Inhibition of xenograft tumor growth in mice by gold nanoparticle-assisted delivery of short hairpin RNAs against Mcl-1L |
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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 |
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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 |
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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. |
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Keywords: | Gold nanoparticle-assisted gene delivery system (AuNP-GDS) Short hairpin RNAs (shRNAs) Xenograft tumor Mcl-1 |
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