RGD targeted magnetic ferrite nanoparticles enhance antitumor immunotherapeutic efficacy by activating STING signaling pathway
Guangyuan Shi, Xiaoli Liu, Yang Du, Jie Tian
Abstract
Manganese has been used in tumor imaging for their ability to provide T1-weighted MRI signal. Recent research find Mn 2+ 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 Mn 2+ often results in toxicity. In this study, we developed an RGD targeted magnetic ferrite nanoparticle (RGD-MnFe 2 O 4 ) 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-MnFe 2 O 4 showed active tumor targeting and longer accumulation at tumor sites. Moreover, RGD-MnFe 2 O 4 can activate STING pathway with low toxicity to enhance the PD-L1 expression. Furthermore, combining RGD-MnFe 2 O 4 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.