Ocular delivery of compacted DNA-nanoparticles does not elicit toxicity in the mouse retina.
Ocular delivery of compacted DNA-nanoparticles does not elicit toxicity in the mouse retina.
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DOI：
10.1371/journal.pone.0007410
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发表时间：
2009-10-12
期刊：
影响因子：
3.7
通讯作者：
Naash MI
中科院分区：
文献类型：
--
作者：
Ding XQ;Quiambao AB;Fitzgerald JB;Cooper MJ;Conley SM;Naash MI
聚乙二醇取代的赖氨酸肽 (CK30PEG) 压缩 DNA 纳米颗粒的视网膜下递送可在视网膜细胞中实现有效的基因表达。这项工作评估了压缩 DNA 纳米颗粒的眼部安全性。将含有 EGFP 表达质粒的 CK30PEG 压实纳米颗粒注射到成年小鼠视网膜下（1 µl，浓度为 0.3、1.0 和 3.0 µg/µl）。注射后 1、2、4 和 7 天检查视网膜是否有炎症迹象。视网膜中未检测到多形核中性粒细胞或淋巴细胞浸润。此外，在注射的眼睛中未检测到巨噬细胞标记物F4/80或骨髓标记物髓过氧化物酶的升高。在注射纳米颗粒或盐水后 1 天，趋化因子 KC mRNA 增加了 3-4 倍，但在注射后 2 天恢复到对照水平。在这些小鼠中没有观察到 KC 蛋白升高。对于注射纳米颗粒和注射盐水的眼睛，单核细胞趋化蛋白-1 在注射后 1 天增加了 3-4 倍，但在 2 天时也恢复到对照水平。未检测到肿瘤坏死因子 α mRNA 或蛋白质升高。这些研究没有显示与视网膜下注射压缩 DNA 纳米颗粒相关的局部炎症反应的迹象，表明视网膜可能是临床纳米颗粒干预的合适目标。
Subretinal delivery of polyethylene glycol-substituted lysine peptide (CK30PEG)-compacted DNA nanoparticles results in efficient gene expression in retinal cells. This work evaluates the ocular safety of compacted DNA nanoparticles. CK30PEG-compacted nanoparticles containing an EGFP expression plasmid were subretinally injected in adult mice (1 µl at 0.3, 1.0 and 3.0 µg/µl). Retinas were examined for signs of inflammation at 1, 2, 4 and 7 days post-injection. Neither infiltration of polymorphonuclear neutrophils or lymphocytes was detected in retinas. In addition, elevation of macrophage marker F4/80 or myeloid marker myeloperoxidase was not detected in the injected eyes. The chemokine KC mRNA increased 3–4 fold in eyes injected with either nanoparticles or saline at 1 day post-injection, but returned to control levels at 2 days post-injection. No elevation of KC protein was observed in these mice. The monocyte chemotactic protein-1, increased 3–4 fold at 1 day post-injection for both nanoparticle and saline injected eyes, but also returned to control levels at 2 days. No elevations of tumor necrosis factor alpha mRNA or protein were detected. These investigations show no signs of local inflammatory responses associated with subretinal injection of compacted DNA nanoparticles, indicating that the retina may be a suitable target for clinical nanoparticle-based interventions.
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影响因子：
17.1
作者：
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用压实的DNA纳米颗粒有效的非病毒眼基因转移。
影响因子：
3.7
作者：
Farjo, Rafal;Skaggs, Jeff;Quiambao, Alexander B.;Cooper, Mark J.;Naash, Muna I.
通讯作者：
Naash, Muna I.