Abstract 237: Evaluation of cell membrane lipid-extracted nanoliposomes (CLENs) as a potential drug platform for targeting multiple myeloma

Abstract

Abstract Background: Multiple myeloma (MM) is a plasma cell malignancy that primarily affects the elderly. MM is the second most common hematologic cancer with approximately 25,000-30,000 new cases diagnosed annually in the United States. A challenge associated with MM therapy is unwanted drug uptake by normal healthy cells. Nanoparticles provide a promising outlook to mitigate these issues, offering more selective drug uptake, while minimizing toxicity associated with treatment. The objective of this study was to develop, optimize and evaluate physicochemical and In vitro properties of MM-CLENs in comparison to conventional liposomes and relevant cell controls. Methods: RPMI-8226 MM cell line was selected cellular model for MM disease. RPMI-8226 cells were cultured and expanded In vitro for cellular extraction purposes. Lipid extraction (LE) procedures were performed to generate the RPMI-8226 LE ingredient. Other lipid ingredients used in preparation of RPMI-8226 CLENs included DOPC, cholesterol, and DPPE-Rhodamine (fluorescence indicator). Phase I included physicochemical characterization and cellular uptake studies of CLENs preparations with varying concentration of RPMI-8226-LE (0 to 40 mol%) content. Phase II began with the optimized concentration of LE determined in Phase I, along with varying concentrations of cholesterol (0 to 40 mol %) content for the nano-targeting studies in vitro. The control cell lines represent other hematological diseases, K-562-GFP (chronic myeloid leukemia), CCRF-CEM (acute lymphoblastic leukemia), and U937 (lymphoma). Results: Phase I and II physicochemical characterization and In vitro studies, revealed that the optimized preparation of RPMI-8226-CLENs consisted of 5% LE, and 5% cholesterol content. Optimal preparation consisted of DOPC: Cholesterol: LE (90:5:5) with an average values for particle size and zeta potential of 178±38 nm (n=4), and -14±4 mV (n=4), respectively. The inclusion of LE in conventional DOPC:cholesterol liposomes resulted in significantly improved uptake of the CLENs by RPMI-8226 cells in vitro (P< 0.001). However, preliminary selectivity studies suggest no significant difference in the uptake of RPMI-8226-CLENs by RPMI-8226 when compared to control cells (K-562-GFP, CCRF-CEM and U937). Conclusion: Studies involving RPMI-8226 CLENs are currently underway. Such studies include target selectivity, and influence of additional components of CLENs as a function of the microenvironment. Citation Format: Christina T. Tran, Eden Park, Pedro L. Rodriguez-Flores, Robert B. Campbell. Evaluation of cell membrane lipid-extracted nanoliposomes (CLENs) as a potential drug platform for targeting multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 237.