High‐Efficiency Gold Nanoaggregates for NIR LED‐Driven Sustained Mild Photothermal Therapy Achieving Complete Tumor Eradication and Immune Enhancement

Abstract For millennia, humans have harnessed thermal energy to treat cancer. However, delivering energy to tumor tissues in traditional hyperthermia remains a significant challenge. Nanotechnology has revolutionized this approach, enabling nanomaterials to target tumors precisely and act as internal heat sources. Nanomaterial‐based photothermal therapy employs nano‐photothermal agents to absorb near‐infrared light and convert it into heat, offering non‐invasive, highly controllable, and specific treatment for solid tumors. Nonetheless, achieving complete tumor eradication, preventing recurrence, and ensuring safety continue to be major concerns. To address these issues, sustained mild photothermal therapy (smPTT) is proposed, utilizing gold nanoaggregates (AuNAs) with a high photothermal conversion efficiency (92.8%) in combination with a single irradiation of low‐power (∼0.1 W cm − 2 ) sustained LED light. This method achieved complete tumor eradication in animal models, with no recurrence over long‐term (>180 days) monitoring. This strategy provides superior therapeutic effects compared to mild photothermal therapy and higher safety than high‐temperature photothermal therapy. Additionally, it induces a strong immune response and immune memory, crucial for preventing tumor recurrence and metastasis. This novel approach to photothermal therapy may significantly impact clinical applications for shallow tumor treatment and offer new avenues for immunotherapy.