Targeted Erythrocyte Membrane-Coated Nanoparticles for the Treatment of AML

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DESCRIPTION (provided by applicant): Acute myeloid leukemia (AML) is the most common acute leukemia that affects adults, with an estimated 13,780 new cases and 10,200 deaths in 2012. 54% of patients are diagnosed at 65 years or older, with the incidence of AML increasing with age. Thus, AML is becoming a progressively important issue as the population ages. Current therapies are extremely intensive and both mentally and physically draining on the patient, necessitating the need for a more effective and efficient mode of treatment. The objective of this project is to overcome this hurdle using a novel red blood cell membrane-coated polymer nanoparticle (RBC-NP) platform. This formulation will not only offer sustained delivery of chemotherapy drugs, but more importantly will specifically target leukemia cells and preferentially eliminate the cancerous cells. Aims: 1) To synthesize and optimize RBC-NPs as long-circulating delivery vehicles for sustained release of chemotherapy drugs to treat AML in vitro and in vivo. 2) To synthesize and test half-antibody functionalized RBC membrane-coated polymeric nanoparticles for targeted drug delivery in vivo to a human AML model in mice. Conclusion: Improving the therapeutic efficacy of chemotherapy and increasing leukemia-specific toxicity of therapeutic drugs remains important in the treatment of AML. It is critical to effectively treat patients while inducing minimal adverse side effects, thereby improving their quality of life. Current treatment methods for AML involve drugs with narrow therapeutic windows and short blood elimination half-lives. It is hypothesized that by extending the circulation half-life of chemotherapeutic drugs and controlling their release, the plasma drug concentration can be more reliably controlled, thereby more effectually treating AML.