Abstract 3202: Investigating the induction of ferroptosis by nano drug delivery system

Abstract

Abstract Prostate cancer is the second leading cause of cancer-related death in U.S. men. Genomic and clinical associations have identified loss of RB function as a dominant mechanism driving prostate cancer lethality. We recently demonstrated that ferroptosis induction in vivo by ferroptosis inducers blocks RB1-deficient prostate tumor growth and metastasis and leads to improved survival of the mice. As all ferroptosis inducers are newly discovered, there is a great need to improve their therapeutic potential through different avenues, including innovative drug delivery systems. Poly Lactic-co-glycolic acid (PLGA) is an FDA-approved biodegradable polymer. Due to their strong biocompatibility and consistent release, PLGA-based nanotherapeutics are an attractive carrier for small molecule drugs. This study aims to further improve the efficacy of ferroptosis induction against lethal RB1-deficient prostate cancer through PLGA-based ferroptosis-induced nanoparticles (NPs). The PLGA NPs encapsulating JKE-1674 were synthesized using the solvent evaporation method. The NPs were characterized using dynamic light scattering (DLS) and scanning electron microscopy (SEM) to assess the physicochemical properties of the NPs. The cell-killing efficacy of free-form or PLGA NP encapsulated JKE-1674 was then evaluated in vitro. Our analyses showed that the particle size and polydispersity index (PDI) of JKE-1674 PLGA NPs were 160.8 nm and 0.049, respectively. SEM images of JKE-1674 PLGA NPs further validated the DLS data. These findings suggest that encapsulation of JKE-1674 within the PLGA NPs results in a stable and biocompatible formation. Critically, JKE-1674 encapsulated by PLGA NPs is as potent as JKE-1674 in its free form to induce ferroptosis and associated lipid peroxidation in various human prostate cancer cell lines. This study presents the first effort to develop and validate PLGA-based ferroptosis-induced nanotherapeutics. Based on our in vitro data, we will test the in vivo efficacy of JKE-1674 PLGA NPs against lethal RB1 deficient prostate cancer. Citation Format: Eden M. Jacob, Sarah Y. Kim, Parul Sirohi, Mu-En Wang, Meredith L. Davis, Alyssa R. Bawcom, Ashutosh Chilkoti, Mark R. Wiesner, Jiaoti Huang, Ming Chen. Investigating the induction of ferroptosis by nano drug delivery system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3202.