Targeted Delivery of FLT-Morpholino Using Cyclic RGD Peptide
Targeted Delivery of FLT-Morpholino Using Cyclic RGD Peptide
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DOI：
10.1167/tvst.6.3.9
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发表时间：
2017-05-01
影响因子：
3
通讯作者：
Ambati，Balamurali K.
中科院分区：
文献类型：
--
作者：
Uehara，Hironori;Muddana，Santosh Kumar;Ambati，Balamurali K.
Purpose: We previously showed that intravitreal injection of the sFLT morpholino-oligomer (FLT-MO) suppresses laser-induced choroidal neovascularization (CNV) in mice by decreasing the membrane bound form of Flt-1 while increasing the soluble form of Flt-1 via alternative splicing shift. In this study, we examined whether cyclic RGD peptide (cRGD) can promote morpholino-oligomer accumulation in CNV following tail vein injection, and whether systemic cRGD conjugated FLT-MO (cRGD-FLT-MO) suppresses CNV growth.Methods: cRGD conjugated fluorescent morpholino-oligomer (cRGD-F-MO) was injected via tail vein into mice with previous retinal laser photocoagulation and examined for cRGD-F-MO accumulation in CNV. To examine whether cRGD-FLT-MO suppresses CNV growth, mice were tail-vein injected with cRGD-FLT-MO, cRGD conjugated standard morpholino-oligomer (cRGD-STD-MO), or Dulbecco's Phosphate-Buffered Saline (DPBS) 1 and 4 days postlaser photocoagulation. Seven days postlaser photocoagulation, eyes were harvested and laser CNV was stained with isolectin GS-IB4, allowing quantification of CNV size by confocal microscopy.Results: cRGD-F-MO accumulation in CNV commenced immediately after tail vein injection and could be observed even 1 day after injection. cRGD-FLT-MO tail vein injection significantly suppressed CNV size (2.7× 10 5±0.3× 10 5 μm 3, P< 0.05 by Student's t-test) compared with controls (DPBS: 5.1× 10 5±0.6× 10 5 μm 3 and cRGD-STD-MO: 5.5× 10 5±0.8× 10 5 μm 3).Conclusions: cRGD peptide facilitates morpholino-oligomer accumulation in CNV following systemic delivery. cRGD-FLT-MO suppressed CNV growth after tail-vein injection, demonstrating the potential utility of cRGD peptide for morpholino-oligomer delivery to CNV.Translational Relevance: Current therapy for neovascular age-related macular degeneration involves intravitreal injection of anti-vascular endothelial growth factor drugs. Our results indicate that CNV can be treated systemically, thus eliminating risks and hazards associated with intravitreal injection.
