Selective delivery of PLXDC1 small interfering RNA to endothelial cells for anti-angiogenesis tumor therapy using CD44-targeted chitosan nanoparticles for epithelial ovarian cancer

Ga Hee Kim; Ji Eun Won; Yeongseon Byeon; Min Gi Kim; Tae In Wi; Jae Myeong Lee; Yun Yong Park; Jeong Won Lee; Tae Heung Kang; In Duk Jung; Byung Cheol Shin; Hyung Jun Ahn; Young Joo Lee; Anil K. Sood; Hee Dong Han; Yeong Min Park

doi:10.1080/10717544.2018.1480672

Selective delivery of PLXDC1 small interfering RNA to endothelial cells for anti-angiogenesis tumor therapy using CD44-targeted chitosan nanoparticles for epithelial ovarian cancer

Ga Hee Kim, Ji Eun Won, Yeongseon Byeon, Min Gi Kim, Tae In Wi, Jae Myeong Lee, Yun Yong Park, Jeong Won Lee, Tae Heung Kang, In Duk Jung, Byung Cheol Shin, Hyung Jun Ahn, Young Joo Lee, Anil K. Sood, Hee Dong Han, Yeong Min Park

Gynecological Oncology & Reproductive Medicine

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

56 Scopus citations

Abstract

Angiogenesis plays an essential role in the growth and metastasis of tumor cells, and the modulation of angiogenesis can be an effective approach for cancer therapy. We focused on silencing the angiogenic gene PLXDC1 as an important factor for anti-angiogenesis tumor therapy. Herein, we developed PLXDC1 small interfering siRNA (siRNA)-incorporated chitosan nanoparticle (CH-NP/siRNA) coated with hyaluronic acid (HA) to target the CD44 receptor on tumor endothelial cells. This study aimed to improve targeted delivery and enhance therapeutic efficacy for tumor anti-angiogenesis. The HA-CH-NP/siRNA was 200 ± 10 nm in size with a zeta potential of 26.4 mV. The loading efficiency of siRNA to the HA-CH-NP/siRNA was up to 60%. The selective binding of HA-CH-NP/siRNA to CD44- positive tumor endothelial cells increased by 2.1-fold compared with that of the CD44 nontargeted CH-NP/siRNA. PLXDC1 silencing by the HA-CH-NP/siRNA significantly inhibited tumor growth in A2780 tumor-bearing mice compared with that in the control group (p<.01), and mRNA expression of PLXDC1 was significantly reduced in the HA-CH-NP/siRNA-treated group. Furthermore, treatment with HA-CH-NP/siRNA resulted in significant inhibition of cell proliferation (p<.001), reduced microvessel density (p<.001), and increased cell apoptosis (p<.001). This study demonstrates that HA-CHNP/ siRNA is a highly selective delivery platform for siRNA, and has broad potential to be used in antiangiogenesis tumor therapy.

Original language	English (US)
Pages (from-to)	1394-1402
Number of pages	9
Journal	Drug delivery
Volume	25
Issue number	1
DOIs	https://doi.org/10.1080/10717544.2018.1480672
State	Published - 2018

Keywords

Angiogenesis tumor therapy
Chitosan nanoparticles
Epithelial ovarian cancer
PLXDC1 siRNA
Targeted delivery

ASJC Scopus subject areas

Pharmaceutical Science

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10.1080/10717544.2018.1480672

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Kim, G. H., Won, J. E., Byeon, Y., Kim, M. G., Wi, T. I., Lee, J. M., Park, Y. Y., Lee, J. W., Kang, T. H., Jung, I. D., Shin, B. C., Ahn, H. J., Lee, Y. J., Sood, A. K., Han, H. D., & Park, Y. M. (2018). Selective delivery of PLXDC1 small interfering RNA to endothelial cells for anti-angiogenesis tumor therapy using CD44-targeted chitosan nanoparticles for epithelial ovarian cancer. Drug delivery, 25(1), 1394-1402. https://doi.org/10.1080/10717544.2018.1480672

