Journal
JOURNAL OF PHARMACEUTICAL INNOVATION
Volume 9, Issue 2, Pages 158-173Publisher
SPRINGER
DOI: 10.1007/s12247-014-9183-4
Keywords
Gene silencing; siRNA delivery; Tumor accumulation and penetration; Cell uptake; Endosome escape; Liposomes; Polymeric nanoparticles; Inorganic nanoparticles
Categories
Funding
- National Institutes of Health [A1081218]
- Juvenile Diabetes Research Foundation
- Pennsylvania Department of Health through the Commonwealth Universal Research Enhancement Program
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Small-interfering RNA (siRNA) is both a powerful tool in research and a promising therapeutic platform to modulate expression of disease-related genes. Malignant tumors are attractive disease targets for nucleic acid-based therapies. siRNA directed against oncogenes, and genes driving metastases or angiogenesis have been evaluated in animal models and in some cases, in humans. The outcomes of these studies indicate that drug delivery is a significant limiting factor. This review provides perspectives on in vivo validated nanoparticle-based siRNA delivery systems. Results of recent advances in liposomes and polymeric and inorganic formulations illustrate the need for mutually optimized attributes for performance in systemic circulation, tumor interstitial space, plasma membrane, and endosomes. Physiochemical properties conducive to efficient siRNA delivery are summarized and directions for future research are discussed.
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