Systemic delivery of siRNA by actively targeted polyion complex micelles for silencing the E6 and E7 human papillomavirus oncogenes

Haruka Nishida; Yoko Matsumoto; Kei Kawana; R. James Christie; Mitsuru Naito; Beob Soo Kim; Kazuko Toh; Hyun Su Min; Yu Yi; Yu Matsumoto; Hyun Jin Kim; Kanjiro Miyata; Ayumi Taguchi; Kensuke Tomio; Aki Yamashita; Tomoko Inoue; Hiroe Nakamura; Asaha Fujimoto; Masakazu Sato; Mitsuyo Yoshida; Katsuyuki Adachi; Takahide Arimoto; Osamu Wada-Hiraike; Katsutoshi Oda; Takeshi Nagamatsu; Nobuhiro Nishiyama; Kazunori Kataoka; Yutaka Osuga; Tomoyuki Fujii

doi:10.1016/j.jconrel.2016.03.016

Systemic delivery of siRNA by actively targeted polyion complex micelles for silencing the E6 and E7 human papillomavirus oncogenes

Haruka Nishida, Yoko Matsumoto, Kei Kawana, R. James Christie, Mitsuru Naito, Beob Soo Kim, Kazuko Toh, Hyun Su Min, Yu Yi, Yu Matsumoto, Hyun Jin Kim, Kanjiro Miyata, Ayumi Taguchi, Kensuke Tomio, Aki Yamashita, Tomoko Inoue, Hiroe Nakamura, Asaha Fujimoto, Masakazu Sato, Mitsuyo YoshidaKatsuyuki Adachi, Takahide Arimoto, Osamu Wada-Hiraike, Katsutoshi Oda, Takeshi Nagamatsu, Nobuhiro Nishiyama, Kazunori Kataoka, Yutaka Osuga, Tomoyuki Fujii

Research output: Contribution to journal › Article › peer-review

50 Scopus citations

Abstract

Human papillomavirus (HPV) E6 and E7 oncogenes are essential for the immortalization and maintenance of HPV-associated cancer and are ubiquitously expressed in cervical cancer lesions. Small interfering RNA (siRNA) coding for E6 and E7 oncogenes is a promising approach for precise treatment of cervical cancer, yet a delivery system is required for systemic delivery to solid tumors. Here, an actively targeted polyion complex (PIC) micelle was applied to deliver siRNAs coding for HPV E6/E7 to HPV cervical cancer cell tumors in immune-incompetent tumor-bearing mice. A cell viability assay revealed that both HPV type 16 and 18 E6/E7 siRNAs (si16E6/E7 and si18E6/E7, respectively) interfered with proliferation of cervical cancer cell lines in an HPV type-specific manner. A fluorescence imaging biodistribution analysis further revealed that fluorescence dye-labeled siRNA-loaded PIC micelles efficiently accumulated within the tumor mass after systemic administration. Ultimately, intravenous injection of si16E6/E7 and si18E6/E7-loaded PIC micelles was found to significantly suppress the growth of subcutaneous SiHa and HeLa tumors, respectively. The specific activity of siRNA treatment was confirmed by the observation that p53 protein expression was restored in the tumors excised from the mice treated with si16E6/E7- and si18E6/E7-loaded PIC micelles for SiHa and HeLa tumors, respectively. Therefore, the actively targeted PIC micelle incorporating HPV E6/E7-coding siRNAs demonstrated its therapeutic potential against HPV-associated cancer.

Original language	English
Pages (from-to)	29-37
Number of pages	9
Journal	Journal of Controlled Release
Volume	231
DOIs	https://doi.org/10.1016/j.jconrel.2016.03.016
State	Published - 10 Jun 2016
Externally published	Yes

Keywords

Cervical cancer
Drug delivery system
Human papillomavirus (HPV) E6/E7
Polyion complex (PIC) micelle
Small interfering RNA (siRNA)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jconrel.2016.03.016

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Nishida, H., Matsumoto, Y., Kawana, K., Christie, R. J., Naito, M., Kim, B. S., Toh, K., Min, H. S., Yi, Y., Matsumoto, Y., Kim, H. J., Miyata, K., Taguchi, A., Tomio, K., Yamashita, A., Inoue, T., Nakamura, H., Fujimoto, A., Sato, M., ... Fujii, T. (2016). Systemic delivery of siRNA by actively targeted polyion complex micelles for silencing the E6 and E7 human papillomavirus oncogenes. Journal of Controlled Release, 231, 29-37. https://doi.org/10.1016/j.jconrel.2016.03.016