Kim, GH, Won, JE, Byeon, Y, Kim, MG, Wi, TI, Lee, JM, Park, YY, Lee, JW, Kang, TH, Jung, ID, Shin, BC, Ahn, HJ, Lee, YJ, Sood, AK, Han, HD & Park, YM 2018, 'Selective delivery of PLXDC1 small interfering RNA to endothelial cells for anti-angiogenesis tumor therapy using CD44-targeted chitosan nanoparticles for epithelial ovarian cancer', Drug delivery, vol. 25, no. 1, pp. 1394-1402. https://doi.org/10.1080/10717544.2018.1480672

@article{391efd2e62c0497aad972834f9fc9be8,

title = "Selective delivery of PLXDC1 small interfering RNA to endothelial cells for anti-angiogenesis tumor therapy using CD44-targeted chitosan nanoparticles for epithelial ovarian cancer",

abstract = "Angiogenesis plays an essential role in the growth and metastasis of tumor cells, and the modulation of angiogenesis can be an effective approach for cancer therapy. We focused on silencing the angiogenic gene PLXDC1 as an important factor for anti-angiogenesis tumor therapy. Herein, we developed PLXDC1 small interfering siRNA (siRNA)-incorporated chitosan nanoparticle (CH-NP/siRNA) coated with hyaluronic acid (HA) to target the CD44 receptor on tumor endothelial cells. This study aimed to improve targeted delivery and enhance therapeutic efficacy for tumor anti-angiogenesis. The HA-CH-NP/siRNA was 200 ± 10 nm in size with a zeta potential of 26.4 mV. The loading efficiency of siRNA to the HA-CH-NP/siRNA was up to 60%. The selective binding of HA-CH-NP/siRNA to CD44- positive tumor endothelial cells increased by 2.1-fold compared with that of the CD44 nontargeted CH-NP/siRNA. PLXDC1 silencing by the HA-CH-NP/siRNA significantly inhibited tumor growth in A2780 tumor-bearing mice compared with that in the control group (p<.01), and mRNA expression of PLXDC1 was significantly reduced in the HA-CH-NP/siRNA-treated group. Furthermore, treatment with HA-CH-NP/siRNA resulted in significant inhibition of cell proliferation (p<.001), reduced microvessel density (p<.001), and increased cell apoptosis (p<.001). This study demonstrates that HA-CHNP/ siRNA is a highly selective delivery platform for siRNA, and has broad potential to be used in antiangiogenesis tumor therapy.",

keywords = "Angiogenesis tumor therapy, Chitosan nanoparticles, Epithelial ovarian cancer, PLXDC1 siRNA, Targeted delivery",

author = "Kim, {Ga Hee} and Won, {Ji Eun} and Yeongseon Byeon and Kim, {Min Gi} and Wi, {Tae In} and Lee, {Jae Myeong} and Park, {Yun Yong} and Lee, {Jeong Won} and Kang, {Tae Heung} and Jung, {In Duk} and Shin, {Byung Cheol} and Ahn, {Hyung Jun} and Lee, {Young Joo} and Sood, {Anil K.} and Han, {Hee Dong} and Park, {Yeong Min}",

note = "Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (NRF-2016R1A5A2012284, NRF-2016R1A2B2007327, and NRF-2015R1A2A2A04003620 to Y.-M.P., H.D.H., and Y.J.L.). This work was also supported by Basic Research Laboratory Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. 2013R1A4A1069575, to H.D.H., T.H.K., and I.D.J.) and a grant from the National R&D program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea (1520100 to H.D.H., H.J.A., and J.-W.L.). Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

doi = "10.1080/10717544.2018.1480672",

language = "English (US)",

volume = "25",

pages = "1394--1402",

journal = "Drug delivery",

issn = "1071-7544",

publisher = "Informa Healthcare",

number = "1",

}

TY - JOUR

T1 - Selective delivery of PLXDC1 small interfering RNA to endothelial cells for anti-angiogenesis tumor therapy using CD44-targeted chitosan nanoparticles for epithelial ovarian cancer

AU - Kim, Ga Hee

AU - Won, Ji Eun

AU - Byeon, Yeongseon

AU - Kim, Min Gi

AU - Wi, Tae In

AU - Lee, Jae Myeong

AU - Park, Yun Yong

AU - Lee, Jeong Won

AU - Kang, Tae Heung

AU - Jung, In Duk

AU - Shin, Byung Cheol

AU - Ahn, Hyung Jun

AU - Lee, Young Joo

AU - Sood, Anil K.

