Lipoprotein Based Targeted Therapy for AML

Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults; it is only cured in less than 50% of the patients that are diagnosed with the disease. A new approach to the AML treatment is proposed using a nanoparticle system (rHDL) that mimics the structure and function of endogenous high density lipoproteins (HDL) specifically targeting the scavenger receptor type B1 [SR-B1] that is overexpressed in cancer cells. The drug-rHDL complex would be more efficient in specifically delivering the anti-cancer drugs to its target. Objective: Create a new drug delivery system for AML chemotherapy by formulating rHDL nanoparticles with current AML pharmaceutical drugs (e.g. etoposide and azacitadine) for preclinical studies. Method: Revising the existing protocol for rHDL nanoparticle synthesis from Lipoprotein Drug Delivery Research Laboratory at UNTHSC, etoposide was encapsulated in rHDL nanoparticles and left to be characterized. Characterization involved using the high performance liquid chromatography (HPLC) instrument to analyze the compound and the drug content within the nanoparticles. Nanoparticle size, zeta potential and composition will be determined using established methods in the lab. Revisions to the synthesis protocol will be made accordingly in order to maximize the amount of drug encapsulated. Conclusions: A standard curve has been established to characterize the nanoparticle-drug loading created by utilizing high performance liquid chromatography (HPLC). Current work involves characterizing the rHDL nanoparticles for drug loading and physical attributes such as size, zeta potential and chemical composition. After characterization and revising the protocol to maximize the drug content within the nanoparticles, the next step in the process would involve evaluating cytotoxicity in SR-B1 positive AML cells before moving to animal models. The long term goal of the project is to create a new delivery method for AML in order to minimize the side effects and enhance the therapeutic index of multiple AML drugs used in management of AML.