DOI: 10.1073/pnas.0501753102. Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen <i>in vivo</i>

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

10.1073/pnas.0501753102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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.

Bibliography

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, 102(34), 12177â12182.

Authors 13

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

References 37 Referenced 309

10.1038/nature02870
10.1038/418038a
10.1038/ng944
10.1016/S1535-6108(02)00122-8
10.1038/nbt739
10.1016/S0022-2836(03)00181-5
10.1261/rna.5239604
10.1038/nature03121
Verma, U. N., Surabhi, R. M., Schmaltieg, A., Becerra, C. & Gaynor, R. B. (2003) Clin. Cancer Res. 9, 1291-1300.12684397 / Clin. Cancer Res. (2003)
Filleur, S., Courtin, A., Ait-Si-Ali, S., Guglielmi, J., Merle, C., Harel-Bellan, A., Clezardin, P. & Cabon, F. (2003) Cancer Res. 63, 3919-3922.12873985 / Cancer Res. (2003)
10.1016/j.bbrc.2003.10.060
10.1038/sj.onc.1207247
10.1093/jnci/djh146
10.1038/9560
10.1006/bbrc.2001.6133
10.2174/1566523013348887
10.1002/jgm.440
10.1016/j.addr.2003.08.005
10.1089/104303404322886110
Minakuchi, Y., Takeshita, F., Kosaka, N., Sasaki, H., Yamamoto, Y., Kouno, M., Honma, K., Nagahara, S., Hanai, K., Sano, A., et al. (2004) Nucleic Acids Res. 32, e109.15272050 (10.1093/nar/gnh093) / Nucleic Acids Res. (2004)
10.1158/0008-5472.CAN-03-2682
10.1146/annurev.bb.03.060174.001311
10.1038/35078107
Arguello, F., Furlanetto, R. W., Baggs, R. B., Graves, B. T., Harwell, S. E., Cohen, H. J. & Frantz, C. N. (1992) Cancer Res. 52, 2304-2309.1559233 / Cancer Res. (1992)
10.1023/B:CLIN.0000006817.25962.87
10.1023/B:CLIN.0000006815.49932.98
Scanlon, K. J. (2004) Anticancer Res. 24, 501-504.15152950 / Anticancer Res. (2004)
10.1016/j.bbrc.2003.11.057
10.1038/nbt831
10.1038/ng1173
10.1038/nbt1038
10.2165/00003088-200342130-00002
10.1038/nm1002
10.1038/nature01075
10.1146/annurev.cellbio.17.1.615
10.1073/pnas.1933744100
10.4161/cbt.3.8.994

Dates

Type	When
Created	20 years ago (Aug. 9, 2005, 10:53 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 2:21 p.m.)
Indexed	4 days ago (Aug. 26, 2025, 2:29 a.m.)
Issued	20 years ago (Aug. 9, 2005)
Published	20 years ago (Aug. 9, 2005)
Published Online	20 years ago (Aug. 9, 2005)
Published Print	20 years ago (Aug. 23, 2005)

