Hyperthermia-Accelerated Ion-Radical Production for Enhanced Tumor Nanocatalytic Therapy with Inhibition of Tumor Growth and Recurrence.

Abstract

Breast cancer is a significant health concern for women, and traditional chemotherapy, while effective, comes with harsh side effects and high recurrence rates. This necessitates the exploration of alternative therapeutic strategies. Photothermal therapy (PTT) offers a promising alternative, but its limited penetration depth hinders its efficacy in deeper tumors. This study designs a photothermal-enhanced nanocatalytic medicine, AF@mPDA@HA, that combines the advantages of PTT and nanocatalytic medicine to improve therapeutic outcomes. The system utilizes mesoporous polydopamine (mPDA) as a photothermal agent and a carrier of iron ions (Fe³⁺) and ammonium persulfate (APS), while hyaluronic acid (HA) provides a protective coating to prevent premature drug release and improve targeting to tumor tissues. APS shows higher affinity and reaction rate with ferrous ion than H₂O₂, as alternative of H₂O₂ as catalytic medicine. Once AF@mPDA@HA accumulated at the tumor site, PTT-induced hyperthermia promotes released APS and Fe³⁺ penetration into the deep tumor. The presence of reduced glutathione (GSH) in tumor converts iron ions to ferrous ions, which then react with APS to produce sulfate radicals (SO₄^-•). The photothermal effect further expedites this reaction, boosting the overall therapeutic efficacy. This multifunctional nanoplatform overcomes the limitations of current treatments and provides an ideal advancement in breast cancer therapy.