ENHANCED TARGETING OF MEGAKARYOBLASTIC LEUKEMIA BY CANCER CELL MEMBRANE-WRAPPED POLYMER NANOPARTICLES TO INHIBIT β-CATENIN THROUGH SIRNA DELIVERY

Abstract

Acute megakaryoblastic leukemia (AMKL) is a rare and aggressive form of leukemia characterized by an overabundance of β-catenin signaling, which contributes to leukemogenesis and therapeutic resistance. Small interfering RNA (siRNA) offers a targeted approach to silencing oncogenic drivers like β-catenin, but its clinical application remains limited due to delivery challenges. This thesis focuses on the development and optimization of polymeric nanoparticles for the targeted delivery of β-catenin siRNA into AMKL cells. Sixteen unique nanoparticle formulations were synthesized and systematically characterized based on hydrodynamic diameter, ζ potential, and encapsulation efficiency. These formulations were evaluated for their cellular uptake efficiency in AMKL cells, cytocompatibility via Alamar Blue assay, and gene silencing of β-catenin using immunofluorescent flow cytometry. Results identified lead formulations capable of efficient siRNA encapsulation and intracellular delivery, with significant downregulation of β-catenin. This work demonstrates the feasibility of using polymeric nanoparticles as a vehicle for RNA interference-based therapy in AMKL and lays the groundwork for future studies focused on in vivo delivery, long-term therapeutic efficacy, and immune compatibility.