A targeting multiple-stimuli responsive POSS-based smart nanomaterial for enhanced chemo-photothermal synergistic therapy

The combination of chemotherapy and photothermal therapy has garnered significant attention in the field of multimodal cancer therapy. However, achieving precise and controllable delivery of therapeutic agents remains a challenge. In this study, we designed a biocompatible smart nanomaterial (PSD-FA) for efficient loading of doxorubicin (DOX) through dynamic chemical bonding, with the aim of achieving responsive behavior to both the tumor microenvironment (TME) and external laser irradiation. The incorporation of PEG into the nanoplatform enhanced hydrophilicity of PSD-FA NPs. Folic acid (FA) served as a targeting ligand to guide the nanoparticles tumor sites. On one hand, SQ-N acted as an effective photothermal agent that efficiently converted light energy into heat energy upon stimulation by exogenous near-infrared light. This localized increase in temperature at the tumor site facilitated targeted killing of tumor cells. On the other hand, after photothermal therapy-induced tumor ablation, DOX was released in response to redox stimuli due to significantly higher concentrations of glutathione (GSH), an antioxidant presents in TME. This allowed deep penetration into the tumor tissue, expanding the attack area and inhibiting nucleic acid synthesis in tumor cells, ultimately leading to cell death. Both in vitro and in vivo experiments demonstrated excellent anticancer efficacy of PSD-FA NPs. Overall, this intelligent nanomaterial successfully achieved targeted drug delivery with redox-responsive release capabilities while synergistically combining chemo-photothermal therapies, thus exhibiting great potential for clinical applications.