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Inhibition of xenograft tumor growth in mice by gold nanoparticle-assisted delivery of short hairpin RNAs against Mcl-1L
Authors:Ryou Sang-Mi  Park Mira  Kim Jong-Myung  Jeon Che Ok  Yun Cheol-Hui  Han Seung Hyun  Kim Si Wouk  Lee Younghoon  Kim Sudeok  Han Min Su  Bae Jeehyeon  Lee Kangseok
Institution:a Department of Pharmacy, College of Pharmacy, CHA University, Seongnam 463-836, Republic of Korea
b School of Biological Sciences, Chung-Ang University, Seoul 156-756, Republic of Korea
c Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea
d Department of Oral Microbiology and Immunology, Dental Research Institute, and BK21 Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea
e Department of Environmental Engineering, Chosun University, Gwangju 501-759, Republic of Korea
f Department of Chemistry, KAIST, Daejeon 305-701, Republic of Korea
g Department of Chemistry, Chung-Ang University, Seoul 156-756, Republic of Korea
Abstract:A prerequisite for the therapeutic use of small RNAs is the development of a method that can deliver them into animals. Previous studies have shown the capability of functionalized gold nanoparticles to serve as a general platform for loading and delivering DNA oligonucleotides and short hairpin RNAs (shRNAs) into cultured human cells. Here, we report the ability of the gold nanoparticle-assisted gene delivery system (AuNP-GDS) to deliver shRNA to a xenograft tumor in a mouse model. AuNP-GDS delivery of in vitro synthesized shRNA targeted to the Mcl-1L gene knocked down levels of Mcl-1L mRNA and protein by ∼36% and ∼26%, respectively, which were sufficient to induce apoptosis of the xenograft tumor cells and consequently inhibited the development of the tumor. We demonstrated that our lego-like AuNP-GDS, which can easily load and deliver shRNAs targeted to any gene of interest into living systems, can deliver shRNAs into xenograft tumors, leading to antitumor activity in an animal model.
Keywords:Gold nanoparticle-assisted gene delivery system (AuNP-GDS)  Short hairpin RNAs (shRNAs)  Xenograft tumor  Mcl-1
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