Details

Autor(en) / Beteiligte

• Shahzad, Mian M.K
• Mangala, Lingegowda S
• Han, Hee Dong
• Lu, Chunhua
• Bottsford-Miller, Justin
• Nishimura, Masato
• Mora, Edna M
• Lee, Jeong-Won
• Stone, Rebecca L
• Pecot, Chad V
• Thanapprapasr, Duangmani
• Roh, Ju-Won
• Gaur, Puja
• Nair, Maya P
• Park, Yun-Yong
• Sabnis, Nirupama
• Deavers, Michael T
• Lee, Ju-Seog
• Ellis, Lee M
• Lopez-Berestein, Gabriel
• McConathy, Walter J
• Prokai, Laszlo
• Lacko, Andras G
• Sood, Anil K

Titel

Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles

Ist Teil von

• Neoplasia (New York, N.Y.), 2011-04, Vol.13 (4), p.309-IN8

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract RNA interference holds tremendous potential as a therapeutic approach, especially in the treatment of malignant tumors. However, efficient and biocompatible delivery methods are needed for systemic delivery of small interfering RNA (siRNA). To maintain a high level of growth, tumor cells scavenge high-density lipoprotein (HDL) particles by overexpressing its receptor: scavenger receptor type B1 (SR-B1). In this study, we exploited this cellular characteristic to achieve efficient siRNA delivery and established a novel formulation of siRNA by incorporating it into reconstituted HDL (rHDL) nanoparticles. Here, we demonstrate that rHDL nanoparticles facilitate highly efficient systemic delivery of siRNA in vivo , mediated by the SR-B1. Moreover, in therapeutic proof-of-concept studies, these nanoparticles were effective in silencing the expression of two proteins that are key to cancer growth and metastasis (signal transducer and activator of transcription 3 and focal adhesion kinase) in orthotopic mouse models of ovarian and colorectal cancer. These data indicate that an rHDL nanoparticle is a novel and highly efficient siRNA carrier, and therefore, this novel technology could serve as the foundation for new cancer therapeutic approaches.