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title = "Systemic delivery of siRNA by actively targeted polyion complex micelles for silencing the E6 and E7 human papillomavirus oncogenes",

abstract = "Human papillomavirus (HPV) E6 and E7 oncogenes are essential for the immortalization and maintenance of HPV-associated cancer and are ubiquitously expressed in cervical cancer lesions. Small interfering RNA (siRNA) coding for E6 and E7 oncogenes is a promising approach for precise treatment of cervical cancer, yet a delivery system is required for systemic delivery to solid tumors. Here, an actively targeted polyion complex (PIC) micelle was applied to deliver siRNAs coding for HPV E6/E7 to HPV cervical cancer cell tumors in immune-incompetent tumor-bearing mice. A cell viability assay revealed that both HPV type 16 and 18 E6/E7 siRNAs (si16E6/E7 and si18E6/E7, respectively) interfered with proliferation of cervical cancer cell lines in an HPV type-specific manner. A fluorescence imaging biodistribution analysis further revealed that fluorescence dye-labeled siRNA-loaded PIC micelles efficiently accumulated within the tumor mass after systemic administration. Ultimately, intravenous injection of si16E6/E7 and si18E6/E7-loaded PIC micelles was found to significantly suppress the growth of subcutaneous SiHa and HeLa tumors, respectively. The specific activity of siRNA treatment was confirmed by the observation that p53 protein expression was restored in the tumors excised from the mice treated with si16E6/E7- and si18E6/E7-loaded PIC micelles for SiHa and HeLa tumors, respectively. Therefore, the actively targeted PIC micelle incorporating HPV E6/E7-coding siRNAs demonstrated its therapeutic potential against HPV-associated cancer.",

keywords = "Cervical cancer, Drug delivery system, Human papillomavirus (HPV) E6/E7, Polyion complex (PIC) micelle, Small interfering RNA (siRNA)",

author = "Haruka Nishida and Yoko Matsumoto and Kei Kawana and Christie, \{R. James\} and Mitsuru Naito and Kim, \{Beob Soo\} and Kazuko Toh and Min, \{Hyun Su\} and Yu Yi and Yu Matsumoto and Kim, \{Hyun Jin\} and Kanjiro Miyata and Ayumi Taguchi and Kensuke Tomio and Aki Yamashita and Tomoko Inoue and Hiroe Nakamura and Asaha Fujimoto and Masakazu Sato and Mitsuyo Yoshida and Katsuyuki Adachi and Takahide Arimoto and Osamu Wada-Hiraike and Katsutoshi Oda and Takeshi Nagamatsu and Nobuhiro Nishiyama and Kazunori Kataoka and Yutaka Osuga and Tomoyuki Fujii",

year = "2016",

month = jun,

day = "10",

doi = "10.1016/j.jconrel.2016.03.016",

language = "英語",

volume = "231",

pages = "29--37",

journal = "Journal of Controlled Release",

issn = "0168-3659",

publisher = "Elsevier B.V.",

}

Nishida, H, Matsumoto, Y, Kawana, K, Christie, RJ, Naito, M, Kim, BS, Toh, K, Min, HS, Yi, Y, Matsumoto, Y, Kim, HJ, Miyata, K, Taguchi, A, Tomio, K, Yamashita, A, Inoue, T, Nakamura, H, Fujimoto, A, Sato, M, Yoshida, M, Adachi, K, Arimoto, T, Wada-Hiraike, O, Oda, K, Nagamatsu, T, Nishiyama, N, Kataoka, K, Osuga, Y & Fujii, T 2016, 'Systemic delivery of siRNA by actively targeted polyion complex micelles for silencing the E6 and E7 human papillomavirus oncogenes', Journal of Controlled Release, vol. 231, pp. 29-37. https://doi.org/10.1016/j.jconrel.2016.03.016

TY - JOUR

T1 - Systemic delivery of siRNA by actively targeted polyion complex micelles for silencing the E6 and E7 human papillomavirus oncogenes

