Enhanced glutamine inhibition and photothermal therapy for breast cancer using Janus mesoporous organosilica‐coated platinum nanomotors

Abstract In the treatment of breast cancer, the combination of glutamine metabolism inhibition and photothermal therapy (PTT) is gaining increasing attention. This study developed a Janus nanomotor to enhance permeability in tumor tissues for nanomedicine applications by using mesoporous organic silica (PMO) anisotropically grown on the surface of the platinum (Pt) nanoparticles (PMO@Pt). The prepared PMO@Pt had unique Janus structure with an average size of approximately 236 nm. The loading capacity of V9302 was evaluated to be 44.37% when the mass ratio of V9302 to PMO@Pt was maintained at 2.0 and in vitro release studies demonstrated that acidic environments significantly enhanced the drug release. Then this nanomotor was loaded with perfluorohexane (PFH), a phase‐change material, and the glutamine inhibitor V9302 (denoted as Janus PMO@Pt@PFH@V9302, JPV). Janus PMO@Pt@PFH (JPP) nanomotors demonstrated enhanced fluorescence intensity and distribution within 3D tumor spheroids compared to Janus PMO@Pt nanomotors, attributed to the photothermal‐induced phase change of PFH. The nanomotors exhibited high biocompatibility, with cell viability exceeding 98% at high concentrations. However, the incorporation of V9302 into the nanomotors (JPV) significantly reduced 4T1 cell viability under laser irradiation, indicating a cytotoxic effect resulting from the synergy between photothermal therapy and glutamine metabolism inhibition. In vivo, JPV nanomotors effectively inhibited tumor growth and induced apoptosis without causing significant systemic toxicity, showcasing their potential as a therapeutic agent for breast cancer. This integrated nanomotor offers a promising approach for enhanced ultrasound imaging and photothermal therapy in cancer treatment.