PtTe2-alginate hydrogels for combined photothermal-chemodynamic cancer therapy by inducing cell apoptosis via modulation of TNF-α-related signaling pathways

Head and neck squamous cell carcinoma ranks as the sixth most common malignant tumor worldwide, with the majority of cases manifesting as oral squamous cell carcinoma (OSCC). The current clinical standard for treating OSCC consists of surgical resection followed by radiotherapy and chemotherapy. This multimodal approach, however, is associated with substantial morbidity, significant perioperative risk, and frequent systemic toxicities that markedly impair quality of life. Therefore, novel, more effective, and safer treatment strategies are urgently needed. Here, PtTe₂ nanorods were synthesized and encapsulated in sodium alginate (ALG) to form a novel injectable hydrogel for the precise treatment of OSCC. This ALG hydrogel prolongs the intratumoral retention of PtTe₂, ensuring sustained local availability. PtTe₂ exhibits tumor microenvironment-responsive catalytic activity, catalyzing the conversion of hydrogen peroxide into highly toxic hydroxyl radicals via Fenton-like reactions. Moreover, PtTe₂ possesses exceptional photothermal conversion efficiency, enabling precise, light-driven hyperthermia that selectively and effectively ablates tumor cells. By synergistically accelerating the kinetics of Fenton-like reactions through photothermal effects, the generation of reactive oxygen species is substantially amplified, effectively overwhelming the antioxidant defense system and achieving significant antitumor effects. Both <i>in vitro</i> and <i>in vivo</i> experiments demonstrated that the PtTe₂ <b>-</b>ALG hydrogel achieved robust antitumor efficacy and excellent biosafety. Transcriptomic analyses revealed significant activation of apoptosis-related signaling cascades, elucidating the molecular mechanism of PtTe₂ <b>-</b>based tumor therapy. By combining chemodynamic and photothermal therapy within a single, injectable platform, this work provides a promising, low-toxicity strategy for the clinical management of OSCC.