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Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
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.
Abstract:
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide, with resistance to apoptosis being a major driver of therapeutic resistance and aggressive phenotype. This study aimed to develop a novel gene therapy approach for NSCLC by targeting resistance to apoptosis. Loss of function mutations of caspase 8 (CASP8) and downregulation of microRNAs (miRs) 29A-B1 and 34A were identified as key contributors to resistance to apoptosis in NSCLC. A biodegradable polymeric nano-gene delivery system composed of chitosan-poly-lactic-co-glycolic acid was formulated to deliver initiator CASP8 and miRs 29A-B1 and 34A. The nano-formulation efficiently encapsulated the therapeutic genes effectively internalized into NSCLC cells and induced significant apoptosis. Evaluation of the nano-formulation in A549 tumor spheroids showed a significant increase in apoptosis within the core of the spheroids, suggesting effective penetration into the spheroid structures. We provide a novel nano-formulation that demonstrate therapeutic potential for suicidal gene therapy in NSCLC.
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.
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