Photonic hyperthermal and sonodynamic nanotherapy targeting oral squamous cell carcinoma

Abstract

Nanomedicine that enables multiple synergetic treatments provides effective non-invasive treatment modalities for cancer therapy. Yet treatments for oral squamous cell carcinoma (OSCC) are rarely reported. Here, we designed OSCC-targeting multi-functional nanomedicines to overcome the therapeutic obstacles during OSCC treatments, including ineffective chemotherapy, and the traumatic surgery and radiotherapy. The urokinase plasminogen activator receptor (uPAR)-targeting ligand AE105 decorated dendritic mesoporous silica nanoparticles (DMSN) encapsulating photonic active ultrasmall Cu_2−xS NPs and sonosensitizer Rose Bengal (RB) have been rationally designed and constructed (designated as Cu_2−xS-RB@DMSN-AE105, abbreviated as CRDA). These CRDAs initially target the uPAR, which is overexpressed in the OSCC cell membrane, to increase the localized accumulation of CRDAs at tumor sites. Under the irradiation of both near-infrared laser and ultrasound, the in situ photonic-hyperthermal and sonodynamic effects are respectively enabled to induce the cell death of OSCC. Upon both in vitro/in vivo challenges, tumor cells/xenografts have been efficiently eradicated, achieving the targeting and synergetic treatment modality against the OSCC with satisfactory biocompatibility.