Cancer Cell Membrane Camouflaged Mesoporous Silica Nanoparticles Combined with Immune Checkpoint Blockade for Regulating Tumor Microenvironment and Enhancing Antitumor Therapy

Int J Nanomedicine. 2021 Mar 12;16:2107-2121. doi: 10.2147/IJN.S295565. eCollection 2021.

Abstract

Purpose: Although anti-programmed cell death protein 1 antibody (aPD1) immunotherapy and chemotherapy has made much progress in the treatment of melanoma, the efficacy still needs to be further improved.

Methods: Cancer treatment has been greatly enhanced by the use of nanotechnology. Cancer cell membrane (CCM)-camouflaged nanoparticles have shown promising potential in tumor therapy due to their excellent homologous-targeting ability, long blood circulation and immune escape. This work presents a biocompatible and tumor acidic environmental responsive CCM-camouflaged mesoporous silica nanoparticle (CMSN) that is loaded with dacarbazine (DTIC) and combined with aPD1 to achieve better antitumor efficacy.

Results: In vitro cell experiments demonstrated that DTIC@CMSN exhibits a better anti-tumor killing efficiency and a stronger ability to promote the apoptosis of tumor cells than free DTIC. In vivo antitumor results demonstrated that combination therapy of DTIC@CMSN chemotherapy and aPD1 immunotherapy remarkably suppress the melanoma growth and prolong survival time due to highly selective tumor killing, activation of tumor-specific T cells, and regulation of the immunosuppressive tumor microenvironment. In addition, safety evaluation studies of DTIC@CMSN also demonstrate their increased tumor accumulation and decreased systemic toxicity.

Conclusion: This study provides a promising nano-platform for the combination of chemotherapy with immunotherapy, which is potentially useful for the treatment of melanoma.

Keywords: anti-PD-1; cancer cell membrane; cancer immunotherapy; melanoma; mesoporous silica nanoparticle.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Death / drug effects
  • Cell Membrane / pathology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Combined Modality Therapy
  • Dacarbazine / pharmacology
  • Dacarbazine / therapeutic use
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology*
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Particle Size
  • Porosity
  • Silicon Dioxide / chemistry*
  • Static Electricity
  • Tumor Microenvironment / drug effects*

Substances

  • Antineoplastic Agents
  • Immune Checkpoint Inhibitors
  • Silicon Dioxide
  • Dacarbazine