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Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer

BACKGROUND: For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically. RESULTS: The results indicated that Fe-doped...

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Autores principales: Liu, Jianye, Zhang, Yi, Zeng, Hongliang, Wang, Long, Zhang, Qun, Wu, Pei, Liu, Xiaoming, Xie, Hongyi, Xiang, Wei, Liu, Biao, Liu, Jiahao, Liu, Xuewen, Xie, Jianfei, Tang, Jin, Long, Zhi, He, Leye, Xiao, Mengqing, Xiang, Liang, Cao, Ke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220725/
https://www.ncbi.nlm.nih.gov/pubmed/34162370
http://dx.doi.org/10.1186/s12951-021-00935-z
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author Liu, Jianye
Zhang, Yi
Zeng, Hongliang
Wang, Long
Zhang, Qun
Wu, Pei
Liu, Xiaoming
Xie, Hongyi
Xiang, Wei
Liu, Biao
Liu, Jiahao
Liu, Xuewen
Xie, Jianfei
Tang, Jin
Long, Zhi
He, Leye
Xiao, Mengqing
Xiang, Liang
Cao, Ke
author_facet Liu, Jianye
Zhang, Yi
Zeng, Hongliang
Wang, Long
Zhang, Qun
Wu, Pei
Liu, Xiaoming
Xie, Hongyi
Xiang, Wei
Liu, Biao
Liu, Jiahao
Liu, Xuewen
Xie, Jianfei
Tang, Jin
Long, Zhi
He, Leye
Xiao, Mengqing
Xiang, Liang
Cao, Ke
author_sort Liu, Jianye
collection PubMed
description BACKGROUND: For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically. RESULTS: The results indicated that Fe-doped chrysotile nanotubes (FeSiNTs) with a relatively uniform outer diameter (15–25 nm) and inner diameter (7–8 nm), and a length of several hundred nanometers, which delivered an siRNA against the SPAG5 oncogene (siSPAG5) efficiently. The nanomaterials were designed to prolong the half-life of siSPAG5 in blood, increase tumor cell-specific uptake, and maximize the efficiency of SPAG5 silencing. In vitro, FeSiNTs carrying siSPAG5 inhibited the growth, migration, and invasion of bladder cancer cells. In vivo, the FeSiNTs inhibited growth and metastasis in three models of bladder tumors (a tail vein injection lung metastatic model, an in-situ bladder cancer model, and a subcutaneous model) with no obvious toxicities. Mechanistically, we showed that FeSiNTs/siSPAG5 repressed PI3K/AKT/mTOR signaling, which suppressed the growth and progression of tumor cells. CONCLUSIONS: The results highlight that FeSiNTs/siSPAG5 caused no activation of the innate immune response nor any systemic toxicity, indicating the possible therapeutic utility of FeSiNTs/siSPAG5 to deliver siSPAG5 to treat bladder cancer. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00935-z.
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spelling pubmed-82207252021-06-23 Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer Liu, Jianye Zhang, Yi Zeng, Hongliang Wang, Long Zhang, Qun Wu, Pei Liu, Xiaoming Xie, Hongyi Xiang, Wei Liu, Biao Liu, Jiahao Liu, Xuewen Xie, Jianfei Tang, Jin Long, Zhi He, Leye Xiao, Mengqing Xiang, Liang Cao, Ke J Nanobiotechnology Research BACKGROUND: For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically. RESULTS: The results indicated that Fe-doped chrysotile nanotubes (FeSiNTs) with a relatively uniform outer diameter (15–25 nm) and inner diameter (7–8 nm), and a length of several hundred nanometers, which delivered an siRNA against the SPAG5 oncogene (siSPAG5) efficiently. The nanomaterials were designed to prolong the half-life of siSPAG5 in blood, increase tumor cell-specific uptake, and maximize the efficiency of SPAG5 silencing. In vitro, FeSiNTs carrying siSPAG5 inhibited the growth, migration, and invasion of bladder cancer cells. In vivo, the FeSiNTs inhibited growth and metastasis in three models of bladder tumors (a tail vein injection lung metastatic model, an in-situ bladder cancer model, and a subcutaneous model) with no obvious toxicities. Mechanistically, we showed that FeSiNTs/siSPAG5 repressed PI3K/AKT/mTOR signaling, which suppressed the growth and progression of tumor cells. CONCLUSIONS: The results highlight that FeSiNTs/siSPAG5 caused no activation of the innate immune response nor any systemic toxicity, indicating the possible therapeutic utility of FeSiNTs/siSPAG5 to deliver siSPAG5 to treat bladder cancer. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00935-z. BioMed Central 2021-06-23 /pmc/articles/PMC8220725/ /pubmed/34162370 http://dx.doi.org/10.1186/s12951-021-00935-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Jianye
Zhang, Yi
Zeng, Hongliang
Wang, Long
Zhang, Qun
Wu, Pei
Liu, Xiaoming
Xie, Hongyi
Xiang, Wei
Liu, Biao
Liu, Jiahao
Liu, Xuewen
Xie, Jianfei
Tang, Jin
Long, Zhi
He, Leye
Xiao, Mengqing
Xiang, Liang
Cao, Ke
Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer
title Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer
title_full Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer
title_fullStr Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer
title_full_unstemmed Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer
title_short Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer
title_sort fe-doped chrysotile nanotubes containing sirnas to silence spag5 to treat bladder cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220725/
https://www.ncbi.nlm.nih.gov/pubmed/34162370
http://dx.doi.org/10.1186/s12951-021-00935-z
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