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

J Nanobiotechnology. 2021 Dec 11;19(1):415. doi: 10.1186/s12951-021-01158-y.

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.

Keywords: Anti-tumor; Immunochemotherapy; Manganese; Platinum-based chemotherapeutics; STING activation.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacokinetics
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cells, Cultured
  • Female
  • Immunotherapy
  • Macrophages / drug effects
  • Magnetic Resonance Imaging
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Molecular Probes* / chemistry
  • Molecular Probes* / pharmacokinetics
  • Nanoparticles* / chemistry
  • Nanoparticles* / metabolism
  • Neoplasms, Experimental
  • Platinum* / chemistry
  • Platinum* / pharmacokinetics
  • Platinum* / pharmacology
  • Tumor Microenvironment / drug effects

Substances

  • Antineoplastic Agents
  • Membrane Proteins
  • Molecular Probes
  • STING1 protein, human
  • Platinum