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

Fumitaka Takeshita, Yoshiko Minakuchi, Shunji Nagahara, Kimi Honma, Hideo Sasaki, Kotaro Hirai, Takumi Teratani, Nachi Namatame, Yusuke Yamamoto, Koji Hanai, Takashi Kato, Akihiko Sano, Takahiro Ochiya

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    322 Citations (Scopus)

    Abstract

    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-α-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-α 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-mediated systemic delivery method could be a reliable and safe approach to the achievement of maximal function of siRNA.

    Original languageEnglish
    Pages (from-to)12177-12182
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume102
    Issue number34
    DOIs
    Publication statusPublished - 2005 Aug 23

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    Keywords

    • Bone metastasis
    • Prostate cancer

    ASJC Scopus subject areas

    • Genetics
    • General

    Cite this

    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. (2005). Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo. Proceedings of the National Academy of Sciences of the United States of America, 102(34), 12177-12182. https://doi.org/10.1073/pnas.0501753102