Exosome-Mediated RUNX3 DNA Delivery for Lung Cancer Therapy

Area of Science:

• Biomedical Engineering
• Oncology
• Gene Therapy

Background:

• Lung cancer gene therapy faces challenges in delivery, targeting, and safety.
• Exosomes offer biocompatible and cancer-cell-targeting delivery potential.

Purpose of the Study:

• To develop and evaluate exosome-mediated RUNX3 gene therapy for lung adenocarcinoma.
• To assess the safety and efficacy of RUNX3-loaded exosomes (hExo-Rs) in vitro and in cancer spheroids.
• To create a hydrogel platform for sustained release of hExo-Rs.

Main Methods:

• Packaging RUNX3 plasmid DNA into human exosomes (hExo-Rs).
• Evaluating hExo-Rs' effect on lung cancer cell viability and apoptosis.
• Assessing hExo-Rs' impact on normal fibroblast viability.
• Analyzing cytokine-induced M1 macrophage polarization post-treatment.
• Developing a gelatin hydrogel for 14-day sustained release of hExo-Rs.

Main Results:

• hExo-Rs decreased cancer cell viability to 43.3% while normal fibroblasts remained at 96.0% viability.
• Treated cancer cells released cytokines that promoted M1 macrophage polarization.
• The hydrogel platform enabled targeted, 14-day sustained release of RUNX3 pDNA.
• Selective decrease in cancer cell viability and confirmed apoptosis were observed with the hydrogel system.

Conclusions:

• Exosome-mediated RUNX3 gene therapy demonstrates selective anticancer effectiveness.
• The developed hydrogel platform facilitates localized, sustained release for potential clinical translation.
• This approach shows promise for safe and effective lung cancer treatment and immunotherapy.