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Using In Vitro Live-cell Imaging to Explore Chemotherapeutics Delivered by Lipid-based Nanoparticles
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Deformable liposomal codelivery of vorinostat and simvastatin promotes antitumor responses through remodeling tumor

Bin Tu1, Yang He, Binfan Chen

  • 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai 201203, China. yzhuang@simm.ac.cn.

Biomaterials Science
|November 10, 2020
PubMed

Insights

This study developed a novel deformable liposome system for delivering epigenetic drugs to remodel the tumor microenvironment in non-small cell lung cancer. The treatment effectively inhibited tumor growth by reprogramming macrophages and enhancing anti-tumor immunity.

Area of Science:

  • Oncology
  • Nanomedicine
  • Immunology

Background:

  • The tumor microenvironment (TME) and tumor-associated macrophages (TAM) are critical in non-small cell lung cancer (NSCLC) progression.
  • Epigenetic therapies offer potential for TME remodeling, but effective drug delivery remains a challenge.

Purpose of the Study:

  • To develop a deformable liposome (D-Lipo) system for codelivering vorinostat and simvastatin.
  • To investigate the efficacy of D-Lipo in a chemo-free therapeutic strategy for NSCLC by remodeling the TME.

Main Methods:

  • Formulation of deformable liposomes for dual drug delivery.
  • Evaluation of D-Lipo's intratumor infiltration and anti-tumor efficacy in xenografted lung tumors.
  • Analysis of immune cell populations (TAMs, CD8+ T cells, Tregs) and angiogenesis within the TME.

Main Results:

  • D-Lipo demonstrated enhanced intratumor infiltration and inhibited xenografted lung tumor growth.
  • The therapy successfully repolarized TAMs from M2 (pro-tumor) to M1 (anti-tumor) phenotype.
  • Significant reduction in pro-tumor M2 macrophages and regulatory T cells (Tregs), alongside an increase in anti-tumor M1 macrophages and CD8+ T cells, indicating TME remodeling and anti-angiogenesis.

Conclusions:

  • Deformable liposomes provide an effective platform for epigenetic drug codelivery, enabling chemo-free cancer therapy.
  • This strategy shows promise for remodeling the tumor microenvironment and enhancing anti-tumor immunity in solid tumors like NSCLC.

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