AU - Nishida, Haruka

AU - Matsumoto, Yoko

AU - Kawana, Kei

AU - Christie, R. James

AU - Naito, Mitsuru

AU - Kim, Beob Soo

AU - Toh, Kazuko

AU - Min, Hyun Su

AU - Yi, Yu

AU - Matsumoto, Yu

AU - Kim, Hyun Jin

AU - Miyata, Kanjiro

AU - Taguchi, Ayumi

AU - Tomio, Kensuke

AU - Yamashita, Aki

AU - Inoue, Tomoko

AU - Nakamura, Hiroe

AU - Fujimoto, Asaha

AU - Sato, Masakazu

AU - Yoshida, Mitsuyo

AU - Adachi, Katsuyuki

AU - Arimoto, Takahide

AU - Wada-Hiraike, Osamu

AU - Oda, Katsutoshi

AU - Nagamatsu, Takeshi

AU - Nishiyama, Nobuhiro

AU - Kataoka, Kazunori

AU - Osuga, Yutaka

AU - Fujii, Tomoyuki

PY - 2016/6/10

Y1 - 2016/6/10

N2 - Human papillomavirus (HPV) E6 and E7 oncogenes are essential for the immortalization and maintenance of HPV-associated cancer and are ubiquitously expressed in cervical cancer lesions. Small interfering RNA (siRNA) coding for E6 and E7 oncogenes is a promising approach for precise treatment of cervical cancer, yet a delivery system is required for systemic delivery to solid tumors. Here, an actively targeted polyion complex (PIC) micelle was applied to deliver siRNAs coding for HPV E6/E7 to HPV cervical cancer cell tumors in immune-incompetent tumor-bearing mice. A cell viability assay revealed that both HPV type 16 and 18 E6/E7 siRNAs (si16E6/E7 and si18E6/E7, respectively) interfered with proliferation of cervical cancer cell lines in an HPV type-specific manner. A fluorescence imaging biodistribution analysis further revealed that fluorescence dye-labeled siRNA-loaded PIC micelles efficiently accumulated within the tumor mass after systemic administration. Ultimately, intravenous injection of si16E6/E7 and si18E6/E7-loaded PIC micelles was found to significantly suppress the growth of subcutaneous SiHa and HeLa tumors, respectively. The specific activity of siRNA treatment was confirmed by the observation that p53 protein expression was restored in the tumors excised from the mice treated with si16E6/E7- and si18E6/E7-loaded PIC micelles for SiHa and HeLa tumors, respectively. Therefore, the actively targeted PIC micelle incorporating HPV E6/E7-coding siRNAs demonstrated its therapeutic potential against HPV-associated cancer.

AB - Human papillomavirus (HPV) E6 and E7 oncogenes are essential for the immortalization and maintenance of HPV-associated cancer and are ubiquitously expressed in cervical cancer lesions. Small interfering RNA (siRNA) coding for E6 and E7 oncogenes is a promising approach for precise treatment of cervical cancer, yet a delivery system is required for systemic delivery to solid tumors. Here, an actively targeted polyion complex (PIC) micelle was applied to deliver siRNAs coding for HPV E6/E7 to HPV cervical cancer cell tumors in immune-incompetent tumor-bearing mice. A cell viability assay revealed that both HPV type 16 and 18 E6/E7 siRNAs (si16E6/E7 and si18E6/E7, respectively) interfered with proliferation of cervical cancer cell lines in an HPV type-specific manner. A fluorescence imaging biodistribution analysis further revealed that fluorescence dye-labeled siRNA-loaded PIC micelles efficiently accumulated within the tumor mass after systemic administration. Ultimately, intravenous injection of si16E6/E7 and si18E6/E7-loaded PIC micelles was found to significantly suppress the growth of subcutaneous SiHa and HeLa tumors, respectively. The specific activity of siRNA treatment was confirmed by the observation that p53 protein expression was restored in the tumors excised from the mice treated with si16E6/E7- and si18E6/E7-loaded PIC micelles for SiHa and HeLa tumors, respectively. Therefore, the actively targeted PIC micelle incorporating HPV E6/E7-coding siRNAs demonstrated its therapeutic potential against HPV-associated cancer.

KW - Cervical cancer

KW - Drug delivery system

KW - Human papillomavirus (HPV) E6/E7

KW - Polyion complex (PIC) micelle

KW - Small interfering RNA (siRNA)

UR - http://www.scopus.com/inward/record.url?scp=84977955875&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2016.03.016

DO - 10.1016/j.jconrel.2016.03.016

M3 - 記事

C2 - 26979870

AN - SCOPUS:84977955875

SN - 0168-3659

VL - 231

SP - 29

EP - 37

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -

Systemic delivery of siRNA by actively targeted polyion complex micelles for silencing the E6 and E7 human papillomavirus oncogenes

Abstract

Keywords

UN SDGs

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