Non-Viral Gene Therapy in Trabecular Meshwork Cells to Prevent Fibrosis in Minimally Invasive Glaucoma Surgery.
Non-Viral Gene Therapy in Trabecular Meshwork Cells to Prevent Fibrosis in Minimally Invasive Glaucoma Surgery.
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DOI：
10.3390/pharmaceutics14112472
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发表时间：
2022-11-16
期刊：
影响因子：
5.4
通讯作者：
Yu-Wai-Man C
中科院分区：
文献类型：
--
作者：
Luo J;Tan G;Thong KX;Kafetzis KN;Vallabh N;Sheridan CM;Sato Y;Harashima H;Tagalakis AD;Yu-Wai-Man C
微创青光眼手术（MIGS）失败的主要原因是调节房水流出的小梁网（TM）中的纤维化，并且没有抗纤维化药物可用于MIGS中的眼内使用。肌心蛋白相关转录因子/血清反应因子（MRTF/SRF）通路是一个很有前途的抗纤维化靶点。本研究旨在利用新型脂质纳米颗粒（LNP）将MRTF-B siRNA递送到人TM细胞中，并将其效果与在人结膜成纤维细胞（FF）中观察到的效果进行比较。制备两种具有和不具有靶向肽c的LNP制剂，并且siRNA浓度为50 nM。我们检查了LNP的生物物理性质和包封效率，并评估了MRTF-B沉默对细胞活力、关键纤维化基因表达和细胞收缩性的影响。两种LNP制剂均有效沉默MRTF-B基因，并且在TM和FF细胞中无细胞毒性。c的存在使得LNP更小且更具阳离子性，但对包封效率没有显著影响。TM和FF细胞在用MRTF-B siRNA LNP转染后也显示出显著降低的收缩性。在TM细胞中，与不含c的LNP相比，含c的LNP实现了更大的收缩性降低。总之，我们证明了新型CL 4 H6-LNP能够安全有效地将MRTF-B siRNA递送到人TM细胞中。LNP可以作为一种有前途的非病毒基因治疗，以防止MIGS中的纤维化。
The primary cause of failure for minimally invasive glaucoma surgery (MIGS) is fibrosis in the trabecular meshwork (TM) that regulates the outflow of aqueous humour, and no anti-fibrotic drug is available for intraocular use in MIGS. The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway is a promising anti-fibrotic target. This study aims to utilise a novel lipid nanoparticle (LNP) to deliver MRTF-B siRNA into human TM cells and to compare its effects with those observed in human conjunctival fibroblasts (FF). Two LNP formulations were prepared with and without the targeting peptide c, and with an siRNA concentration of 50 nM. We examined the biophysical properties and encapsulation efficiencies of the LNPs, and evaluated the effects of MRTF-B silencing on cell viability, key fibrotic genes expression and cell contractility. Both LNP formulations efficiently silenced MRTF-B gene and were non-cytotoxic in TM and FF cells. The presence of c made the LNPs smaller and more cationic, but had no significant effect on encapsulation efficiency. Both TM and FF cells also showed significantly reduced contractibility after transfection with MRTF-B siRNA LNPs. In TM cells, LNPs with c achieved a greater decrease in contractility compared to LNPs without c. In conclusion, we demonstrate that the novel CL4H6-LNPs are able to safely and effectively deliver MRTF-B siRNA into human TM cells. LNPs can serve as a promising non-viral gene therapy to prevent fibrosis in MIGS.
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影响因子：
3.4
作者：
Keller, Kate E.;Aga, Mini;Bradley, John M.;Kelley, Mary J.;Acott, Ted S.
通讯作者：
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DOI：
10.1016/j.nano.2016.12.014
发表时间：
2017-05-01
影响因子：
5.4
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.1306529110
发表时间：
2013-08-06
影响因子：
11.1
作者：
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通讯作者：
Anderson, Daniel G.
DOI：
10.1007/978-1-60327-198-1_6
发表时间：
2011-01-01
期刊：
CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY
影响因子：
--
作者：
Clogston, Jeffrey D.;Patri, Anil K.
通讯作者：
Patri, Anil K.