Abstract
Abstract Background: Every year more deaths are attributed to lung cancer compared to colon, prostate, and breast cancers combined. Lung cancer is typically diagnosed at late stages, and has demonstrated poor treatment outcomes due to acquired drug resistance. Unfortunately, as one method is introduced to overcome drug resistance a new mechanism can arise. In an effort to overcome drug resistance lipid extracts (LE) were derived from target cells, and the ingredients were used to develop nanoliposomes that would selectively target a desired cell population compared to controls. The early studies were designed to demonstrate the use of CLENs (cellular membrane lipid-extracted nanoliposomes) for the targeting of lung cancer. Experimental Procedures: CLENs were initially prepared using various ratios of LE/DOPC/Chol/PEG by thin film evaporation. Particle size and zeta potential values were determined for all preparations of CLENs (with and without drug). CLENs were evaluated for selectivity for target compared to control cells. Cytotoxicity studies were performed on various doxorubicin hydrochloride-loaded CLENs using a cell model of lung cancer (ChagGo-K-1). For cellular uptake studies ChaGo-K-1 cells were seeded at 10,000 cells/mL in a 48-well plate and allowed to incubate for 24 hours prior to cell studies. A fluorescence microplate reader was used to determine fluorescence intensity values for the two studies. Results: ChaGo-K-1 CLENs demonstrated an average particle size of 206+/-2 nm and zeta-potential of -21+/-3 mV, illustrating favorable characteristics for drug delivery and interstitial drug targeting. The cellular uptake studies suggested that ChaGo-K-1 CLENs were selective for ChaGo-K-1 cells in vitro, when compared to all other control varieties of CLENs. Drug-loaded ChaGo-K-1 CLENs displayed significant cytotoxicity against ChaGo-K-1 cells compared to control cells. Fluorescence microscopy revealed association of ChagGo-K-1 CLENs with target cells. Conclusions: Based on promising early finding CLENs may represent a relatively tumor specific drug delivery system that can be used to overcome drug resistance, improve efficacy, and to limit off-target drug effects. Preclinical studies will investigate whether the relative selectivity and cytotoxicity observed against lung cancer cells in vitro translates to favorable tumor uptake and efficacy in vivo. Citation Format: Jasmine King, Aarohi Bhatt, Drew Goodrich, Thomas Preteroti, Hanan Alharbi, Robert Campbell. Development and in vitro evaluation of cell membrane lipid-extracted nanoliposomes for lung cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3876.
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