Abstract 246: Glioblastoma cell-modified cell membrane lipid-extracted nanoparticles (CLENs) for imaging and treatment: Influence of magnetic nanoparticle on physiochemical properties of CLENs, cellular uptake, and cytotoxicity

Abstract

Abstract Background: Glioblastoma multiforme (GBM), located in the cerebral hemispheres of the brain, is the most aggressive form of cancer. Surgery associated with chemotherapy with radiation treatment is the defined way to treat the disease. The delivery of chemotherapeutic agents frequently result in serious side effects. To address this issue we have taken the first steps in the development of CLENs (cell membrane lipid-extracted nanoliposomes) to enhance selective delivery of drugs to the brain. Method: The CLENs used for the experiments were composed of various ratios of DOPC, DOTAP, cholesterol, and lipid extract (LE) material derived from the target cells (i.e., U87-MG), and DPPE-PEG5000 (PEG). Studies include the determination of drug (cisplatin) loading, magnetite (MAG-C) loading in CLENs, quantitative studies for particle size, zeta potential, SQUID (superconducting quantum interference device) measurements, and fluorescence detection to study cellular interactions. Results: The average size for the CLENs fell within the range of 130 to 190 nm. The zeta potential reported for CLENs was negatively-charged. The inclusion of 15mol % LE resulted in the most significant cellular uptake by target cell U87-MG. Overall, the uptake by these cells was less compared to CLENS previously published for other organ tissue environments such as with breast tissue. The inclusion of cationic lipid DOTAP in CLENs did not alter the size distribution; however, the values for zeta potential increased from -8 ± 5 to 12 ± 6 mv. The additional inclusion of DOTAP in CLENs increased cellular uptake approximately 4-fold compared to CLENs without DOTAP (fluorescence intensity (A.U) from 145 ± 52 to 525 ± 49)). The inclusion of DOTAP increased the efficiency of loading Cisplatin in CLENs by approximately 30%. Studies involving the incorporation of MAG-C in U87-MG CLENs are currently underway, as well magnetization studies involving SQUID. Conclusion: All CLENs demonstrated practical physicochemical properties similar to conventional liposomes. The cellular uptake results suggested that cellular uptake of CLENs in vitro, although relatively low overall, varied according to the total LE content. Furthermore, the inclusion of DOTAP in CLENs significantly increased uptake and the efficiency of drug loading. Citation Format: Woongjae Song, Robert Campbell. Glioblastoma cell-modified cell membrane lipid-extracted nanoparticles (CLENs) for imaging and treatment: Influence of magnetic nanoparticle on physiochemical properties of CLENs, cellular uptake, and cytotoxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 246.