[P006] Poster

1:00 PM - 1:50 PM JST(4:00 AM - 4:50 AM UTC)

[P03-336] Tumor-Targeted Hyaluronic Acid/Tannic Acid-Engineered Oxygen Nanogenerators with IR780 Payloads Enable Dual-Mode Glutathione Depletion and Effective Singlet Oxygen Generation for Melanoma Treatment

○Wen-Hsuan Chiang¹, Chai-How Hsu¹, I-Ju Liu¹ (1. National Chung Hsing University (Taiwan))

Keywords:

Hyaluronic acid,Tumor-targeting oxygen nanogenerators,Dual-mode GSH consumption

Despite notable advances in combined photothermal (PTT) and photodynamic (PDT) therapy for melanoma, therapeutic efficacy is still constrained by tumor hypoxia, intracellular glutathione (GSH)-based antioxidation, poor tumor targeting, low photothermal conversion efficiency, and pronounced photobleaching of small-molecule photosensitizers. To overcome these hurdles, we engineered tumor-targeting and GSH self-depleting hyaluronic acid (HA)/tannic acid (TA)-engineered Prussian blue (PB) nanoparticles that function as oxygen nanogenerators (ONs) and carriers of the IR780 photosensitizer, thereby amplifying PTT/PDT-mediated melanoma treatment. The IR780-carrying HA/TA-coated PB (IHTPB) ONs were characterized as having a uniform cubic shape, stable colloidal dispersion, acidity/GSH-enhanced IR780 liberation, excellent PB/IR780-driven photothermal conversion efficiency (60%), and photothermal stability. Notably, the IHTPB ONs not only enabled dual-mode GSH depletion through PB-induced GSH oxidation combined with TA-driven GSH covalent conjugation, but also showed PB-mediated O₂ generation, thus producing abundant singlet oxygen (¹O₂) via the IR780-based photodynamic effect. Following CD44-mediated internalization by B16F10 melanoma cells, IHTPB ONs effectively consumed intracellular GSH, generated O₂, and, upon exposure to near-infrared irradiation, produced ¹O₂ and heat, resulting in mitochondrial dysfunction and lipid peroxidation to provoke apoptosis and ferroptosis. In comparison with free IR780 and non-HA-decorated ITPB ONs, the CD44-targeting IHTPB ONs achieved enhanced accumulation in B16F10 tumor tissues and more potent tumor growth suppression, resulting in improved mouse survival through boosted phototherapy driven by GSH self-depletion and relief of tumor hypoxia. This study presents a novel strategy for designing O₂ self-supplying and dual-mode GSH-depleting nanocarriers as tumor-targeted photosensitizer delivery systems to potentiate synergistic PTT/PDT-based melanoma treatment.