Preparation of nanobubbles carrying androgen receptor siRNA and their inhibitory effects on androgen-independent prostate cancer when combined with ultrasonic irradiation.
<h4>Objective</h4>The objective of this study was to investigate nanobubbles carrying androgen receptor (AR) siRNA and their in vitro and in vivo anti-tumor effects, when combined with ultrasonic irradiation, on androgen-independent prostate cancer (AIPC).<h4>Materials and methods&...
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Format: | Article |
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Public Library of Science (PLoS)
2014-01-01
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Series: | PLoS ONE |
Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096586&type=printable |
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author | Luofu Wang Miao Zhang Kaibin Tan Yanli Guo Haipeng Tong Xiaozhou Fan Kejing Fang Rui Li |
author_facet | Luofu Wang Miao Zhang Kaibin Tan Yanli Guo Haipeng Tong Xiaozhou Fan Kejing Fang Rui Li |
author_sort | Luofu Wang |
collection | DOAJ |
description | <h4>Objective</h4>The objective of this study was to investigate nanobubbles carrying androgen receptor (AR) siRNA and their in vitro and in vivo anti-tumor effects, when combined with ultrasonic irradiation, on androgen-independent prostate cancer (AIPC).<h4>Materials and methods</h4>Nanobubbles carrying AR siRNA were prepared using poly-L-lysine and electrostatic adsorption methods. Using C4-2 cell activity as a testing index, the optimal irradiation parameters (including the nanobubble number/cell number ratio, mechanical index [MI], and irradiation time) were determined and used for transfection of three human prostate cancer cell lines (C4-2, LNCaP, and PC-3 cells). The AR expression levels were investigated with RT-PCR and Western blot analysis. Additionally, the effects of the nanobubbles and control microbubbles named SonoVue were assessed via imaging in a C4-2 xenograft model. Finally, the growth and AR expression of seven groups of tumor tissues were assessed using the C4-2 xenograft mouse model.<h4>Results</h4>The nanobubbles had an average diameter of 609.5±15.6 nm and could effectively bind to AR siRNA. Under the optimized conditions of a nanobubble number/cell number ratio of 100∶1, an MI of 1.2, and an irradiation time of 2 min, the highest transfection rates in C4-2, LNCaP, and PC-3 cells were 67.4%, 74.0%, and 63.96%, respectively. In the C4-2 and LNCaP cells, treatment with these binding nanobubbles plus ultrasonic irradiation significantly inhibited cell growth and resulted in the suppression of AR mRNA and protein expression. Additionally, contrast-enhanced ultrasound showed that the nanobubbles achieved stronger signals than the SonoVue control in the central hypovascular area of the tumors. Finally, the anti-tumor effect of these nanobubbles plus ultrasonic irradiation was most significant in the xenograft tumor model compared with the other groups.<h4>Conclusion</h4>Nanobubbles carrying AR siRNA could be potentially used as gene vectors in combination with ultrasonic irradiation for the treatment of AIPC. |
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spelling | doaj.art-38bbbec8b7e74f2c855afdcfb20b1d6c2025-02-22T05:32:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9658610.1371/journal.pone.0096586Preparation of nanobubbles carrying androgen receptor siRNA and their inhibitory effects on androgen-independent prostate cancer when combined with ultrasonic irradiation.Luofu WangMiao ZhangKaibin TanYanli GuoHaipeng TongXiaozhou FanKejing FangRui Li<h4>Objective</h4>The objective of this study was to investigate nanobubbles carrying androgen receptor (AR) siRNA and their in vitro and in vivo anti-tumor effects, when combined with ultrasonic irradiation, on androgen-independent prostate cancer (AIPC).<h4>Materials and methods</h4>Nanobubbles carrying AR siRNA were prepared using poly-L-lysine and electrostatic adsorption methods. Using C4-2 cell activity as a testing index, the optimal irradiation parameters (including the nanobubble number/cell number ratio, mechanical index [MI], and irradiation time) were determined and used for transfection of three human prostate cancer cell lines (C4-2, LNCaP, and PC-3 cells). The AR expression levels were investigated with RT-PCR and Western blot analysis. Additionally, the effects of the nanobubbles and control microbubbles named SonoVue were assessed via imaging in a C4-2 xenograft model. Finally, the growth and AR expression of seven groups of tumor tissues were assessed using the C4-2 xenograft mouse model.<h4>Results</h4>The nanobubbles had an average diameter of 609.5±15.6 nm and could effectively bind to AR siRNA. Under the optimized conditions of a nanobubble number/cell number ratio of 100∶1, an MI of 1.2, and an irradiation time of 2 min, the highest transfection rates in C4-2, LNCaP, and PC-3 cells were 67.4%, 74.0%, and 63.96%, respectively. In the C4-2 and LNCaP cells, treatment with these binding nanobubbles plus ultrasonic irradiation significantly inhibited cell growth and resulted in the suppression of AR mRNA and protein expression. Additionally, contrast-enhanced ultrasound showed that the nanobubbles achieved stronger signals than the SonoVue control in the central hypovascular area of the tumors. Finally, the anti-tumor effect of these nanobubbles plus ultrasonic irradiation was most significant in the xenograft tumor model compared with the other groups.<h4>Conclusion</h4>Nanobubbles carrying AR siRNA could be potentially used as gene vectors in combination with ultrasonic irradiation for the treatment of AIPC.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096586&type=printable |
spellingShingle | Luofu Wang Miao Zhang Kaibin Tan Yanli Guo Haipeng Tong Xiaozhou Fan Kejing Fang Rui Li Preparation of nanobubbles carrying androgen receptor siRNA and their inhibitory effects on androgen-independent prostate cancer when combined with ultrasonic irradiation. PLoS ONE |
title | Preparation of nanobubbles carrying androgen receptor siRNA and their inhibitory effects on androgen-independent prostate cancer when combined with ultrasonic irradiation. |
title_full | Preparation of nanobubbles carrying androgen receptor siRNA and their inhibitory effects on androgen-independent prostate cancer when combined with ultrasonic irradiation. |
title_fullStr | Preparation of nanobubbles carrying androgen receptor siRNA and their inhibitory effects on androgen-independent prostate cancer when combined with ultrasonic irradiation. |
title_full_unstemmed | Preparation of nanobubbles carrying androgen receptor siRNA and their inhibitory effects on androgen-independent prostate cancer when combined with ultrasonic irradiation. |
title_short | Preparation of nanobubbles carrying androgen receptor siRNA and their inhibitory effects on androgen-independent prostate cancer when combined with ultrasonic irradiation. |
title_sort | preparation of nanobubbles carrying androgen receptor sirna and their inhibitory effects on androgen independent prostate cancer when combined with ultrasonic irradiation |
url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096586&type=printable |
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