A magnetic resonance nanoprobe with STING activation character collaborates with platinum-based drug for enhanced tumor immunochemotherapy

Abstract

Background Immunochemotherapy is a potent anti-tumor strategy, however, how to select therapeutic drugs to enhance the combined therapeutic effect still needs to be explored. Methods and results Herein, a magnetic resonance nanoprobe (MnP@Lip) with STING (Stimulator of INterferon Genes) activation character was synthesized and co-administered with platinum-based chemotherapeutics for enhanced immunochemotherapy. MnP@Lip nanoparticles was prepared by simple fabrication process with good reproducibility, pH-sensitive drug release behavior and biocompatibility. In vitro experiments elucidated that Mn2+ can promote the polarization of M0 and/or M2 macrophages to M1 phenotype, and promote the maturation of BMDC cells. Upon Mn2+ treatment, the STING pathway was activated in tumor cells, mouse lung epithelial cells, and immune cells. More importantly, anti-tumor experiments in vivo proved that MnP@Lip combined with platinum-based chemotherapeutics increased T cells infiltration in the tumor microenvironment, and inhibited tumor growth in the orthotopic therapeutic and postoperative tumor models. Conclusions This kind of therapeutic strategy that combined MnP@Lip nanoparticles with platinum-based chemotherapeutics may provide a novel insight for immunochemotherapy. Graphical Abstract

Recent progress on the activation of the cGAS–STING pathway and its regulation by biomolecular condensation

“…Moreover, in patients with advanced metastatic solid tumors who failed in standard anticancer treatments such as chemotherapies, radiotherapy, and immunotherapies, Mn 2+ administration exhibits a notably improved therapeutic efficacy with 45.5% objective response and 90.9% disease control ( Lv et al., 2020 ). Significantly, similar enhanced antitumor effects by Mn 2+ -promoted cGAS–STING activation in various antitumor immunotherapies have been reported ( Hou et al., 2020 ; Chen et al., 2021 ; Gao et al., 2021 ; Li et al., 2021a ; Liu et al., 2021 ; Song et al., 2021 ; Sun et al., 2021a ; Wang et al., 2021a ; Yang et al., 2021 ; Yi et al., 2021 ). Considering the component simplicity and steadiness of Mn 2+ , Mn 2+ treatment or combined antitumor therapies including immunotherapies may have promising clinical potential.…”