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Reshaping Tumor Immune Microenvironment through Acidity-Responsive Nanoparticles Featured with CRISPR/Cas9-Mediated

Kun Tu1, Huan Deng1,2, Li Kong1

  • 1Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

ACS Applied Materials & Interfaces
|March 21, 2020
PubMed

Insights

This study developed novel nanoparticles to transform "cold" tumors into "hot" tumors for enhanced cancer immunotherapy. The treatment significantly inhibited tumor growth and improved survival rates.

Area of Science:

  • Biomedical Engineering
  • Cancer Immunotherapy
  • Nanotechnology

Background:

  • Cancer immunotherapy faces challenges due to the immunosuppressive "cold" tumor microenvironment.
  • Monoclonal antibodies targeting immune checkpoints show promise but are limited by this microenvironment.

Purpose of the Study:

  • To develop acidity-responsive nanoparticles co-loaded with CRISPR/Cas9 and paclitaxel (PTX) to convert "cold" tumors into "hot" tumors.
  • To enhance the efficacy of cancer immunotherapy by overcoming the limitations of the tumor microenvironment.

Main Methods:

  • Co-loading CRISPR/Cas9 and paclitaxel (PTX) into weak acidity-responsive nanoparticles.
  • Utilizing CRISPR/Cas9 to knock out the cyclin-dependent kinase 5 gene, reducing programmed death-ligand 1 expression.
  • Employing PTX to induce immunogenic cell death, modulate immune cells, and enhance antitumor immunity.

Main Results:

  • Nanoparticles demonstrated high cargo capacity, efficient transfection, biocompatibility, and tumor accumulation.
  • CRISPR/Cas9 effectively reduced programmed death-ligand 1 expression on tumor cells.
  • Combined therapy significantly inhibited tumor growth and prolonged overall survival from 16 to 36 days.

Conclusions:

  • The developed nanoparticles effectively convert "cold" tumors to "hot" tumors, enhancing combinatorial immunotherapy and chemotherapy.
  • This strategy offers a promising approach for overcoming the limitations of current cancer immunotherapies.
  • The research provides a valuable reference for developing novel cancer treatment strategies.
Keywords:
CRISPR/Cas9PD-L1immunochemotherapyimmunogenic cell deathnanoparticle

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