Send to

Choose Destination
J Invest Dermatol. 2010 Dec;130(12):2790-8. doi: 10.1038/jid.2010.222. Epub 2010 Aug 5.

Targeted nanoparticles deliver siRNA to melanoma.

Author information

Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.


Melanoma is a severe skin cancer that often leads to death. To examine the potential of small interfering RNA (siRNA) therapy for melanoma, we have developed anisamide-targeted nanoparticles that can systemically deliver siRNA into the cytoplasm of B16F10 murine melanoma cells, which express the sigma receptor. A c-Myc siRNA delivered by the targeted nanoparticles effectively suppressed c-Myc expression in the tumor and partially inhibited tumor growth. More significant tumor growth inhibition was observed with nanoparticles composed of N,N-distearyl-N-methyl-N-2-(N'-arginyl) aminoethyl ammonium chloride (DSAA), a guanidinium-containing cationic lipid, than with a commonly used cationic lipid, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). Three daily injections of c-Myc siRNA formulated in the targeted nanoparticles containing DSAA could impair tumor growth, and the ED(50) of c-Myc siRNA was about 0.55  mg  kg(-1). The targeted DSAA nanoparticles containing c-Myc siRNA sensitized B16F10 cells to paclitaxel (Taxol), resulting in a complete inhibition of tumor growth for 1 week. Treatments of c-Myc siRNA in the targeted nanoparticles containing DSAA also showed significant inhibition on the growth of MDA-MB-435 tumor. The enhanced anti-melanoma activity is probably related to the fact that DSAA, but not DOTAP, induced reactive oxygen species, triggered apoptosis, and downregulated antiapoptotic protein Bcl-2 in B16F10 melanoma cells. Thus, the targeted nanoparticles containing c-Myc siRNA may serve as an effective therapeutic agent for melanoma.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center