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Targeted Delivery of Small Interfering RNA: Approaching Effective Cancer Therapies

Department of Oncology, Georgetown University Medical Center, Washington, District of Columbia

Requests for reprints: Esther H. Chang, Department of Oncology, Georgetown University Medical Center, TRB/E420, 3970 Reservoir Road Northwest, Washington, DC 20057-1469. Phone: 202-687-8418; Fax: 202-687-8434; E-mail: change{at}georgetown.edu.

Key Words: siRNA • anticancer therapy • systemic delivery • targeted delivery

Three of the primary requirements for the development of effective dual-targeting therapeutic modalities for the treatment of cancer are the tumor-targeted delivery of the therapeutic molecules of interest to the tumor site(s) in the body (both primary and metastatic), passage of the molecular therapeutic through the cell membrane, and targeting specifically a growth or apoptotic pathway. However, lack of efficient targeted delivery, low transfection efficiency, instability to nucleases, poor tissue penetration, and nonspecific immune stimulation have hindered the translation of small interfering RNA (siRNA) into clinical applications. The development of a systemically administered, tumor-specific immunoliposome nanocomplex with high transfection efficiency could overcome these limitations and thus realize the potential of siRNAs to become effective anticancer clinical modalities. [Cancer Res 2008;68(5):1247–50]