that cell survival and adhesion were considerably altered by the massively-generated ROS, which also affected efficiencies of conspicuous orthotopic tumor therapy and pulmonary metastasis resistance in vivo. To summarize, our newly-proposed PEGylated CNNS@CuPANI achieved desirable effects on killing orthotopic osteosarcoma and preventing metastasis, providing a new therapeutic strategy for malignant tumor treatment.