Sustained intra-cellular siRNA release from Poly(hypenCapswithspaceRetainColl1rginine) multilayered nanoparticles for prolonged gene silencing.

IF 5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Expert Opinion on Drug Delivery Pub Date : 2024-09-18 DOI:10.1080/17425247.2024.2405206
Alice Ng Jie Ying,Yang Fei Tan,Yee Shan Wong,Subbu Venkatraman
{"title":"Sustained intra-cellular siRNA release from Poly(hypenCapswithspaceRetainColl1rginine) multilayered nanoparticles for prolonged gene silencing.","authors":"Alice Ng Jie Ying,Yang Fei Tan,Yee Shan Wong,Subbu Venkatraman","doi":"10.1080/17425247.2024.2405206","DOIUrl":null,"url":null,"abstract":"BACKGROUND\r\nSustained siRNA release from nanocarriers is difficult to achieve inside the cell after entry: typically, all nanocarriers exhibit burst release of the cargo into the cytoplasm.\r\n\r\nRESEARCH DESIGN AND METHODS\r\nLayer by layer (LbL) nanoparticles (NPs) can be constructed so that they escape endosomes intact, and subsequently exhibit sustained release of the cargo. Our work quantifies intra-cellular siRNA release from multilayered NPs, evaluates mechanism behind the sustained release, and optimizes the duration of release.\r\n\r\nRESULTS\r\nIntra-cellular studies showed that nanoparticles developed with 4 layers of polyL-arginine, alternated with 3 layers of siRNA layers was able to elicit effective and prolonged SPARC knockdown activity over 21 days with a single dose treatment. For the first time, we have quantified the amounts of released siRNA in the cytoplasm and the amount of siRNA remaining inside the nanoparticles at each timepoint. Furthermore, we have correlated the amount of released siRNA within cells by LbL NPs to the cellular knockdown efficiency of multilayered delivery system.\r\n\r\nCONCLUSIONS\r\nThis methodology may provide an excellent screening tool for assessing the duration of gene silencing by various nanocarrier formulations.","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":"77 1","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Drug Delivery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17425247.2024.2405206","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

BACKGROUND Sustained siRNA release from nanocarriers is difficult to achieve inside the cell after entry: typically, all nanocarriers exhibit burst release of the cargo into the cytoplasm. RESEARCH DESIGN AND METHODS Layer by layer (LbL) nanoparticles (NPs) can be constructed so that they escape endosomes intact, and subsequently exhibit sustained release of the cargo. Our work quantifies intra-cellular siRNA release from multilayered NPs, evaluates mechanism behind the sustained release, and optimizes the duration of release. RESULTS Intra-cellular studies showed that nanoparticles developed with 4 layers of polyL-arginine, alternated with 3 layers of siRNA layers was able to elicit effective and prolonged SPARC knockdown activity over 21 days with a single dose treatment. For the first time, we have quantified the amounts of released siRNA in the cytoplasm and the amount of siRNA remaining inside the nanoparticles at each timepoint. Furthermore, we have correlated the amount of released siRNA within cells by LbL NPs to the cellular knockdown efficiency of multilayered delivery system. CONCLUSIONS This methodology may provide an excellent screening tool for assessing the duration of gene silencing by various nanocarrier formulations.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
从聚(带空间保留环)多层纳米粒子中持续释放细胞内 siRNA 以延长基因沉默时间
背景纳米载体进入细胞后很难在细胞内实现 siRNA 的持续释放:通常,所有纳米载体都表现出货物向细胞质的猝发释放。结果细胞内研究表明,由 4 层聚精氨酸层和 3 层 siRNA 层交替组成的纳米颗粒能在 21 天的单剂量治疗中有效并持久地敲除 SPARC。我们首次量化了细胞质中释放的 siRNA 量和纳米颗粒中残留的 siRNA 量。此外,我们还将 LbL NPs 在细胞内释放的 siRNA 量与多层递送系统的细胞敲除效率联系起来。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
11.10
自引率
3.00%
发文量
104
审稿时长
3 months
期刊介绍: Expert Opinion on Drug Delivery (ISSN 1742-5247 [print], 1744-7593 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles covering all aspects of drug delivery research, from initial concept to potential therapeutic application and final relevance in clinical use. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.
期刊最新文献
Alternative routes for parenteral nucleic acid delivery and related hurdles: highlights in RNA delivery Sustained intra-cellular siRNA release from Poly(hypenCapswithspaceRetainColl1rginine) multilayered nanoparticles for prolonged gene silencing. Development of in vitro biopharmaceutics tools for predicting the bioavailability of subcutaneously injected monoclonal antibodies and oligonucleotides 3D printed personalized therapies for pediatric patients affected by adrenal insufficiency Redefining drug therapy: innovative approaches using catalytic compartments.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1