Evaluation of Lipoprotein Mimetic Anthracycline Formulation for the Treatment of Ewing Sarcoma

Abstract

Purpose: Anthracyclines are effective in treating many types of cancer, including pediatric cancers such as Ewing Sarcoma. Currently, their use is limited due to cardiotoxicity, but a novel drug delivery method using lipoprotein-based technologies could mitigate this via selective delivery of its payload to cancer cells using a receptor-mediated mechanism. Methods: A soluble formulation of HDL-mimetic peptide (Myr-5A)-Valrubicin was fabricated using Nanoassemblr. Payload efficiency was characterized using spectrophotometric measurements. Size and zeta potential were measured with Zetasizer. Homogeneity was measured using FPLC. Hemolysis assays were performed by incubating Rabbit Red Blood Cells with Myr-5A-Valrubicin at different time intervals and measuring the absorbance of the supernatant at 550nm after centrifugation for 5 minutes. Cytotoxicity assays were performed on Ewing sarcoma cell lines TC205, TC32, CHLA10 and rat cardiomyocytes H9C2 using Cell counting kit (CCK 8). Results: The Myr-5A-Valrubicin nanoparticle formulation was observed to be stable, non-leaky and homogeneous with payload efficiency of 65%, size 87.75 ± 28.4nm, zeta potential -2.89 ± 9.81mV. The percentage hemolysis for Myr-5A-Valrubicin formulation was 5 and 2 times less compared to the free valrubicin formulation at 3.25 and 32.5�g/mL Valrubicin concentration, respectively. The cytotoxicity assays revealed Myr-5A-Valrubicin is effective in protecting cardiomyocytes. Conclusion: These studies indicate the potential of this novel drug delivery platform as an alternative or adjuvant therapy for combating Ewing Sarcoma. More experiments with tumor bearing model are needed to evaluate the efficacy of this formulation before reaching clinic.