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

Abstract

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.

Keywords: Immunotherapy; Responsive drug release; SDT; STING agonist.