Noninvasively immunogenic sonodynamic therapy with manganese protoporphyrin liposomes against triple-negative breast cancer

Sonodynamic therapy (SDT) is a promising approach for tumor treatment because of the noninvasion, and future would be perfect while it activates systemic immune responses through deep penetration to effectively avoid tumor recurrence. Here, a multifunctional nanosonosensitizer system (FA-MnPs) is designed by encapsulating manganese-protoporphyrin (MnP) into folate-liposomes. The nanoparticles of FA-MnPs not only exhibit excellent depth-responsive SDT but also simultaneously activate SDT-mediated immune response. Under US irradiation, FA-MnPs show the high acoustic intensity in mimic tissue up to 8 cm depth and generate amount of singlet oxygen (1O2). Density functional theory (DFT) calculations reveal that metal coordination in MnP has enhanced the US response ability. The good depth-responsed SDT of FA-MnPs efficiently suppresses the growth of not only the superficial tumors but also the deep lesion in the triple-negative breast cancer (TNBC) mice model. Importantly, FA-MnPs-induced SDT further re-polarizes immunosuppressive M2 macrophages to antitumor M1 macrophages, and elicits immunogenic cell death (ICD) to activate dendritic cells, T lymphocytes, and natural killercells (NK), which consequently trigger the antitumor immune, contributing to the tumor growth inhibition. This study put forward an idea for curing deep-seated and metastatic tumors through noninvasively depth-irradiated immunogenic SDT by reasonably designing multifunctional sonosensitizers.