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

Jiali Li,Zhen Li,Yaqi Shen,Yang Peng,Zhiping Zhang,Shichao Li,Guanjie Yuan,Yang Li,Li Kong,Conglian Yang

doi:10.1186/s12951-021-01158-y

Abstract

BackgroundImmunochemotherapy 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 resultsHerein, 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.ConclusionsThis kind of therapeutic strategy that combined MnP@Lip nanoparticles with platinum-based chemotherapeutics may provide a novel insight for immunochemotherapy.Graphical

Highlights

Global Cancer Statistics 2020 indicated that cancer was the greatest cause of human deaths, and this warned us that the pace of cancer prevention and treatment must be accelerated [1]
Through in-depth study on the stimulator of interferon genes (STING) activation mechanism of M n2+, we found that Mn2+ could better activate the downstream pathway
After 24 h, the supernatant was collected to test the production of IFN-β, and the cells were harvested to examine the CD80 expression level by a flow cytometer. Another group of bone marrow derived macrophage (BMDM) cells (2 × 106 cells/well, 6-well plate) that were treated with MnCl2 (0, 50, 100, 200 and 400 μM) were lysed to obtain protein, and the expression of cGAS, pSTING/STING, pNF-кB p65/NF-кB p65 and pIRF3/ IRF3 were tested by western blot

Summary

Methods and results

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 M n2+ 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. Anti-tumor experiments in vivo proved that MnP@Lip combined with platinumbased chemotherapeutics increased T cells infiltration in the tumor microenvironment, and inhibited tumor growth in the orthotopic therapeutic and postoperative tumor models

Conclusions

Introduction

Materials and methods

Results and discussion

Conclusion

Global Cancer Statistics 2020