Abstract 3196: Overcoming lung cancer drug resistance: Enhanced cellular delivery using lipid-extracted nanoliposomes

Abstract Background: Lung cancer causes substantial cancer deaths in the U.S. Drug resistance remains a major issue. Nanoliposomes demonstrate enhanced drug targeting and resistance-overcoming potential. Incorporating lipid extracts derived from target cells shows improved delivery over conventional nanoliposomes. This study examined the effects of lung cancer cell lipid extract nanoliposomes against target and non-target cell populations from different environments. Method: Cellular Membrane Lipid-Extracted Nanoliposomes (CLENs) were fabricated with DOPC, DOTAP, ChaGo-K-1 lipid extract, cholesterol, PEG5000, and rhodamine fluorescent label was incorporated for uptake studies. The liposome size was reduced by probe sonication. Particle size and polydispersity index (PDI) were measured by dynamic light scattering. Zeta potential was quantified by laser Doppler micro-electrophoresis. Four cell lines were utilized: ChaGo-K-1 NSCLC target, A549 pulmonary microenvironment control, 4T1 extra-pulmonary control, and normal lung fibroblasts off-target control. All cell lines were cultured in 48-well plates at a seeding density of 10,000 cells/mL and incubated for 24 hours. Freshly prepared CLENs were added to all cell lines and incubated for an additional 24 hours. Cells were washed with PBS, and fluorescence intensity was then quantified and qualified by a microplate reader to measure the cellular uptake of the CLENs. Results: The mean particle size and PDI of the ChaGo-K-1 CLENs were 117 ± 0.7 nm and 0.216 ±0.009, compared to 126 ± 0.5 nm and 0.195 ± 0.008 for the control, respectively. Both formulations were within the optimal size range for drug delivery and tumor cell penetration. The zeta potential of the ChaGo-K-1 CLENs was -1.75 ± 1.81 mV compared to -1.74 ± 6 mV for the control. Quantification and qualification of cellular uptake using fluorescence intensity measurements revealed a 3.2-fold increase in ChaGo-K-1 CLENs compared to conventional liposomes without ChaGo-K-1 lipid extracts. This demonstrates that the inclusion of the lipid extracts in the CLEN significantly enhanced selectivity and delivery to target cancer cell populations. Conclusion: Higher uptake occurred with target cells using CLENs with lipid extracts versus standard liposomes. NSCLC-derived CLENs show potential to improve selective delivery and overcome drug resistance. Further, in vivo studies evaluating selective NSCLC tumor accumulation and efficacy enhancement are warranted. Citation Format: Mohammed Alqaryan, Rashad Allahyani, Dayeoun Lee, Robert B. Campbell. Overcoming lung cancer drug resistance: Enhanced cellular delivery using lipid-extracted nanoliposomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3196.