Abstract 831: Selective targeting of pediatric rhabdoid tumor using G401-CLENs: Cytotoxicity studies

Abstract

Abstract Background: Rhabdoid tumor is an aggressive soft tissue sarcoma that arises in the kidney, liver, peripheral nerves, and miscellaneous soft parts throughout the body. Rhabdoid tumors usually occur in infancy or during early childhood and the most common sites for metastasis are lungs, abdominal lymph nodes, liver, and brain. Current treatment options include surgery, radiation therapy, high-dose chemotherapy, and stem cell transplant but the overall survival rate is approximately 23%. Nano-sized liposomes are drug-delivery vehicles used to enhance the delivery of drugs to target cells. The composition, size, and overall charge of nanoliposomes determine targeting and influence the degree of drug uptake. The objective of this study was to develop G401-CLENs prepared from lipid extracts derived from rhabdoid tumor cells and conventional lipid components, and to evaluate the optimized drug loaded preparations of rhabdoid-CLENs in vitro. Methods: Rhabdoid tumor cell line, G401, was the chosen model for this study. G401 cells were cultured and expanded in vitro for cellular extraction purposes. The G401 cell membrane lipid extract (LE) was included in the preparation of G401-CLENs. Additional conventional lipid ingredients include DOPC, DOTAP, and DPPE-PEG5000. DPPE-rhodamine lipids were employed for fluorescence studies only. Chemo agents' doxorubicin and vinblastine were used in cell viability and cytotoxicity assays to evaluate formulation efficacy. Phase I of evaluation included physiochemical characterization and cellular uptake studies of preparations of CLENs, including 0 to 20 mol% of G401 LE content. Phase II of evaluation included the use of Hoechst33342/propidium iodide cell viability and cytotoxicity assays with varied amounts of doxorubicin and vinblastine loaded CLENs added to the G401 cells. The control cell line used in the study represents another solid tumor, SK-N-DZ (neuroblastoma). Results: The optimal composition for G401-CLENs was DOPC/DPPE-PEG5000/LE (93/2/5). The average size and zeta potential was 198 ± 16 nm (n=5) and -12 ± 1.2 mV (n=5), respectively. Cell selectivity studies revealed an increase in the uptake of the optimized G401-CLENs by G401 cells when compared to SK-N-DZ control cells. In general, the inclusion of DOTAP increased overall cellular uptake, but diminished selective uptake of G401-CLENs. Results support a significant cellular uptake of preparations consisting of 5 mol% LE compared to 0, 10, and 20 mol% G401 LE content. Doxorubicin loaded in G401-CLENs decreased rhabdoid tumor cell viability in a dose-dependent manner compared to doxorubicin loaded in conventional liposome preparations. Additional cytotoxicity studies are currently underway. Conclusion: To this date, G401-CLENs represents a promising selective drug-targeting vehicle for the treatment of rhabdoid tumors. Citation Format: Varun Kudchadker, Dongxiao Chen, Yeji Seo, Robert Campbell. Selective targeting of pediatric rhabdoid tumor using G401-CLENs: Cytotoxicity studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 831.