Jeon, Jieun Byun, Hayeon Lee, Myung Chul Kim, Jiseong Park, Seung Gwa Madrigal-Salazar, Andrea D. González, Montserrat L. Lopez-Pacheco, Mariana C. Liu, Wenpeng Nasr, Mahmoud L. Lee, Soo-Hong Lee, You-Soub Lee, Luke P. Kim, Woo-Jin Kim, Dohun Shin, Su Ryon 2025-12-04T06:30:23Z 2025-12-04T06:30:23Z 2025-12-03 2025-12 1944-8244 https://pubs.kist.re.kr/handle/201004/153742 Gene therapy represents a promising strategy for treating lung cancer, with the potential to inhibit the proliferation of cancerous cells and induce apoptosis. However, current gene therapy for lung cancer encounters challenges with delivery, targeting, and safety, such as off-target effects, immune responses, and the necessity for better delivery methods. Here, we introduce gene therapy using the key regulator in lung adenocarcinoma, runt-related transcription factor 3 (RUNX3), within exosomes (Exos), which are known for their biocompatibility and ability to selectively target cancer cells. We packaged the RUNX3 plasmid DNA into human exosomes (hExo-Rs), designed to target and induce apoptosis in cancer cells, resulting in a viability decrease to 43.3%. Normal fibroblasts remained viable at 96.0%, confirming the safety of hExo-Rs for future therapies. We delivered hExo-Rs to cancer spheroids, examined their effects, and found that cytokines from treated cells promote M1 macrophage polarization, emphasizing their potential for immunotherapy. We developed a hydrogel platform for the targeted 14-day release of RUNX3 pDNA by attaching hExo-Rs to gelatin using microbial transglutaminase, which enables the selective decrease in cancer cell viability and confirms apoptosis. Our demonstration of RUNX3 gene therapy with Exos presents selective anticancer effectiveness and the promise of clinical use through localized, sustained release using the hydrogel. English American Chemical Society Exosome-Mediated RUNX3 DNA Delivery for Lung Cancer Therapy Article 10.1021/acsami.5c15987 1 ACS Applied Materials & Interfaces, v.17, no.49, pp.66339 - 66357 ACS Applied Materials & Interfaces 17 49 66339 66357 N scie scopus 001628382300001 Nanoscience & Nanotechnology Materials Science, Multidisciplinary Science & Technology - Other Topics Materials Science Article GENE-THERAPY CELLS HYDROGELS GELATIN SOCIETY TISSUES exosome cancer spheroid immunomodulation hydrogel-basedlocal delivery cancer gene therapy lung cancer