NIR II light-driven nanomotor synergistically enhances immunogenic cell death through photothermal and chemodynamic therapy for melanoma immunotherapy

Melanoma is a highly invasive and metastatic malignant skin tumor. Recently, immunogenic cell death (ICD) has attracted great attention as a promising approach to immunotherapy. However, efficiently and comprehensively activating ICD throughout the dense tumor tissue is a key challenge. Herein, we designed a NIR II light-driven asymmetric nanomotor drug delivery system (Sor@CS-ZIF-8@MO1) to achieve deep penetration into the tumor tissue. By combining photothermal therapy (PTT) and chemodynamic therapy (CDT) to synergistically induce ICD, the immunotherapeutic efficacy against melanoma is enhanced. The research results showed that Sor@CS-ZIF-8@MO1 exhibited good photothermal performance and motor-driven performance, and was able to effectively penetrate 3D tumor cell spheroids deeply. Sor@CS-ZIF-8@MO1 targeted tumor tissues through mannose and controllably released sorafenib under the low pH conditions in tumor tissues and photothermal stimulation, thereby promoting tumor tissue angiogenesis to improve its hypoxic microenvironment and effectively enhancing the CDT effect induced by Cu^+/2+. This could synergistically enhance the ICD of tumor cells with the PTT. Meanwhile, the tumor-associated antigens released by ICD, together with ovalbumin and mannose, stimulated immune response, reshaped the tumor immune microenvironment, enhanced tumor immunity, and ultimately effectively inhibited the growth and metastasis of melanoma tumors. In this work, a nanomotor delivery system that integrates multiple modalities and is capable of deeply penetrating tumor tissues to efficiently and comprehensively induce immunogenic cell death (ICD) has been designed, providing a new strategy to address the problem of insufficient induction of ICD in melanoma immunotherapy.