Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo

被引:310
作者
Takeshita, F
Minakuchi, Y
Nagahara, S
Honma, K
Sasaki, H
Hirai, K
Teratani, T
Namatame, N
Yamamoto, Y
Hanai, K
Kato, T
Sano, A
Ochiya, T
机构
[1] Natl Canc Ctr, Inst Res, Sect Studies Metastasis, Chuo Ku, Tokyo 1040045, Japan
[2] Sumitomo Pharmaceut Co Ltd, Formulat Res Labs, Osaka 5670878, Japan
[3] Keken Biosci Inst, Tokyo 1150051, Japan
[4] Waseda Univ, Sch Educ, Dept Biol, Tokyo 1690051, Japan
关键词
bone metastasis; prostate cancer;
D O I
10.1073/pnas.0501753102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery for siRNAs toward treatment of bone-metastatic cancer. Accordingly, we report here that i.v. injection of GL3 luciferase siRNA complexed with atelocollagen showed effective reduction of luciferase expression from bone-metastatic prostate tumor cells developed in mouse thorax, jaws, and/or legs. We also show that the siRNA/atelocollagen complex can be efficiently delivered to tumors 24 h after injection and can exist intact at least for 3 days. Furthermore, atelocollagen-mediated systemic administration of siRNAs such as enhancer of zeste homolog 2 and phosphoinositide 3'-hydroxykinase p110-alpha-subunit, which were selected as candidate targets for inhibition of bone metastasis, resulted in an efficient inhibition of metastatic tumor growth in bone tissues. In addition, upregulation of serum IL-12 and IFN-alpha levels was not associated with the in vivo administration of the siRNA/atelocollagen complex. Thus, for treatment of bone metastasis of prostate cancer, an atelocollagen-miediated systemic delivery method could be a reliable and safe approach to the achievement of maximal function of siRNA.
引用
收藏
页码:12177 / 12182
页数:6
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