A CD44‐Targeted TLR7/8 Nanovaccine for Synergistic Photothermal Immunotherapy

ABSTRACT Cancer continues to remain challenging due to heterogeneity and therapeutic resistance. Conventional therapeutic approaches, such as surgery, chemotherapy, and radiotherapy, often encounter critical limitations such as extensive tissue damage and ineffective elimination of metastatic malignancies. To resolve these issues, nanomaterial‐based therapeutics have progressed to develop improved anticancer treatment outcomes. In this context, a CuS‐R848‐mediated therapeutic nanovaccine (NV) for synergizing photothermal therapy (PTT) with TLR7/8‐driven immunity has been developed. To improve the stability and specificity, the NV was systematically coated with hyaluronic acid (HA) to effectively target and reduce systemic toxicity via CD44‐targeted delivery. Furthermore, the NV under near‐infrared (NIR) light exhibited 98% tumor ablation, including immunogenic cell death (ICD) induction via DAMPs, DC maturation, and significantly enhanced tumor eradication to strengthened immune activation. This dual‐approach combining PTT with ICD demonstrated excellent therapeutic vaccine efficacy in preventing tumor recurrence and metastasis compared to monotherapy.