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

Guangyuan Shi; Xiaoli Liu; Yang Du; Jie Tian

doi:10.1016/j.isci.2024.109062

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

iScience. 2024 Feb 1;27(5):109062. doi: 10.1016/j.isci.2024.109062. eCollection 2024 May 17.

Authors

Guangyuan Shi^{1

2}, Xiaoli Liu³, Yang Du^{2

4}, Jie Tian⁵

Affiliations

¹ University of Science and Technology of China, Hefei 230026, China.
² CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
³ Northwest University, Xi'an 710127, China.
⁴ University of Chinese Academy of Sciences, Beijing 100080, China.
⁵ Science and Engineering, Beihang University, Beijing 100191, China.

Abstract

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.

Keywords: Biomedical materials; Biotechnology; Nanotechnology.