A biomimetic manganese-phycocyanin nanodrug-carrying system and its sonodynamic-immunological anti-tumor therapy

Cutaneous melanoma is characterized by malignant proliferation, high aggressiveness, high metastasis, rapid recurrence, and low survival rate; therefore, research on its treatment is vital. In this study, a novel nano system combining sonodynamics and immunotherapy for cutaneous melanoma treatment was designed and developed. Based on the use of phycocyanin for the biomineralization of manganese ions, smart and multifunctional manganese phycocyanin nanoparticles encapsulating the immune adjuvant levamisole (LMS) with melanoma B16-OVA cell membranes wrapped around its outer layer (Mn-PCNP-LMS@CM) were designed and prepared. The experimental results showed that Mn-PCNP-LMS@CM efficiently targeted cutaneous melanomas. Under ultrasonic excitation, it catalyzed oxygen production from hydrogen peroxide in the tumor environment, reduced high glutathione levels in tumor tissues, and significantly enhanced (reactive oxygen species) ROS generation, thus improving the outcome of sonodynamic therapy. In contrast, sonodynamic therapy induced immunogenic death of tumor cells, together with the loaded immune adjuvant levamisole, which promoted the maturation of dendritic cells (DCs), modulated the immunosuppressive microenvironment, enhanced the immunotherapeutic effect, and stimulated the function of long-term immune memory to prevent tumor growth and recurrence. This study is expected to provide new ideas for developing novel anti-tumor nano systems and achieving anti-tumor synergistic therapy.