Apoptosis-targeted gene therapy for non-small cell lung cancer using chitosan-poly-lactic-co-glycolic acid -based

Sourav Chattopadhyay1, Shashanka Shekhar Sarkar1, Sheetanshu Saproo1

  • 1Department of Biomedical Engineering, Indian Institute of Technology Ropar, Rupnagar, Punjab, India.

Insights

This study developed a novel nano-gene therapy for non-small cell lung cancer (NSCLC) by delivering caspase 8 and specific microRNAs to induce apoptosis and overcome therapeutic resistance.

Area of Science:

  • Oncology
  • Nanotechnology
  • Gene Therapy

Background:

  • Non-small cell lung cancer (NSCLC) exhibits resistance to apoptosis, contributing to therapeutic failure and aggressive disease.
  • Caspase 8 (CASP8) loss-of-function mutations and reduced miR-29A-B1/miR-34A levels are key mechanisms driving apoptosis resistance in NSCLC.

Purpose of the Study:

  • To develop a novel nano-gene delivery system for NSCLC targeting apoptosis resistance.
  • To deliver initiator CASP8 and specific microRNAs (miRs 29A-B1 and 34A) to NSCLC cells.

Main Methods:

  • Formulation of a biodegradable polymeric nano-gene delivery system using chitosan-poly-lactic-co-glycolic acid.
  • Encapsulation and delivery of CASP8 and miRs 29A-B1/34A into NSCLC cells.
  • Evaluation of nano-formulation efficacy in A549 tumor spheroids.

Main Results:

  • The nano-formulation efficiently encapsulated and delivered therapeutic genes into NSCLC cells.
  • Significant induction of apoptosis was observed in NSCLC cells treated with the nano-formulation.
  • Effective penetration and apoptosis induction within the core of A549 tumor spheroids were demonstrated.

Conclusions:

  • A novel nano-formulation shows therapeutic potential for NSCLC.
  • This approach offers a promising strategy for suicidal gene therapy in NSCLC by overcoming apoptosis resistance.