Manganese-doped biostimulatory nanoneedle for MRI-visual bispecific antibody gene delivery and immunosuppression reversal as a cancer immunotherapy strategy

Bispecific antibody (BsAb) is a new strategy being widely investigated in hematological cancer; however, its immunotherapy effect still exhibits poor prognosis in patients within solid tumors due to the rapid metabolism and short circulation in vivo. In this study, manganese oxide doped silicate nanosystem (Mn-MSN) was prepared for BsAb encoded minicircle DNA delivery. By transforming the Mn-MSN system's morphology from spherical to needle-like, it markedly improved gene transfection efficiency through the small "wounds" bio-stimulation, which was readily monitored by the magnetic resonance imaging and achieved high rate of antibody secre-tion for more than 5 days. This strategy also triggered the activation of cGAS-STING signaling pathway and redirected host lymphoid cells towards cancers. Therefore, a broad-spectrum T-cell responses was significantly enhanced in two kinds of immunologically cold solid tumors, resulted in potent anti-tumor immunotherapy. Our immunomodulation nanoplatform presented a powerful gene delivery vehicle that could directly activate native T cells, and gave a new insight into the development of genetic immunotherapy.