Multifunctional chemoreactive nanosonosensitizers exert antitumoral, antibacterial and wound healing effects on malignant peripheral nerve sheath tumors

Abstract

Currently, surgery is the only available and effective clinical strategy for treating malignant peripheral nerve sheath tumors. However, even with complete surgical resection, poor physical health or cachexia can cause wound delay or infection. To solve this critical issue, DSF-CuO2@DMSN nanoparticles were rationally designed. These nanoparticles have been engineered to exert high performance and synergistic sonodynamic/chemodynamic/chemotherapeutic tumor treatment under the stimulation of ultrasound by producing reactive oxygen species and dithiocarbamate − copper complexes in situ in response to the tumor-specific acidic and hypoxic microenvironment. When mixed with thermosensitive hydrogels, the therapeutic effects of nanosonosensitizers can be precisely limited to the working areas. Significant inhibition of proliferation, increases in apoptosis and death in tumor cells and xenograft all demonstrated the antitumoral capability of DSF-CuO2@DMSN under ultrasound stimulation. The upregulated expression of caspase-3 related proteins and the results of RNA sequencing indicated the induction of cell apoptosis, autophagy, or cell death after treatment. Moreover, DSF-CuO2@DMSN induced strong antibacterial effects and wound healing abilities under the activation of ultrasound, with quick wound closure and the absence of bacterial infection in in vitro and in vivo experiments. Altogether, the multifunctional DSF-CuO2@DMSN nanoagents can provide a distinct postoperative therapeutic strategy for both tumor inhibition and wound recovery.