Anti-Tumor Efficacy of Oleuropein-Loaded ZnO/Au Mesoporous Silica Nanoparticle in 5-FU-Resistant Colorectal Cancer Cells

Sang Mi Park,1,2 Da Yeon Kim,3 Kyeong Hyeon Lee,1 Yong-Il Shin,1,4 Sang-Cheol Han,5 Sang-Mo Kwon1,2 1Department of Physiology, Laboratory of Vascular Medicine and Stem Cell Biology, School of Medicine, Pusan National University, Yangsan, Republic of Korea; 2BK21 GRAND Convergence Medical Science Education Research Center, Pusan National University, Yangsan, South Korea; 3Genetic & Epigenetic Toxicology Research Group, Korea Institute of Toxicology (KIT), Daejeon, Republic of Korea; 4Department of Rehabilitation Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea; 5CEN Co., Ltd. Nanoconvergence Center, Muan-ro, Miryang, 761, Republic of KoreaCorrespondence: Sang-Mo Kwon, Department of Physiology, Laboratory of Vascular Medicine and Stem Cell Biology, School of Medicine, Pusan National University, Yangsan, Republic of Korea, Tel +82-51-510-8072, Fax +82-51-510-8076, Email smkwon323@pusan.ac.krPurpose: 5-fluorouracil (5-FU) is a first-line chemotherapeutic agent used to treat colorectal cancer (CRC). However, 5-FU induces drug resistance and activation of cancer stem cells (CSCs). In the present study, we designed a novel biocompatible nanomedicine system with high efficacy and biocompatibility by synthesizing mesoporous silica nanoparticle (MSN)-structured ZnO and gold ions. Oleuropein (OLP) is a phenolic compound derived from olive leaves that exerts anti-cancer effects. Therefore, we synthesized OLP-loaded ZnO/Au MSNs (ZnO/Au/OLP MSNs) and examined their anti-cancer effects on 5-FU-resistant CRC cells.Methods: ZnO/Au MSNs were synthesized and functionalized, and their physical and chemical compositions were characterized using UV-visible spectroscopy, dynamic light scattering, and transmission electron microscopy (TEM). Their effects were assessed in terms of cellular proliferation capacity, migration and invasion ability, colony-forming ability, spheroid-forming ability, reactive oxygen species (ROS) production, and mitochondrial me