Polymeric micelles for MRI-visible targeted drug delivery

COLL 216

Norased Nasongkla, norased@hotmail.com1, Erik Bey, eric.bey@utsouthwestern.edu2, Jimin Ren, jinmin.ren@utsouthwestern.edu3, Chalermchai Khemtong, chalermchai.khemtong@utsouthwestern.edu2, A. Dean Sherry, Dean.Sherry@UTSouthwestern.edu4, Shook-Fong Chin, schin@utdallas.edu2, David A. Boothman, david.boothman@utsouthwestern.edu2, and Jinming Gao, jinming.gao@utsouthwestern.edu2. (1) Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH 44106, (2) Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, dallas, TX 75390, (3) Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, dallas, TX 75390, (4) Advanced Imaging Research Center, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390-8568
Multifunctional nanomedicine has received significant attention as an integrated platform for drug delivery and diagnostic imaging applications. Incorporation of multiple functions (e.g. cancer targeting, imaging ultrasensitivity, controlled drug release) within such a small size confinement (<100 nm) is a challenging task. In this application, we develop multifunctional targeted delivery superparamagnetic polymeric micelles comprising of three key components: (1) doxorubicin (DOXO) as an anti-cancer agent; (2) cyclic pentapeptide (cRGD) ligand that targets alpha-v-beta-3 integrin on angiogenic tumor endothelial cells; and (3) superparamagnetic iron oxide (SPIO) nanoparticles as a magnetic resonance imaging (MRI) probe. SPIO nanoparicles and DOXO are incorporated inside hydrophobic micelle core. cRGD is attached to the micelle surface. Cell uptake enhancement by receptor based-endocytosis of cRGD-DOXO-SPIO-loaded micelles is evaluated by in vitro cytotoxicity study, flow cytometry, confocal laser microscopy and MRI. This work will open many exciting opportunities for the targeted delivery of cytotoxic therapeutic agents to cancerous tumors and use of MRI as a non-invasive strategy to monitor the tumor targeting efficiency to improve the therapeutic outcome of drug therapy.
 

Advances in Nanomedicine
1:30 PM-5:20 PM, Monday, 11 September 2006 Sir Francis Drake -- Monterey/Cypress Rooms, Oral

Division of Colloid & Surface Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006