Funders 0

None

BibTeX

@article{Takeshita_2005, title={Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0501753102}, DOI={10.1073/pnas.0501753102}, number={34}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Takeshita, Fumitaka and Minakuchi, Yoshiko and Nagahara, Shunji and Honma, Kimi and Sasaki, Hideo and Hirai, Kotaro and Teratani, Takumi and Namatame, Nachi and Yamamoto, Yusuke and Hanai, Koji and Kato, Takashi and Sano, Akihiko and Ochiya, Takahiro}, year={2005}, month=aug, pages={12177–12182} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        26
      ]
    ],
    "date-time": "2025-08-26T06:29:01Z",
    "timestamp": 1756189741570
  },
  "reference-count": 37,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "34",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2005,
        8,
        23
      ]
    ]
  },
  "abstract": "<jats:p>\n            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\u2032-hydroxykinase p110-\u03b1-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-\u03b1 levels was not associated with the\n            <jats:italic>in vivo</jats:italic>\n            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.\n          </jats:p>",
  "DOI": "10.1073/pnas.0501753102",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2005,
        8,
        10
      ]
    ],
    "date-time": "2005-08-10T02:53:29Z",
    "timestamp": 1123642409000
  },
  "page": "12177-12182",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 309,
  "title": "Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen\n            <i>in vivo</i>",
  "prefix": "10.1073",
  "volume": "102",
  "author": [
    {
      "given": "Fumitaka",
      "family": "Takeshita",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    },
    {
      "given": "Yoshiko",
      "family": "Minakuchi",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    },
    {
      "given": "Shunji",
      "family": "Nagahara",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    },
    {
      "given": "Kimi",
      "family": "Honma",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    },
    {
      "given": "Hideo",
      "family": "Sasaki",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    },
    {
      "given": "Kotaro",
      "family": "Hirai",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    },
    {
      "given": "Takumi",
      "family": "Teratani",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    },
    {
      "given": "Nachi",
      "family": "Namatame",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    },
    {
      "given": "Yusuke",
      "family": "Yamamoto",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    },
    {
      "given": "Koji",
      "family": "Hanai",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    },
    {
      "given": "Takashi",
      "family": "Kato",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    },
    {
      "given": "Akihiko",
      "family": "Sano",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    },
    {
      "given": "Takahiro",
      "family": "Ochiya",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2005,
        8,
        9
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature02870"
    },
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/418038a"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng944"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1535-6108(02)00122-8"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nbt739"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0022-2836(03)00181-5"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1261/rna.5239604"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature03121"
    },
    {
      "key": "e_1_3_2_9_2",
      "first-page": "1291",
      "volume": "9",
      "year": "2003",
      "unstructured": "Verma, U. N., Surabhi, R. M., Schmaltieg, A., Becerra, C. & Gaynor, R. B. (2003) Clin. Cancer Res. 9, 1291-1300.12684397",
      "journal-title": "Clin. Cancer Res."
    },
    {
      "key": "e_1_3_2_10_2",
      "first-page": "3919",
      "volume": "63",
      "year": "2003",
      "unstructured": "Filleur, S., Courtin, A., Ait-Si-Ali, S., Guglielmi, J., Merle, C., Harel-Bellan, A., Clezardin, P. & Cabon, F. (2003) Cancer Res. 63, 3919-3922.12873985",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.bbrc.2003.10.060"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.onc.1207247"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/jnci/djh146"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/9560"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/bbrc.2001.6133"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.2174/1566523013348887"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jgm.440"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.addr.2003.08.005"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1089/104303404322886110"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "crossref",
      "first-page": "e109",
      "DOI": "10.1093/nar/gnh093",
      "volume": "32",
      "year": "2004",
      "unstructured": "Minakuchi, Y., Takeshita, F., Kosaka, N., Sasaki, H., Yamamoto, Y., Kouno, M., Honma, K., Nagahara, S., Hanai, K., Sano, A., et al. (2004) Nucleic Acids Res. 32, e109.15272050",
      "journal-title": "Nucleic Acids Res."
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1158/0008-5472.CAN-03-2682"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.bb.03.060174.001311"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35078107"
    },
    {
      "key": "e_1_3_2_24_2",
      "first-page": "2304",
      "volume": "52",
      "year": "1992",
      "unstructured": "Arguello, F., Furlanetto, R. W., Baggs, R. B., Graves, B. T., Harwell, S. E., Cohen, H. J. & Frantz, C. N. (1992) Cancer Res. 52, 2304-2309.1559233",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1023/B:CLIN.0000006817.25962.87"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1023/B:CLIN.0000006815.49932.98"
    },
    {
      "key": "e_1_3_2_27_2",
      "first-page": "501",
      "volume": "24",
      "year": "2004",
      "unstructured": "Scanlon, K. J. (2004) Anticancer Res. 24, 501-504.15152950",
      "journal-title": "Anticancer Res."
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.bbrc.2003.11.057"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nbt831"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng1173"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nbt1038"
    },
    {
      "key": "e_1_3_2_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.2165/00003088-200342130-00002"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nm1002"
    },
    {
      "key": "e_1_3_2_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature01075"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.cellbio.17.1.615"
    },
    {
      "key": "e_1_3_2_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.1933744100"
    },
    {
      "key": "e_1_3_2_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.4161/cbt.3.8.994"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.0501753102",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        12
      ]
    ],
    "date-time": "2022-04-12T18:21:13Z",
    "timestamp": 1649787673000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.0501753102"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2005,
        8,
        9
      ]
    ]
  },
  "references-count": 37,
  "journal-issue": {
    "issue": "34",
    "published-print": {
      "date-parts": [
        [
          2005,
          8,
          23
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.0501753102"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.0501753102",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2005,
        8,
        9
      ]
    ]
  },
  "assertion": [
    {
      "value": "2005-03-03",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2005-08-09",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}