NIR Light Activated Polyphenol Driven Carrier-Free Self-Assembled Nanoparticles for Synergistic Chemo-PDT-PTT

ions serve as coordination bridges between apigenin and tannic acid, forming a stable metal-phenolic network that facilitates spontaneous nanoparticle self-assembly. The obtained AT-Cu NPs exhibited good aqueous dispersibility, uniform spherical morphology, an average diameter of approximately 120 nm, and favorable structural stability. Density functional theory calculations were used to support the proposed coordination interactions and preferred binding geometries within the AT-Cu framework. Owing to the abundant phenolic and carbonyl coordination sites, AT-Cu NPs enabled efficient loading and stabilization of the near-infrared (NIR) dye IR-820. IR@AT-Cu NPs demonstrated effective photothermal conversion efficiency and singlet oxygen generation under 808 nm irradiation. In vitro studies showed that IR@AT-Cu NPs significantly enhanced cancer cell killing under NIR irradiation through a synergistic combination of chemotherapy, photodynamic therapy, and photothermal therapy. Mechanistic investigations suggested that the induced cell death was mainly associated with mitochondria-dependent apoptosis. Overall, this work presents a simple, biocompatible, carrier-free nanotherapeutic strategy that integrates polyphenol chemistry, metal coordination, and NIR-responsive multimodal therapy for potential combination cancer treatment.