Biotechnology and Bioprocess Engineering 2024; 29(6): 1108-1117  
Safe and efficient treatment of drug-resistant colorectal cancer cells using kaempferol-loaded exosomes
Jun Min 1 · Dohyun Jeung 2 · Dae Gyun Lee 1 · Hyeon Ju Kang 1 · Ha Young Jo 1 · Le Thi Hong Tram 1 · Han Chang Kang 2 · Joo Young Lee 2 · Hye Suk Lee 2 · Won Jong Rhee 1 · Byoung Choul Kim 1 · Yong-Yeon Cho 2 · Min Suk Shim 1
1 Department of Bioengineering and Nano-Bioengineering, Incheon National University, Incheon 22012, Korea
2 BRL & BK-4Th Team, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea
Correspondence to: ✉ Yong-Yeon Cho
yongyeon@catholic.ac.kr

✉ Min Suk Shim
msshim@inu.ac.kr

Jun Min and Dohyun Jeung have contributed equally to this work.
Received: June 5, 2024; Revised: October 14, 2024; Accepted: October 23, 2024; Published online: November 14, 2024.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
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.
Keywords: Exosome · Drug resistance · Colorectal cancer · Kaempferol · p21

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