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Trophoblast-Targeted Nanomedicine Modulates Placental sFLT1 for Preeclampsia Treatment
The overexpressed soluble fms-like tyrosine kinase 1 (sFLT-1) in placenta is considered to be a potential therapeutic target for preeclampsia (PE). How to achieve efficient intervention of sFLT1 expression in the placenta is an urgent problem to be solved. PEG-PLA nanoparticle generated by double-em...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026029/ https://www.ncbi.nlm.nih.gov/pubmed/32117942 http://dx.doi.org/10.3389/fbioe.2020.00064 |
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author | Li, Lei Yang, Huijun Chen, Pengzheng Xin, Tao Zhou, Qian Wei, Dan Zhang, Yanan Wang, Shan |
author_facet | Li, Lei Yang, Huijun Chen, Pengzheng Xin, Tao Zhou, Qian Wei, Dan Zhang, Yanan Wang, Shan |
author_sort | Li, Lei |
collection | PubMed |
description | The overexpressed soluble fms-like tyrosine kinase 1 (sFLT-1) in placenta is considered to be a potential therapeutic target for preeclampsia (PE). How to achieve efficient intervention of sFLT1 expression in the placenta is an urgent problem to be solved. PEG-PLA nanoparticle generated by double-emulsion methods is a novel siRNA delivery system. Synthetic placental CSA binding peptide (P-CSA-BP) is effective for targeting lipid-polymer nanoparticle to the placenta. We conjugated P-CSA-BP to the surface of PEG-PLA nanoparticle to create a novel placenta specific sFLT1 siRNA delivery system for the therapy of PE. Nanoparticles were synthesized using double emulsion method and characterized by dynamic light scattering and transmission electron microscopy (TEM). RT-PCR was employed to evaluate mRNA level and protein level was analyzed by ELISA kit. The tissue distribution of nanoparticles was observed through ex vivo images. The concentrations of nanoparticles in organs were measured using high-performance liquid chromatography. T-NP(si)(sFLT1) had higher efficiency than NP(si)(sFLT1) in accumulating in HTR-8/SVneo cells and significantly decreased the expression of sFLT1. Intravenously administered T-NP(si)(sFLT1) specifically accumulated in placentas of mice. sFLT1 mRNA level in placenta and protein level in serum were declined by T-NP(si)(sFLT1). T-NP(si)(sFLT1) shown no obvious toxic effect on both mother and fetus. The utility of T-NPsisFLT1 nanoparticles as a sFLT1 siRNA placenta specific delivery system significantly silenced sFLT1 in mice and is safe for both mother and fetus. This nanoparticle is a novel potential therapeutic strategy for PE. |
format | Online Article Text |
id | pubmed-7026029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70260292020-02-28 Trophoblast-Targeted Nanomedicine Modulates Placental sFLT1 for Preeclampsia Treatment Li, Lei Yang, Huijun Chen, Pengzheng Xin, Tao Zhou, Qian Wei, Dan Zhang, Yanan Wang, Shan Front Bioeng Biotechnol Bioengineering and Biotechnology The overexpressed soluble fms-like tyrosine kinase 1 (sFLT-1) in placenta is considered to be a potential therapeutic target for preeclampsia (PE). How to achieve efficient intervention of sFLT1 expression in the placenta is an urgent problem to be solved. PEG-PLA nanoparticle generated by double-emulsion methods is a novel siRNA delivery system. Synthetic placental CSA binding peptide (P-CSA-BP) is effective for targeting lipid-polymer nanoparticle to the placenta. We conjugated P-CSA-BP to the surface of PEG-PLA nanoparticle to create a novel placenta specific sFLT1 siRNA delivery system for the therapy of PE. Nanoparticles were synthesized using double emulsion method and characterized by dynamic light scattering and transmission electron microscopy (TEM). RT-PCR was employed to evaluate mRNA level and protein level was analyzed by ELISA kit. The tissue distribution of nanoparticles was observed through ex vivo images. The concentrations of nanoparticles in organs were measured using high-performance liquid chromatography. T-NP(si)(sFLT1) had higher efficiency than NP(si)(sFLT1) in accumulating in HTR-8/SVneo cells and significantly decreased the expression of sFLT1. Intravenously administered T-NP(si)(sFLT1) specifically accumulated in placentas of mice. sFLT1 mRNA level in placenta and protein level in serum were declined by T-NP(si)(sFLT1). T-NP(si)(sFLT1) shown no obvious toxic effect on both mother and fetus. The utility of T-NPsisFLT1 nanoparticles as a sFLT1 siRNA placenta specific delivery system significantly silenced sFLT1 in mice and is safe for both mother and fetus. This nanoparticle is a novel potential therapeutic strategy for PE. Frontiers Media S.A. 2020-02-11 /pmc/articles/PMC7026029/ /pubmed/32117942 http://dx.doi.org/10.3389/fbioe.2020.00064 Text en Copyright © 2020 Li, Yang, Chen, Xin, Zhou, Wei, Zhang and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioengineering and Biotechnology Li, Lei Yang, Huijun Chen, Pengzheng Xin, Tao Zhou, Qian Wei, Dan Zhang, Yanan Wang, Shan Trophoblast-Targeted Nanomedicine Modulates Placental sFLT1 for Preeclampsia Treatment |
title | Trophoblast-Targeted Nanomedicine Modulates Placental sFLT1 for Preeclampsia Treatment |
title_full | Trophoblast-Targeted Nanomedicine Modulates Placental sFLT1 for Preeclampsia Treatment |
title_fullStr | Trophoblast-Targeted Nanomedicine Modulates Placental sFLT1 for Preeclampsia Treatment |
title_full_unstemmed | Trophoblast-Targeted Nanomedicine Modulates Placental sFLT1 for Preeclampsia Treatment |
title_short | Trophoblast-Targeted Nanomedicine Modulates Placental sFLT1 for Preeclampsia Treatment |
title_sort | trophoblast-targeted nanomedicine modulates placental sflt1 for preeclampsia treatment |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026029/ https://www.ncbi.nlm.nih.gov/pubmed/32117942 http://dx.doi.org/10.3389/fbioe.2020.00064 |
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