Photothermal and pH-stimuli-responsive mesoporous silica nanoparticles drug delivery system for targeting the tumor cells.

To improve the precision of cancer therapy, multi-stimuli responsiveness and targeted, controllable drug release are essential components. In this study, we designed an intelligent drug delivery system that integrates chemotherapy and photothermal therapy with pH- and photothermal-sensitive controlled drug release capabilities. This system encapsulates CuS nanoparticles and a model drug Metformin (Met) within Mesoporous Silica Nanoparticles (MSN), which are subsequently coated with a thin layer of Polydopamine (PDA) to enhance multiple photothermal conversion functions. Met, widely recognized for its role in treating type 2 diabetes, has been shown to possess anti-tumor properties. Consequently, it was chosen as the model drug encapsulated within the mesoporous silica nanoparticles. Our investigation about the drug release behavior demonstrated that the PDA coating on MSN not only mitigates the initial burst release of metformin but also facilitates sustained, pH- and thermally-responsive release at pH 6.5, achieving a cumulative release of 67.1% by the tenth day. Furthermore, the PDA modification significantly improves the photothermal conversion performance and stability of CuS@MSN. The photothermal conversion efficiency (PCE) of CuS@MSN and CuS@MSN@PDA (CMP) were measured at 42.7% and 59.9%, respectively. Additionally, on the 28th day post-tumor resection, the met@CMP group exhibited an 80% lower tumor recurrence rate compared to the met group alone. This research highlights the substantial potential of intelligent CMP nanoparticles for multi-stimuli responsive, precise chemo-photothermal synergistic therapy in cancer treatment.