Abstract A120: The effect of targeted nanoemulsion on pancreatic cancer cells

Abstract

Abstract Purpose: Pancreatic cancer is characterized by its extreme aggressiveness and limited treatment options. This work evaluates the targeting of a nanoemulsion containing doxorubicin (DOX) to different pancreatic cancer cell lines and its mechanism of uptake. Methods: Three human pancreatic cancer cell lines, PANC-1, BxPC-3, and MIA PACA-2, were seeded separately into 12-well plates (1.0 x 105 cells/well). Then the cells were treated with DOX alone or DOX in targeted or nontargeted nanoemulsions. Cells treated with culture medium only were used as negative controls. The cellular uptake of the different DOX formulations by the different pancreatic cancer cell lines was evaluated using a fluorescence microscope (EVOS) and a flow cytometer (Accuri). The cytotoxicity of different formulations was evaluated using the SRB assay. The uptake mechanism of the DOX in targeted and nontargeted nanoemulsions was evaluated by comparing the uptake when cells were incubated at 40C and 370C. The uptake mechanism was further evaluated by pretreatment of the cells with inhibitors: cytochalasin D (inhibits caveolin-mediated endocytosis), chlorpromazine (inhibits clathrin mediated endocytosis), amiloride (inhibits micropinocytosis), and nystatin (depletes cholesterol and affects rafts). Results: The uptake of DOX in targeted nanoemulsion by PANC-1, BxPC-3, and MIA PACA-2 cell lines was 1.4-fold, 1.2-fold, and 1.2-fold higher, respectively, compared to that of DOX in the nontargeted nanoemulsion. The IC50 value for DOX in targeted nanoemulsion was 0.3 uM, for DOX in nontargeted nanoemulsion was 0.6 uM, and for DOX only was 1.3 uM. The uptake of DOX in targeted nanoemulsion and nontargeted nanoemulsion was higher at 370C compared to that at 40C. None of the inhibitors used had a significant effect on the uptake of DOX in the targeted or nontargeted nanoemulsions. Conclusion: The results show that DOX in the targeted nanoemulsion has significantly higher cellular uptake and cytotoxicity compared to that of the nontargeted nanoemulsion. The uptake of DOX in targeted and nontargeted nanoemulsion is energy dependent. However, none of the inhibitors used has a significant effect on the uptake of DOX in the targeted nanoemulsion, which requires further studies. Citation Format: QinQin Fei, Sophia O'Barr, Maria P. Lambros. The effect of targeted nanoemulsion on pancreatic cancer cells [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A120.