Combination of targeted recognition and drug-triggered release multifunctional nanoplatform for fluorescence-guided synergistic photothermal/photodynamic/chemodynamic process.

Synergistic chemodynamics, photodynamic and photothermal therapy (CDT, PDT and PTT) can be used to promoting tumor cell death by producing reactive oxygen species (ROS) or raising the temperature under irradiation or releasing the drug in response to stimulation of the tumor microenvironment (TME). This synergistic approach provides higher cancer ablation efficiency, lower therapeutic reagent demand and fewer side effects than individual therapeutic methods. Here, a multimodal intelligent nanoplatform (CuNCs-G/C@MOF-DOX) was constructed for tumor-specific, drug delivery and synergistic therapeutic applications, which integrates PTT, PDT and CDT via a cascade reaction triggered in the TME. The encapsulated CuNCs-G/C maintained the aggregated state, restricted the rotation of the ligands, and enhanced the photostability. Under light irradiation, CuNCs-G/C@MOF-DOX exhibited excellent PDT and PTT effects, further inducing cell apoptosis and pyroptosis. Additionally, localized temperature elevation promoted the enhancement of peroxidase-like activity to improve the CDT effect, inducing cell death. The issues of poor PDT efficacy caused by hypoxia in TME and insufficient CDT efficacy due to inadequate H2O2 levels were simultaneously addressed. Moreover, the drug DOX entered the cell nucleus to disrupt DNA structure for chemotherapy (CT). The released Cu2+ consumed the overexpressed glutathione (GSH) in tumor cells to produce Cu+, which effectively killed tumor for chemodynamic therapy (CDT). In vivo and vitro antitumor experiments further confirmed the excellent cell-killing ability (55.3%) of the multimodal nanoplatform. This study provides a rational approach for designing multimodal synergistic anti-tumor platforms, highlighting their potential for effective therapy.