NIR-II photothermal therapy mediated by polymer-based nanoparticles to enhance checkpoint inhibitor immunotherapy for inhibiting lymph node metastasis in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC), a prevalent malignancy with high recurrence and metastasis rates, poses significant treatment challenges, particularly the prevention of lymph node metastasis. The development of a powerful photothermal agent for combined photothermal immunotherapy that inhibits OSCC metastasis remains challenging. Our study introduces an approach utilizing nanoparticles synthesized from a novel polymer with strong electron donor-acceptor structures for Near-Infrared II (NIR-II) photothermal therapy (PTT) by increasing intermolecular π-π interactions and enhancing non-radiative transitions. Owing to the superior tissue penetration capabilities of NIR-II region, these nanoparticles exhibit exceptional photothermal conversion, stability, and biocompatibility, making them ideal for deep-seated tumor ablation with minimal off-target effects. Mechanistically, the RNA-sequencing analysis revealed the upregulation of crucial apoptosis-related and antigen-presenting pathways in PTT-treated cancer cells. Polymer nanoparticles can intensify the immunogenic cell death to elicit a tumor-related immune response, releasing dramatically tumor-associated antigens, and activating damage-associated molecular patterns to eliminate tumor cells synergistically. As evidenced by our comprehensive in vivo OSCC mouse model, subsequent detailed approaches further demonstrated significant cancer cell eradication and induction of a strong immunogenic response to inhibit lymph node metastasis. Our study highlights the potential of tumor cell ablation and immunogenic activation dual therapy for targeting both primary and metastatic OSCC, suggesting a new direction for reshaping current therapeutic strategies for OSCC treatment.