The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Characterization of a conjugated polysuccinimide-carboplatin compound

  • Sun Young Lee (Department of Radiation Oncology, Jeonbuk National University Medical School) ;
  • Chang Hoon Chae (CELLDI Co., Ltd) ;
  • Miklos Zrinyi (Laboratory of Nanochemistry, Department of Biophysics and Radiation Biology, Semmelweis University) ;
  • Xiangguo Che (Department of Biochemistry & Cell Biology, School of Medicine, Kyungpook National University) ;
  • Je Yong Choi (Department of Biochemistry & Cell Biology, School of Medicine, Kyungpook National University) ;
  • Dong-Hyu Cho (Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital)
  • Received : 2022.05.18
  • Accepted : 2022.11.14
  • Published : 2023.01.01
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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

Acknowledgement

This paper was supported by the Fund of the Biomedical Research Institute, Jeonbuk National University Hospital, the Research Base Construction Fund Support Program funded by Jeonbuk National University in 2021, and research funds for newly appointed professors of Jeonbuk National University in 2020.

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