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- Title
Liposomes targeting the cancer cell-exposed receptor, claudin-4, for pancreatic cancer chemotherapy.
- Authors
Bang, Chaeeun; Park, Min Gyu; Cho, In Kyung; Lee, Da-Eun; Kim, Gye Lim; Jang, Eun Hyang; Shim, Man Kyu; Yoon, Hong Yeol; Lee, Sangmin; Kim, Jong-Ho
- 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.
- Publication
Biomaterials Research, 2023, Vol 27, Issue 1, p1
- ISSN
2055-7124
- Publication type
Article
- DOI
10.1186/s40824-023-00394-7