Effective treatment of retinal neovascular leakage with fusogenic porous silicon nanoparticles delivering VEGF-siRNA

使用融合多孔硅纳米粒子递送 VEGF-siRNA 有效治疗视网膜新生血管渗漏

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作者:Joel F Grondek, Kristyn Huffman, Ella Jiyoon Lee, Melina Cavichini, Alexandra Warter, Fritz Gerald P Kalaw, Anna Heinke, Ruhan Fan, Lingyun Cheng, Michael J Sailor, William R Freeman

Aim

To evaluate an intravitreally injected nanoparticle platform designed to deliver VEGF-A siRNA to inhibit retinal neovascular leakage as a new treatment for proliferative diabetic retinopathy and diabetic macular edema. Materials &

Conclusion

Fusogenic lipid-coated porous silicon nanoparticles siRNA delivery provides persistent knockdown of VEGF-A and reduced leakage in a rabbit model of retinal neovascularization as a potential new intraocular therapeutic.

Methods

Fusogenic lipid-coated porous silicon nanoparticles loaded with VEGF-A siRNA, and pendant neovascular integrin-homing iRGD, were evaluated for efficacy by intravitreal injection in a rabbit model of retinal neovascularization.

Results

For 12 weeks post-treatment, a reduction in vascular leakage was observed for treated diseased eyes versus control eyes (p = 0.0137), with a corresponding reduction in vitreous VEGF-A.

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