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Combating Cancer Stem-Like Cell-Derived Resistance to Anticancer Protein by Liposome-Mediated Acclimatization

Shiyang Shen1, Shiqi Lin1, Yuying Chen1

  • 1State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.

Nano Letters
|March 7, 2022
PubMed

Insights

This study introduces a novel liposome strategy to overcome cancer stem-like cell (CSC) resistance to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) therapy. The system sensitizes resistant CSCs to TRAIL-induced apoptosis, offering a promising approach for cancer treatment.

Area of Science:

  • Biomedical Engineering
  • Cancer Biology
  • Drug Delivery Systems

Background:

  • Antibody-based therapeutics offer targeted cancer apoptosis induction.
  • Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) activates apoptosis via death receptors (DRs).
  • Cancer stem-like cells (CSCs) exhibit resistance to TRAIL due to deficient DR expression.

Purpose of the Study:

  • To develop a strategy to overcome TRAIL resistance in CSCs.
  • To sensitize CSCs to TRAIL-mediated apoptosis.
  • To inhibit CSC-enriched tumor growth.

Main Methods:

  • Liposomal co-delivery of plasmid DNA encoding TRAIL and salinomycin.
  • Utilizing liposomes to engineer cancer cells into TRAIL protein generators.
  • Employing salinomycin to upregulate DR expression on CSCs, sensitizing them to TRAIL.

Main Results:

  • The liposomal system successfully enabled cancer cells to express TRAIL.
  • Salinomycin treatment upregulated DR expression on CSCs, enhancing TRAIL sensitivity.
  • Demonstrated efficient elimination of CSCs and inhibition of CSC-enriched tumor growth in an orthotopic colon tumor mouse model.

Conclusions:

  • A liposome-mediated acclimatization strategy effectively overcomes CSC-mediated TRAIL resistance.
  • This programmable drug co-delivery system holds potential for targeting CSCs.
  • The approach shows promise for improving cancer therapy efficacy by targeting resistant CSC populations.
Keywords:
anticancer proteincancer stem-like celldrug deliveryliposomeresistance

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