Albumin-based co-loaded sonosensitizer and STING agonist nanodelivery system for enhanced sonodynamic and immune combination antitumor therapy.

STING agonists can activate natural and adaptive immune responses, and are expected to become a new type of immunotherapy drug for tumor therapy. However, how to target deliver STING agonists to tumor tissues is a key factor affecting the efficacy of tumor treatment. Sonodynamic therapy (SDT) has become a research hotspot in the field of cancer treatment due to its non-invasive, spatiotemporally controllable, and high tissue penetration capabilities. Therefore, how to choose the appropriate drug delivery strategy, build a suitable drug delivery system to co-deliver photosensitizers and STING agonists, is a challenge faced in the tumor treatment. In this study, we developed an albumin-based nanodelivery system named FA-ICG&MnOx@HSA that co-loaded the sonosensitizers indocyanine green (ICG) and manganese oxide (MnOx). This approach achieved folate receptor-targeting mediated tumor delivery and tumor microenvironment (TME)-responsive release facilitated by high levels of glutathione (GSH) and hydrogen peroxide (H2O2), which catalyze oxygen generation to potentiate SDT efficacy in killing tumors and inducing immunogenic cell death (ICD). Simultaneously, the released Mn2+ acted as a STING agonist promoting dendritic cell maturation, IFN-β production, and proliferation of T cells. Ultimately, this albumin based co-loaded sonosensitizer and STING agonist demonstrated promising potential for advancing tumor treatment.