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Han Yu,1– 4 Na Ning,1– 3 Fujin He,5 Jiao Xu,6 Han Zhao,5 Shaofeng Duan,5,7 Yunqi Zhao1– 4 1College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou, Zhejiang Province, 325060, People’s Republic of China; 2Wenzhou Municipal Key Laboratory for Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou, Zhejiang, 325060, People’s Republic of China; 3Zhejiang Bioinformatics International Science and Technology Cooperation Center, Wenzhou-Kean University, Wenzhou, Zhejiang, 325060, People’s Republic of China; 4Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, Union, NJ, 07083, USA; 5School of Pharmacy, Henan University, Kaifeng, Henan, 475004, People’s Republic of China; 6Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325001, People’s Republic of China; 7The First Affiliated Hospital of Henan University, Kaifeng, Henan, 475004, People’s Republic of ChinaCorrespondence: Yunqi Zhao, College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou, Zhejiang, 325060, People’s Republic of China, Tel +86 577 5587 0000, Fax +86 577 5587 0101, Email yuzhao@kean.edu Shaofeng Duan, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, People’s Republic of China, Fax +86 371 2286 5974, Email sduan@henu.edu.cnBackground: Targeted delivery systems have been developed to improve cancer treatment by reducing side effects and enhancing drug efficacy. Geraniol, a natural product, has demonstrated promising anti-cancer effects in various cancer types, including prostate cancer, which is the most commonly diagnosed cancer in men. Hyaluronic acid (HA), a natural carrier targeting CD44-positive prostate cancer cells, can be utilized in a targeted delivery system.Purpose: This study investigated the efficacy of a conjugate of HA and geraniol linked via a disulfide bond linker (HA-SS-Geraniol) in prostate cancer.Materials and Methods: The cytotoxicity of HA-SS-Geraniol was evaluated on human PC-3 prostate cancer cells. Flow cytometry was used to assess its effects on mitochondrial membrane potential, apoptosis, and cell cycle arrest. Additionally, proteomic analysis was conducted to explore the underlying mechanism of action induced by HA-SS-Geraniol treatment. A subcutaneous xenograft tumor model was established in nude mice to evaluate the toxicity and efficacy of HA-SS-Geraniol in vivo.Results: The results demonstrated that HA-SS-Geraniol exhibited potent cytotoxicity against PC-3 prostate cancer cells by inducing mitochondrial membrane potential loss and apoptosis in vitro. The proteomic analysis further supported the hypothesis that HA-SS-Geraniol induces cell death through mitochondria-mediated apoptosis, as evidenced by differential protein expression. The in vivo mouse model confirmed the safety of HA-SS-Geraniol and its ability to inhibit tumor growth.Conclusion: HA-SS-Geraniol holds promise as a biologically safe and potentially effective therapeutic agent for prostate cancer treatment. Its targeted delivery system utilizing HA as a carrier shows potential for improving the efficacy of geraniol in cancer therapy.Keywords: geraniol, hyaluronic acid, prostate cancer, nanoparticle, proteomics |
