Abstract 5528: Development and evaluation of cell membrane lipid-extracted nanoliposomes (CLENs) for the treatment of cancer using cellular models of human pancreatic cancer
Authors: Alqahtani Taha Y. , Campbell Robert 
Published: August 2015

In 2014, an estimated 46,420 people will be diagnosed with pancreatic cancer in the United States, and approximately 39,590 will die from the disease. Gemcitabine has been established as the first-line treatment for advanced pancreatic cancer. However, this type of cancer has responded poorly to many therapeutic agents including gemcitabine, mainly due to inadequate drug accumulation at the desired tumor location and drug resistance. Liposomes represent a convenient method to deliver drugs to solid tumors. The drug carrier enhances the accumulation of the drug at the tumor site and has been shown to overcome drug resistance. Liposomes can direct the drug away from normal tissue and minimize unwanted drug side effects. However, more selective tumor targeting of cytotoxic drug-loaded liposomes to pancreatic tumors will further improve efficacy and will likely reduce toxicity.

The present study investigated whether the inclusion of extracted lipids derived from pancreatic cancer cells would improve the selective uptake of liposomes by pancreatic cancer cells and formulation effects. We hypothesized that the inclusion of cell membrane lipid-extracted materials in the preparation of nanoliposomes will promote selective cellular uptake and improved cytotoxic drug effects. To test the hypothesis, two different pancreatic cancer cell lines were employed for the study (PANC-1 and Capan-2), and hTERT (a human immortalized normal pancreatic duct cell line) used as a healthy cell control. The human prostate (LNCap) and colorectal cancer (COLO-205) cell lines were used as negative controls. Various nanoliposome preparations were prepared and evaluated in terms of particle size, zeta potential and relative affinity of CLENs for target cells and fluorescence microscopy.

The particle size of these nanoliposomes ranged between 92-176 nm and the zeta potential was negatively-charged (-14.07 and -34.95 mV). The Sulforhodamine B cell viability assay showed that CLENs was non-toxic to cells over the full concentration range evaluated when compared to conventional liposomes. The cellular uptake of the five different nanoliposome preparations was highest for the cell line from which the lipid material used to prepare CLENs was extracted (P&lt;0.001). When the same five cell lines were exposed to conventional nanoliposomes the cellular uptake was non-specific by comparison, with no distinction made between all pancreatic cancer cell lines and hTERT (P&gt;0.05). Fluorescence microscopic analyses supported the cellular uptake studies.

The incorporation of gemcitabine in CLENs may represent a promising approach for the treatment of pancreatic cancer. Cytotoxic drug studies with gemcitabine are currently underway.

Citation Format: Taha Y. Alqahtani, Robert Campbell. Development and evaluation of cell membrane lipid-extracted nanoliposomes (CLENs) for the treatment of cancer using cellular models of human pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5528. doi:10.1158/1538-7445.AM2015-5528