We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Enhanced Efficacy of Gastric Cancer Treatment through Targeted Exosome Delivery of 17-DMAG Anticancer Agent.
- Authors
Park, Jung Hyun; Kim, Say-June; Kim, Ok-Hee; Kim, Dong Jin
- Abstract
In this study, we explored the potential of genetically engineered exosomes as vehicles for precise drug delivery in gastric cancer therapy. A novel antitumor strategy using biocompatible exosomes (Ex) was devised by genetically engineering adipose-derived stem cells to express an MKN45-binding peptide (DE532) on their surfaces. 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) was encapsulated in engineered exosomes, resulting in 17-DMAG-loaded DE532 exosomes. In both in vitro and in vivo experiments using mouse gastric cancer xenograft models, we demonstrated that 17-DMAG-loaded DE532 Ex exhibited superior targetability over DE532 Ex, 17-DMAG-loaded Ex, and Ex. Administration of the 17-DMAG-loaded DE532 Ex yielded remarkable antitumor effects, as evidenced by the smallest tumor size, lowest tumor growth rate, and lowest excised tumor weight. Further mechanistic examinations revealed that the 17-DMAG-loaded DE532 Ex induced the highest upregulation of the pro-apoptotic marker B-cell lymphoma-2-like protein 11 and the lowest downregulation of the anti-apoptotic marker B-cell lymphoma-extra large. Concurrently, the 17-DMAG-loaded DE532 Ex demonstrated the lowest suppression of antioxidant enzymes, such as superoxide dismutase 2 and catalase, within tumor tissues. These findings underscore the potential of 17-DMAG-loaded DE532 exosomes as a potent therapeutic strategy for gastric cancer, characterized by precise targetability and the potential to minimize adverse effects.
- Subjects
STOMACH cancer; PEPTIDES; EXOSOMES; TUMOR growth; DRUG carriers
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 16, p8762
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25168762