Intravenous transferrin, RGD peptide and dual-targeted nanoparticles enhance anti-VEGF intraceptor gene delivery to laser-induced CNV.
Intravenous transferrin, RGD peptide and dual-targeted nanoparticles enhance anti-VEGF intraceptor gene delivery to laser-induced CNV.
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脉络膜新生血管 (CNV) 会导致年龄相关性黄斑变性 (AMD) 视力丧失，这是 50 岁以上成年人失明的主要原因。在这项研究中，我们开发了静脉注射、纳米颗粒、靶向非病毒视网膜基因递送系统，用于治疗 CNV。使用 532 nm 激光在挪威棕色大鼠中诱导 CNV。我们设计了转铁蛋白、精氨酸-甘氨酸-天冬氨酸 (RGD) 肽或双功能化聚（丙交酯-乙交酯）纳米颗粒，以将抗血管内皮生长因子 (VEGF) 内受体质粒靶向递送至 CNV 病变。抗 VEGF 内受体是唯一的细胞内作用 VEGF 抑制方式。研究结果表明，纳米颗粒可以有针对性地输送到新生血管眼，但静脉注射时不能输送到对照眼。与非功能化纳米颗粒相比，用转铁蛋白、线性RGD肽或两者对纳米颗粒表面进行功能化可增加纳米颗粒的视网膜递送，并随后增加视网膜血管内皮细胞、光感受器外节和视网膜色素上皮细胞中的内受体基因表达。最重要的是，与用载体或非功能化纳米颗粒治疗的大鼠相比，用功能化纳米颗粒治疗的大鼠的 CNV 面积明显更小。因此，表面功能化纳米粒子允许通过静脉注射将靶向基因递送至新生血管眼，并抑制啮齿动物模型中激光诱导的 CNV 的进展。
Choroidal neovascularization (CNV) leads to loss of vision in age-related macular degeneration (AMD), the leading cause of blindness in adult population over 50 years old. In this study, we developed intravenously administered, nanoparticulate, targeted nonviral retinal gene delivery systems for the management of CNV. CNV was induced in Brown Norway rats using a 532 nm laser. We engineered transferrin, arginine–glycine–aspartic acid (RGD) peptide or dual-functionalized poly-(lactide-co-glycolide) nanoparticles to target delivery of anti-vascular endothelial growth factor (VEGF) intraceptor plasmid to CNV lesions. Anti-VEGF intraceptor is the only intracellularly acting VEGF inhibitory modality. The results of the study show that nanoparticles allow targeted delivery to the neovascular eye but not the control eye on intravenous administration. Functionalizing the nanoparticle surface with transferrin, a linear RGD peptide or both increased the retinal delivery of nanoparticles and subsequently the intraceptor gene expression in retinal vascular endothelial cells, photoreceptor outer segments and retinal pigment epithelial cells when compared to nonfunctionalized nanoparticles. Most significantly, the CNV areas were significantly smaller in rats treated with functionalized nanoparticles as compared to the ones treated with vehicle or nonfunctionalized nanoparticles. Thus, surface-functionalized nanoparticles allow targeted gene delivery to the neovascular eye on intravenous administration and inhibit the progression of laser-induced CNV in a rodent model.
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影响因子：
10.8
作者：
Kocbek, Petra;Obermajer, Natasa;Kristl, Julijana
通讯作者：
Kristl, Julijana
DOI：
10.1073/pnas.93.18.9764
发表时间：
1996-09-03
影响因子：
11.1
作者：
Friedlander, M;Theesfeld, CL;Cheresh, DA
通讯作者：
Cheresh, DA
DOI：
10.1016/s0304-4165(01)00132-5
发表时间：
2001-05-03
影响因子：
3
作者：
Furumoto, K;Ogawara, K;Kimura, T
通讯作者：
Kimura, T
影响因子：
64.8
作者：
Gerber, HP;Malik, AK;Ferrara, N
通讯作者：
Ferrara, N
影响因子：
4.4
作者：
Bourges, JL;Gautier, SE;Behar-Cohen, FF
通讯作者：
Behar-Cohen, FF