AU - Han, Hee Dong

AU - Park, Yeong Min

N1 - Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (NRF-2016R1A5A2012284, NRF-2016R1A2B2007327, and NRF-2015R1A2A2A04003620 to Y.-M.P., H.D.H., and Y.J.L.). This work was also supported by Basic Research Laboratory Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. 2013R1A4A1069575, to H.D.H., T.H.K., and I.D.J.) and a grant from the National R&D program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea (1520100 to H.D.H., H.J.A., and J.-W.L.). Publisher Copyright: © 2018 The Author(s).

PY - 2018

Y1 - 2018

N2 - Angiogenesis plays an essential role in the growth and metastasis of tumor cells, and the modulation of angiogenesis can be an effective approach for cancer therapy. We focused on silencing the angiogenic gene PLXDC1 as an important factor for anti-angiogenesis tumor therapy. Herein, we developed PLXDC1 small interfering siRNA (siRNA)-incorporated chitosan nanoparticle (CH-NP/siRNA) coated with hyaluronic acid (HA) to target the CD44 receptor on tumor endothelial cells. This study aimed to improve targeted delivery and enhance therapeutic efficacy for tumor anti-angiogenesis. The HA-CH-NP/siRNA was 200 ± 10 nm in size with a zeta potential of 26.4 mV. The loading efficiency of siRNA to the HA-CH-NP/siRNA was up to 60%. The selective binding of HA-CH-NP/siRNA to CD44- positive tumor endothelial cells increased by 2.1-fold compared with that of the CD44 nontargeted CH-NP/siRNA. PLXDC1 silencing by the HA-CH-NP/siRNA significantly inhibited tumor growth in A2780 tumor-bearing mice compared with that in the control group (p<.01), and mRNA expression of PLXDC1 was significantly reduced in the HA-CH-NP/siRNA-treated group. Furthermore, treatment with HA-CH-NP/siRNA resulted in significant inhibition of cell proliferation (p<.001), reduced microvessel density (p<.001), and increased cell apoptosis (p<.001). This study demonstrates that HA-CHNP/ siRNA is a highly selective delivery platform for siRNA, and has broad potential to be used in antiangiogenesis tumor therapy.

AB - Angiogenesis plays an essential role in the growth and metastasis of tumor cells, and the modulation of angiogenesis can be an effective approach for cancer therapy. We focused on silencing the angiogenic gene PLXDC1 as an important factor for anti-angiogenesis tumor therapy. Herein, we developed PLXDC1 small interfering siRNA (siRNA)-incorporated chitosan nanoparticle (CH-NP/siRNA) coated with hyaluronic acid (HA) to target the CD44 receptor on tumor endothelial cells. This study aimed to improve targeted delivery and enhance therapeutic efficacy for tumor anti-angiogenesis. The HA-CH-NP/siRNA was 200 ± 10 nm in size with a zeta potential of 26.4 mV. The loading efficiency of siRNA to the HA-CH-NP/siRNA was up to 60%. The selective binding of HA-CH-NP/siRNA to CD44- positive tumor endothelial cells increased by 2.1-fold compared with that of the CD44 nontargeted CH-NP/siRNA. PLXDC1 silencing by the HA-CH-NP/siRNA significantly inhibited tumor growth in A2780 tumor-bearing mice compared with that in the control group (p<.01), and mRNA expression of PLXDC1 was significantly reduced in the HA-CH-NP/siRNA-treated group. Furthermore, treatment with HA-CH-NP/siRNA resulted in significant inhibition of cell proliferation (p<.001), reduced microvessel density (p<.001), and increased cell apoptosis (p<.001). This study demonstrates that HA-CHNP/ siRNA is a highly selective delivery platform for siRNA, and has broad potential to be used in antiangiogenesis tumor therapy.

KW - Angiogenesis tumor therapy

KW - Chitosan nanoparticles

KW - Epithelial ovarian cancer

KW - PLXDC1 siRNA

KW - Targeted delivery

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VL - 25

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ER -

Selective delivery of PLXDC1 small interfering RNA to endothelial cells for anti-angiogenesis tumor therapy using CD44-targeted chitosan nanoparticles for epithelial ovarian cancer

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Keywords

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