Improving Delivery of RNA to Leukemia Cells Using Polymeric Nanoparticles

Researcher(s)

  • Laura Weinstein, Biomedical Engineering, University of Delaware

Faculty Mentor(s)

  • Emily Day, Biomedical Engineering, University of Delaware

Abstract

Acute megakaryoblastic leukemia (AMKL) results from the abnormal proliferation of megakaryocyte progenitors, the precursors to red blood cells. The 1-year survival rate for adults diagnosed with AMKL is only 17.6%. In AMKL , transforming growth factor beta is a hallmark protein contributing to this cytogenetic malfunction. Protein synthesis is regulated by various types of RNA that can either promote or inhibit protein production within cells. Silencing RNA (siRNA) modulates gene expression by binding to messenger RNAs (mRNAs) with complementary sequences, leading to their degradation and preventing the translation of the corresponding protein. Delivering siRNA directly to AMKL cells is hypothesized to induce cell death. Additionally, studies indicate that encapsulating siRNA within polymeric nanoparticles composed of poly(lactic-co-glycolic acid) (PLGA) enhances efficacy due to the nanoparticles’ low toxicity, high bioavailability, controlled drug release, and targeted action on lesions via multiple drug delivery routes. The objective of this project was to reduce the viability of AMKL cells through the delivery of siRNA encapsulated in PLGA nanoparticles, thereby providing a novel therapeutic approach for combating leukemia.