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 2024-01-19T09:32:56Z 2024-01-19T09:32:56Z 2023-06-08 2023-05 1226-4601 https://pubs.kist.re.kr/handle/201004/113753 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. English The Korean Society for Biomaterials | BioMed Central Liposomes targeting the cancer cell-exposed receptor, claudin-4, for pancreatic cancer chemotherapy Article 10.1186/s40824-023-00394-7 1 Biomaterials Research, v.27, no.1, pp.1434 - 1445 Biomaterials Research 27 1 1434 1445 Y scie scopus kci ART003005646 000995939000001 2-s2.0-85160263905 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article IN-VIVO NANOPARTICLES EXPRESSION DELIVERY