Functionalized g-C3N4 nanosheets for potential use in magnetic resonance imaging-guided sonodynamic and nitric oxide combination therapy

Abstract

The oxygen consumption-induced hypoxia and the high concentration of glutathione in tumor microenvironment limit the treatment outcomes of sonodynamic therapy (SDT). SDT needs to be combined with other treatment modalities to achieve the desired therapeutic efficiency. In this study, an oxidized g-C3N4 (OCN) nanosheet-based theranostic nanoplatform is developed for sonodynamic and nitric oxide (NO) combination therapy of cancer. The OCN nanosheets are successively modified with amino-terminated 6-armed polyethylene glycol, chlorin e6, and Gd3+ ions, and then the as-prepared OCN-PEG-(Ce6-Gd3+) nanosheets are loaded with the NO donor N,N′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine (BNN6). Upon ultrasound (US) irradiation, the OCN-PEG-(Ce6-Gd3+)/BNN6 nanocomposite can induce the generation of reactive oxygen species (ROS) and simultaneously release NO molecules to effectively kill the cancer cells, thereby significantly suppressing the tumor growth. Moreover, a good in vivo T1-weighted magnetic resonance imaging (MRI) contrast effect is achieved after intravenous injection of OCN-PEG-(Ce6-Gd3+)/BNN6 due to remarkably enhanced contrast performance of the nanocomposite. Therefore, the OCN-PEG-(Ce6-Gd3+)/BNN6 formulation can serve as a promising theranostic agent for MRI-guided sonodynamic-NO combination therapy.