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.

Public Health Relevance

The purpose of this project is to test a new method for treating acute myeloid leukemia (AML) using a novel red blood cell (RBC) membrane-coated nanoparticle platform. It is known that current treatment protocols for AML are both mentally and physically taxing and time consuming for the patient, mainly because current AML chemotherapy drugs are rapidly cleared from the bloodstream and have narrow therapeutic windows. The proposed project offers a platform that can circulate in the bloodstream for extended periods of time while providing sustained drug release, thus improving treatment efficacy and patient quality of life.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31CA186392-02
Application #
8912271
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Korczak, Jeannette F
Project Start
2014-09-01
Project End
2016-06-30
Budget Start
2015-09-01
Budget End
2016-06-30
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Engineering (All Types)
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Luk, Brian T; Fang, Ronnie H; Hu, Che-Ming J et al. (2016) Safe and Immunocompatible Nanocarriers Cloaked in RBC Membranes for Drug Delivery to Treat Solid Tumors. Theranostics 6:1004-11
Wang, Fei; Fang, Ronnie H; Luk, Brian T et al. (2016) Nanoparticle-Based Antivirulence Vaccine for the Management of Methicillin-Resistant Staphylococcus aureus Skin Infection. Adv Funct Mater 26:1628-1635