Safe and efficient treatment of drug-resistant colorectal cancer cells using kaempferol-loaded exosomes

• Published in: Biotechnology and bioprocess engineering 2024, 29(6), , pp.1108-1117
• Main Authors: Min, Jun, Jeung, Dohyun, Lee, Dae Gyun, Kang, Hyeon Ju, Jo, Ha Young, Tram, Le Thi Hong, Kang, Han Chang, Lee, Joo Young, Lee, Hye Suk, Rhee, Won Jong, Kim, Byoung Choul, Cho, Yong-Yeon, Shim, Min Suk
• Format: Article
• Language: English
• Subjects: antineoplastic activity; Antitumor activity; Bioavailability; Biotechnology; Cancer; Cell cycle; cell cycle checkpoints; Cell proliferation; Chemistry; Chemistry and Materials Science; Chemotherapy; Colorectal cancer; Colorectal carcinoma; colorectal neoplasms; Cyclin-dependent kinase inhibitor p21; Drug resistance; drug therapy; drugs; Exosomes; Flavonols; GTP-binding protein; Industrial and Production Engineering; Kaempferol; Load resistance; nanocarriers; Oxaliplatin; Plant cells; Research Paper; Resistance factors; Side effects; 생물공학
• ISSN: 1226-8372; 1976-3816
• DOI: 10.1007/s12257-024-00160-z

Drug resistance to chemotherapy is a primary factor contributing to recurrence in colorectal cancer patients. Therefore, the development of new chemotherapeutic strategies capable of overcoming drug resistance while minimizing side effects is crucial. Kaempferol (KF), a natural flavonol derived from plants, exhibits potential in overcoming drug resistance in colorectal cancer cells but suffers from low bioavailability. In this study, exosomes were employed as nanocarriers for the safe and efficient intracellular delivery of KF into drug-resistant colorectal cancer cells. The KF-loaded exosome (KF-Exo) significantly improved the colloidal stability of KF and enabled sustained drug release. In vitro studies demonstrated that both KF-Exo and free KF increased the levels of p21, a protein linked to cell cycle arrest, in both oxaliplatin (Ox)-resistant HCT116 (HCT116-OxR) and Ox-sensitive HCT116 (HCT116-OxS) cells. Moreover, KF-Exo exhibited higher anticancer activity than free KF in both HCT116-OxR and HCT116-OxS cells. Notably, HCT116-OxR treated with KF-Exo exhibited a higher expression of p21 compared to HCT116-OxS treated with KF-Exo. As a result, KF-Exo exhibited higher inhibition of proliferation in HCT116-OxR cells than in HCT116-OxS cells. This study demonstrates that KF-Exo is an effective chemotherapeutic agent for the safe and efficient treatment of drug-resistant colorectal cancer cells.