한빛사논문
- 조회687
Chaeeun Bang1, Min Gyu Park1, In Kyung Cho1,2, Da‑Eun Lee1, Gye Lim Kim1, Eun Hyang Jang1, Man Kyu Shim1,2, Hong Yeol Yoon2, Sangmin Lee1,3* and Jong‑Ho Kim1,3*
1College of Pharmacy and Bionanocomposite Research Center, Kyung Hee University, Seoul 02447, Republic of Korea.
2Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02797, Republic of Korea.
3Department of Regulatory Science, Graduated School, Kyung Hee University, Seoul 02447, Republic of Korea.
*Correspondence: Sangmin Lee, Jong‑Ho Kim
Abstract
Background: Claudin-4 (CLDN4), a tight junction protein, is overexpressed in several types of cancer, and is considered a biomarker for cancer-targeted treatment. CLDN4 is not exposed in normal cells, but becomes accessible in cancer cells, in which tight junctions are weakened. Notably, surface-exposed CLDN4 has recently been found to act as a receptor for Clostridium perfringens enterotoxin (CPE) and fragment of CPE (CPE17) that binds to the second domain of CLDN4.
Methods: Here, we sought to develop a CPE17-containing liposome that targets pancreatic cancers through binding to exposed CLDN4.
Results: Doxorubicin (Dox)-loaded, CPE17-conjugated liposomes (D@C-LPs) preferentially targeted CLDN4-expressing cell lines, as evidenced by greater uptake and cytotoxicity compared with CLDN4-negative cell lines, whereas uptake and cytotoxicity of Dox-loaded liposomes lacking CPE17 (D@LPs) was similar for both CLDN4-positive and negative cell lines. Notably, D@C-LPs showed greater accumulation in targeted pancreatic tumor tissues compared with normal pancreas tissue; in contrast, Dox-loaded liposomes lacking CPE17 (D@LPs) showed little accumulation in pancreatic tumor tissues. Consistent with this, D@C-LPs showed greater anticancer efficacy compared with other liposome formulations and significantly extended survival.
Conclusions: We expect our findings will aid in the prevention and treatment of pancreatic cancer and provide a framework for identifying cancer-specific strategies that target exposed receptors.
논문정보
- Research article
- 2023년 05월 (BRIC 등록일 2023-06-26)
- 국내 연구진
- 의약학 > 약학
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