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
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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.
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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。
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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.
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