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Original Article

Korean J Physiol Pharmacol 2023; 27(1): 31-38

Published online January 1, 2023 https://doi.org/10.4196/kjpp.2023.27.1.31

Copyright © Korean J Physiol Pharmacol.

Characterization of a conjugated polysuccinimide-carboplatin compound

Sun Young Lee1,2, Chang Hoon Chae3, Miklós Zrínyi4, Xiangguo Che5, Je Yong Choi5, and Dong-Hyu Cho2,6,*

1Department of Radiation Oncology, Jeonbuk National University Medical School, Jeonju 54907, 2Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, 3CELLDI Co., Ltd, Cheongju 28160, Korea, 4Laboratory of Nanochemistry, Department of Biophysics and Radiation Biology, Semmelweis University, Budapest 1089, Hungary, 5Department of Biochemistry & Cell Biology, School of Medicine, Kyungpook National University, Daegu 41940, 6Department of Obstetrics and Gynecology, Jeonbuk National University Medical School, Jeonju 54907, Korea

Correspondence to:Dong-Hyu Cho
E-mail: obgyn2001@jbnu.ac.kr

Author contributions: Conceptualization: S.Y.L., C.H.C., M.Z., X.C, J.Y.C., and D.H.C. Data curation: S.Y.L., C.H.C., M.Z., X.C., J.Y.C., and D.H.C. Writing – original draft preparation: S.Y.L., C.H.C., M.Z., and X.C. Writing – review and editing: S.Y.L., C.H.C., M.Z., X.C., J.Y.C., and D.H.C. Visualization: S.Y.L., C.H.C., M.Z., and X.C. Validation: D.H.C. Supervision: M.Z., X.C., J.Y.C, and D.H.C. All authors approved the version of the manuscript to be published and agree to be accountable for all aspects of the work.

Received: May 18, 2022; Revised: November 8, 2022; Accepted: November 14, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Carboplatin, an advanced anticancer drug with excellent efficacy against ovarian cancer, was developed to alleviate the side effects that often occur with cisplatin and other platinum-based compounds. Our study reports the in vitro characteristics, viability, and activity of cells expressing the inducible nitric oxide synthase (iNOS) gene after carboplatin was conjugated with polysuccinimide (PSI) and administered in combination with other widely used anticancer drugs. PSI, which has promising properties as a drug delivery material, could provide a platform for prolonging carboplatin release, regulating its dosage, and improving its side effects. The iNOS gene has been shown to play an important role in both cancer cell survival and inhibition. Herein, we synthesized a PSI-carboplatin conjugate to create a modified anticancer agent and confirmed its successful conjugation. To ensure its solubility in water, we further modified the structure of the PSI-carboplatin conjugate with 2-aminoethanol groups. To validate its biological characteristics, the ovarian cancer cell line SKOV-3 and normal ovarian Chinese hamster ovary cells were treated with the PSI-carboplatin conjugate alone and in combination with paclitaxel and topotecan, both of which are used in conventional chemotherapy. Notably, PSI-carboplatin conjugation can be used to predict changes in the genes involved in cancer growth and inhibition. In conclusion, combination treatment with the newly synthesized polymer-carboplatin conjugate and paclitaxel displayed anticancer activity against ovarian cancer cells but was not toxic to normal ovarian cancer cells, resulting in the development of an effective candidate anticancer drug without severe side effects.

Keywords: Carboplatin, Conjugation, iNOS, Ovarian cancer, Polysuccinimide