Abstract 5074: Investigating the cellular uptake of liposomal delivery system using cellular models of lymphoma

Abstract

Abstract Background: Lymphoma accounts for more than 4% of cancer diagnoses in the United States. Conventional treatment strategies for lymphoma are effective, but face a multitude of challenges limiting efficacy. Nanomedicine presents a viable option to optimize the efficacy of current anti-lymphoma therapies. To achieve most selective drug targeting, optimization of liposome preparations is key. To improve the selective targeting properties of conventional liposomes, cell membrane lipid-extracted nanoliposomes (CLENs) were prepared using lipids extracted from lymphoma target cells. Reported here is results of initial design and development, including physicochemical characterization and in vitro analyses. Methods: The CRL-1593.2 cell line was the chosen cellular model of lymphoma. CRL-1593.2 cells were cultured and expanded In vitro for cellular extraction purposes. The CRL-1593.2 cell lipid extract (LE) was included to prepare CRL-1593.2 CLENs. Conventional lipid ingredients used in preparation of CRL-1593.2-CLENs included DOPC, Cholesterol, and DPPE-Rhodamine (used as a fluorescence indicator) for fluorescence studies using a fluorescence microplate reader. Phase I studies included physicochemical characterization and cellular uptake studies of preparations of CLENs, including 0 to 40 mol% of CRL-1593.2 LE content. In Phase II, the optimal LE content as determined by Phase I was fixed, while cholesterol content varied from 0 to 40 mol%.. For in vitro studies, the control cell lines employed represented other hematological diseases, RPMI 8226 (multiple myeloma), CCRF-CEM (acute lymphoblastic leukemia), and K562-GFP (chronic myeloid leukemia). Results: The optimized composition of CLEN preparation type consisted of DOPC: Cholesterol, lymphoma lipid extract (derived from CRL-1593.2 cells) in the ratio of 93:5:2. The mean particle size was 116 ± 10 nm (n=4) and the mean zeta potential was - 4.5 ± 5 mV (n= 4). For in vitro studies, the inclusion of 2 mol% LE in CRL-1593.2-CLENS demonstrated significant uptake when compared to 0% LE control preparations (P = 0.016). Additionally, the lymphoma cells also had a significantly higher uptake of the CRL-1593.2-CLENs when compared to the other hematological cell lines [(CCL-155; P = 0.0081), (K562-GFP; P = 0.0037) and, (CCRF-CEM; P = 0.0079)]. Conclusions: Early findings collectively suggest that the CRL-1593.2-CLENs is a highly selective drug delivery platform for the targeting of lymphoma cells. Citation Format: Joyce Edlyne Chima Bom, Tien Van Le, Tracy Togba-Bass, Erica Kim, Robert Campbell. Investigating the cellular uptake of liposomal delivery system using cellular models of lymphoma [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 5074.