Abstract 283: Target cell-derived, G401-CLENs for selective delivery of model therapeutics to rhabdoid tumors

Abstract

One of the rarest and most aggressive pediatric cancers to date is the malignant rhabdoid tumor (MRT), maintaining a survival rate of 16%. Considered a renal cancer, approximately 20-25 new cases are diagnosed in the USA each year, with the average age of diagnosis being about 11 months old. Conventional strategies for treating MRT are limited due to several factors including off-target associated toxicities, patient population, age, metastasis to brain tissue, and diminished survival rates. CLENs (cell membrane lipid-extracted nanoliposomes), a novel drug delivery system, was previously developed and evaluated for selective delivery of cytotoxic drug agents to breast cancer cells and compared to more conventional liposomes. The purpose of this investigation was to optimize and characterize G401-CLENs for selective targeting and delivery of model payloads to a cellular model of rhabdoid tumors. The MRT cell line (G-401 [G401] (ATCC® CRL-1441™) was cultured in McCoy9s 5A Medium (ATCC® 30-2007™), supplemented by 10% FBS. The G401 cellular lipid materials (otherwise known as lipid extracts (LE)) were derived from G401 cells. Follow up studies include the incorporation of G401-LE in liposomes to form G401-CLENs. For development, special consideration was given to distinct determinants of targeting (i.e., particle size and zeta potential) and cellular uptake by G401-CLENs. Other analyses include a comparison of delivery of model and functional siRNA (BRD9 Silencer Select Pre-designed, siRNA ID s35295, Ambion) to G401 target cells using G401-CLENs, and conventional nano-preparations in vitro. G401-LE cell membrane components were extracted from rhabdoid G401 cells. On-going physiochemical characterization studies of G401-CLENs and functional in vitro and fluorescence microscopic analyses are currently underway. Citation Format: Lindsay Bourdeau, Carlos Cruz, Taylor Williams. Target cell-derived, G401-CLENs for selective delivery of model therapeutics to rhabdoid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 283.