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Monitoring the in vivo siRNA release from lipid nanoparticles based on the fluorescence resonance energy transfer principle

摘要The siRNA-loaded lipid nanoparticles have attracted much attention due to its significant gene silencing effect and successful marketization.However,the in vivo distribution and release of siRNA still cannot be effectively monitored.In this study,based on the fluorescence resonance energy transfer(FRET)principle,a fluorescence dye Cy5-modified survivin siRNA was conjugated to nanogolds(Au-DR-siRNA),which were then wrapped with lipid nanoparticles(LNPs)for monitoring the release behaviour of siRNA in vivo.The results showed that once Au-DR-siRNA was released from the LNPs and cleaved by the Dicer enzyme to produce free siRNA in cells,the fluorescence of Cy5 would change from quenched state to activated state,showing the location and time of siRNA release.Besides,the LNPs showed a significant antitumor effect by silencing the survivin gene and a CT imaging function superior to iohexol by nanogolds.Therefore,this work provided not only an effective method for monitoring the pharmacokinetic behaviour of LNP-based siRNA,but also a siRNA delivery system for treating and diagnosing tumors.

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作者 Lei Sun [1] Jinfang Zhang [1] Jing-e Zhou [1] Jing Wang [1] Zhehao Wang [1] Shenggen Luo [1] Yeying Wang [1] Shulei Zhu [2] Fan Yang [2] Jie Tang [2] Wei Lu [2] Yiting Wang [1] Lei Yu [1] Zhiqiang Yan [2] 学术成果认领
作者单位 Institute of Biomedical Engineering and Technology,Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development,School of Chemistry and Molecular Engineering,East China Normal University,Shanghai 200062,China [1] Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development,School of Chemistry and Molecular Engineering,East China Normal University,Shanghai 200062,China [2]
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DOI 10.1016/j.ajps.2022.11.003
发布时间 2023-11-17(万方平台首次上网日期,不代表论文的发表时间)
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