Abstract 1322: Evaluating intracellular accumulation profiles of chemotherapeutic agents using CLENs for the treatment of Y79 retinoblastoma

Abstract

Abstract Retinoblastoma is the most common intraocular malignancy in children, with approximately 200-300 new cases in the United States each year. Currently, conventional chemotherapy agents (carboplatin, cisplatin, doxorubicin, vincristine, and cyclophosphamide) used to treat retinoblastoma, are rapidly eliminated from circulation. Novel lipid nanoparticles (LNP) have been shown to improve delivery of encapsulated chemotherapeutic agents to Y79 retinoblastoma cells, and therefore the agents are less toxic to healthy cells. Past studies have supported the use of LNP delivery systems to enhance chemotherapeutic drug action against Y79 retinoblastoma cells as well. The experimental plan will now evaluate the use of cellular membrane lipid-extracted nanoliposomes (CLENs) to examine targeting using cellular models of retinoblastoma. Y79 cells were cultured in RPMI growth medium supplemented by 20% FBS. CLENs and lipid extracts (LE) were prepared according to previously published protocols. Following the development of Y79-LE nano-preparations consisting of DOPC, Y79-LE, and cholesterol at different ratios, preparations were evaluated in terms of physicochemical properties and uptake by Y79 cells. The additional inclusion of cationic lipid DOTAP in Y79-LE preparations was evaluated for select preparations. Particle sizes and zeta potential values were determined for each preparation type by ZetaPALS. CLENs exhibited an average particle size between 400 to 600 nm. Experiments with Y79-CLENs prepared in the absence and presence of DOTAP, showed they were taken up by the target cell population. In general, the inclusion of Y79-LE increased cellular uptake. The inclusion of cholesterol in combination with DOTAP showed enhanced liposomal uptake in Y79 retinoblastoma cells. Evidence from previous studies suggest a benefit of using lipid nanoparticles compared to more conventional treatment options. Preliminary findings suggest a positive correlation between the particle size and degree of cellular uptake. Additional optimization studies are currently underway. Citation Format: Nan Luo, Virali Patel, Minesh Patel, Eric Conte, Robert Campbell. Evaluating intracellular accumulation profiles of chemotherapeutic agents using CLENs for the treatment of Y79 retinoblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1322.