Abstract 4047: Targeted liposomes against ovarian cancer

Abstract

Abstract Purpose: Cisplatin (CPT) is a first-line chemotherapeutic agent for the treatment of ovarian cancer. However, CPT has severe adverse effects. The purpose of this study is to develop targeted liposomes that selectively target the xCT transporter which is upregulated in ovarian cancer and carry CPT to ovarian cancer only, thereby avoiding the adverse effects of CPT. We evaluated the stability, the cytotoxicity and the cellular uptake of targeted liposomes in ovarian cancer cell lines. Methods: CPT was encapsulated by the remote loading method in liposomes. The stability of liposomes was evaluated by measuring the drug-leakage from liposomes and the growth of liposome size stored at 4°C and room temperature over a 30-day period. For the drug-leakage study, liposomes were placed into a dialysis tubing and dialysate aliquots were removed and analyzed twice weekly for CPT content. The liposome size was evaluated using Dynamic Light Scattering (Nano Brook Omni, Brookhaven Instruments). The cellular uptake of targeted liposomes (encapsulating the fluorescent dye sulforhodamine B, SRB) was evaluated in drug-resistant (A2870cis, OVCAR3, OVCAR4, IGROV1, and NCI/ADR-RES) and drug sensitive (A2870 and OVCAR8) ovarian cancer cell lines (purchased from the NIH), were evaluated using flow cytometry (BD Accuri C6). The cytotoxicity of CPT in targeted liposomes was evaluated in the various ovarian cell lines using the MTS assay (Novus Biologicals). Results: The targeted liposomes over the 30-day period, show that 6.8% of the total loaded CPT leaked out of the liposomes. During that period the growth of the liposomes was <5% for the liposomes stored at 4°C and <1% of their initial size, stored at 25°C. The cellular uptake of ovarian cancer cell lines, A2870, A2870cis, OVCAR3, OVCAR4, OVCAR8, and NCI/ADR-Res the targeted SRB loaded liposomes showed significantly more fluorescence intensity when compared to free SRB and non-targeted liposomes (p<0.05). In the cell line IGROV1, there is a similar trend seen, where there was a higher fluorescence intensity compared to free SRB and non-targeted. The fluorescence intensity was found to be higher compared to non-targeted liposomes (p<0.0001) but not statistically significant higher compared to free SRB. For cytotoxicity, a similar trend is seen in cell lines A2870, A2870cis, IGROV1, OVCAR3, OVCAR4, OVCAR8, and NCI/ADR-res, where the cisplatin loaded targeted liposomes had the lowest IC50 compared to free drug and non-targeted liposomes. Non-targeted liposomes had the highest IC50 values compared to free drug and targeted liposomes. In cell lines A2870, A2870cis, IGROV1, OVCAR3, OVCAR4, OVCAR8, and NCI/ADR-res the IC50 values show a 2.4, 5.3, 4.1, 3.3, 1.7, 1.6, and 2.5-fold lower values compared to free cisplatin, respectively. Conclusion: Targeted liposomes encapsulating CPT show stability, enhanced in-vitro cellular uptake and anti-cancer activity in resistant and sensitive ovarian cancer cell lines. Citation Format: Antonia Marashio, Maria (Mary) P. Lambros, Adenike Oyegbesan. Targeted liposomes against ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4047.