Related Experiment Video
Updated: Jul 29, 2025
Uptake of New Lipid-coated Nanoparticles Containing Falcarindiol by Human Mesenchymal Stem Cells
Published on: February 9, 2019
Liposomes targeting the cancer cell-exposed receptor, claudin-4, for pancreatic cancer chemotherapy
Chaeeun Bang1, Min Gyu Park1, In Kyung Cho1,2
1College of Pharmacy and Bionanocomposite Research Center, Kyung Hee University, Seoul, 02447, Republic of Korea.
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.
Insights
Researchers developed doxorubicin-loaded, CPE17-conjugated liposomes (D@C-LPs) that target Claudin-4 (CLDN4)-expressing pancreatic cancers. D@C-LPs demonstrated enhanced tumor accumulation, cytotoxicity, and improved survival in preclinical models.
Area of Science:
- Biochemistry
- Oncology
- Nanotechnology
Background:
- Claudin-4 (CLDN4) is a tight junction protein overexpressed in cancers, serving as a biomarker for targeted therapies.
- Surface-exposed CLDN4 in cancer cells acts as a receptor for Clostridium perfringens enterotoxin (CPE) fragments like CPE17.
Purpose of the Study:
- To develop a novel liposome formulation utilizing CPE17 to target pancreatic cancers by binding to exposed CLDN4.
- To evaluate the efficacy of CPE17-conjugated liposomes in preclinical models of pancreatic cancer.
Main Methods:
- Conjugation of CPE17 to doxorubicin-loaded liposomes (D@C-LPs) for targeted delivery.
- In vitro assessment of liposome uptake and cytotoxicity in CLDN4-positive and negative cell lines.
- In vivo evaluation of tumor accumulation, anticancer efficacy, and survival in pancreatic cancer models.
Main Results:
- D@C-LPs showed preferential uptake and enhanced cytotoxicity in CLDN4-expressing cancer cells compared to CLDN4-negative cells.
- D@C-LPs exhibited greater accumulation in pancreatic tumor tissues than non-targeted liposomes (D@LPs).
- D@C-LPs demonstrated superior anticancer efficacy and significantly extended survival in preclinical models.
Conclusions:
- CPE17-conjugated liposomes represent a promising strategy for targeted pancreatic cancer therapy.
- The findings provide a framework for developing cancer-specific treatments targeting exposed receptors like CLDN4.
