Biomimetic platelet membrane-engineered nanoplatforms for self-reinforcing ferroptosis-PDT synergy in oral tongue squamous cell carcinoma.

Oral tongue squamous cell carcinoma (OTSCC), characterized by aggressive progression and limited therapeutic efficacy, urgently demands innovative strategies to circumvent surgical morbidity and hypoxia-driven resistance. To address this, we developed platelet membrane -cloaked P@Ce6-AS nanoparticles, co-assembling artesunate (AS, ferroptosis inducer) and chlorin e6 (Ce6, photosensitizer) for synergistic ferroptosis-photodynamic therapy (PDT). Platelet membrane coating endowed P@Ce6-AS with CD47-mediated immune evasion and P-selectin/CD44-targeted delivery, achieving uniform morphology, pH-responsive drug release, and lysosome-triggered payload liberation. In vitro, P@Ce6-AS exhibited 4.95-fold higher tumor cell uptake than free Ce6 and Ce6-AS, with deep spheroid penetration. P@Ce6-AS exerted potent antitumor activity by orchestrating a multifaceted cytotoxic response, synergistically inducing GPX4-mediated ferroptotic lipid peroxidation and mitochondrial apoptosis to profoundly suppress CAL-33 cell viability. Collectively, this biomimetic nanoplatform demonstrates significant potential for clinical translation by overcoming hypoxia-driven therapeutic resistance while minimizing off-target toxicity, offering a paradigm shift in precision OTSCC management.