RGD targeted magnetic ferrite nanoparticles enhance antitumor immunotherapeutic efficacy by activating STING signaling pathway

Manganese has been used in tumor imaging for their ability to provide T1-weighted MRI signal. Recent research find Mn²⁺ can induce activation of the stimulator of interferon gene (STING) pathway to create an active and favorable tumor immune microenvironment. However, the direct injection of Mn²⁺ often results in toxicity. In this study, we developed an RGD targeted magnetic ferrite nanoparticle (RGD-MnFe₂O₄) to facilitate tumor targeted imaging and improve tumor immunotherapy. Magnetic resonance imaging and fluorescence molecular imaging were performed to monitor its in vivo biodistribution. We found that RGD-MnFe₂O₄ showed active tumor targeting and longer accumulation at tumor sites. Moreover, RGD-MnFe₂O₄ can activate STING pathway with low toxicity to enhance the PD-L1 expression. Furthermore, combining RGD-MnFe₂O₄ and anti-PD-L1 antibody (aPD-L1) can treat several types of immunogenic tumors through promoting the accumulation of tumor-infiltrating cytotoxic T cells. In general, our study provides a promising new strategy for the targeted and multifunctional theranostic nanoparticle for the improvement of tumor immunotherapy.