The PTT, SDT, and CDT synergistic antitumor effect of Fe3+-coordinated PDA@PLGA-Cur nanoparticles in vitro

Hepatocellular carcinoma (HCC) poses a severe threat to public health, with clinical therapy limited by narrow surgical indications, chemotherapeutic side effects, and targeted drug resistance. Herein, we developed Fe 3+ coordination Polydopamine@Poly (lactic-co-glycolic acid)-Curcumin (Fe 3+ -PDA@PLGA-Cur, FePPC) nanoparticles integrating photothermal therapy (PTT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), and curcumin (Cur)'s intrinsic anticancer activity for synergistic HCC treatment. FePPC was fabricated via emulsion solvent evaporation, in-situ dopamine polymerization, and Fe 3+ coordination chelation, with its structure and physicochemical properties characterized by FT-IR, UV-vis, SEM, XPS, and particle size analysis. FePPC exhibited uniform spherical morphology (198.58 nm), favorable stability, 73.60 ± 0.51% encapsulation efficiency, and NIR-triggered temperature-dependent Cur release. Under 808 nm NIR light (2 W/cm 2 , 4 cm), FePPC achieved a 24.4 °C temperature elevation with robust photothermal stability. Catalytic assays confirmed FePPC generated ·OH via Fe 3+ -mediated Fenton-like reactions, 1 O 2 under NIR irradiation, and ·O₂⁻ upon ultrasound stimulation, realizing synergistic reactive oxygen species (ROS) production. In vitro experiments on HepG2 cells showed time-dependent FePPC internalization; the FePPC + PTT + CDT + SDT group reduced cell viability to 53.45%, induced 47.55% apoptosis, elevated intracellular ROS, disrupted mitochondrial membrane potential, downregulated LDH, modulated Bax/Bcl-2 expression, and inhibited cell migration. This study highlights FePPC's potential as a multifunctional nanoplatform for HCC therapy via coordinated chemical-biological interactions.