Boosting immunotherapy of triple negative breast cancer through the synergy of mild PTT and Fe-loaded organosilica nanoparticles

Abstract

Triple negative breast cancer (TNBC) is associated with drug resistance, metastasis, and poor immune response. The development of novel strategies to evoke a robust immune response against TNBC is necessary. In this study, we propose a TNBC tumor immunotherapy modality by synergizing nanocatalytic medicine with mild photothermal therapy. Briefly, mesoporous organosilica nanoparticles (MONs) and an Fe³⁺-loaded MON (MOF) were prepared. Then, the MOF was modified by hyaluronic acid (HA) and loaded with indocyanine green (ICG) to obtain MOFH (IMOFH). The IMOFH was spherical with a uniform particle size and showed pH-dependent Fe³⁺ release behavior. In vitro experiments showed that IMOFH was effectively internalized by 4T1 cells, which resulted in Fe³⁺-mediated oxidative cell death in synergy with mild PTT. Furthermore, this synergistic therapy activated dendritic cells (DCs) through damage-associated molecular pattern (DAMP) exposure resulting from enhanced oxidative damage in tumor cells. In vivo experiments showed that the application of mild PTT promoted IMOFH-mediated maturation of DCs and infiltration of CD8⁺ T cells. The synergistic effects of IMOFH and mild PTT resulted in boosted activation of adaptive immunity. The pH responsive nanocatalytic medicine IMOFH promoted significant adaptive immunity through the exposure of tumor associated antigens via the Fe³⁺ mediated Fenton reaction in concert with mild PTT. These effects resulted in the elimination of TNBC tumors without obvious side effects. Therefore, such a synergistic modality of IMOFH + mild PTT is promising for TNBC therapy.