Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles.
Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles.
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DOI：
10.2147/ijn.s126865
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发表时间：
2017
影响因子：
8
通讯作者：
Sun K
中科院分区：
文献类型：
--
作者：
Chu Y;Chen N;Yu H;Mu H;He B;Hua H;Wang A;Sun K
开发了一种纳米颗粒（NP），通过局部眼部给药靶向脉络膜新生血管（CNV）。通过将内化甘氨酸-甘氨酸-天冬氨酸RGD（iRGD; Ac-CCRGDKGPDC）和反式激活转录（达特）（RKKRRQRRRC）肽缀合至聚合的乙二醇和乳酸-共-乙醇酸来制备NP。iRGD序列可与整合素αvβ3特异性结合，而达特促进穿透眼屏障。1H核磁共振和高效液相色谱证明高达80%的iRGD和达特与聚（乙二醇）-聚（乳酸-共-乙醇酸）缀合。得到的颗粒尺寸为67.0±1.7 nm，颗粒的zeta电位为−6.63±0.43 mV。与裸的和iRGD修饰的NP相比，iRGD和达特NP的角膜渗透分别增加了5.50倍和4.56倍。细胞摄取显示，iRGD和达特NP的红色荧光强度在原代NP和iRGD-或TAT-修饰的NP中最高。光学相干断层扫描和荧光素眼底血管造影分析显示，布朗挪威（BN）大鼠光凝后14天CNV完全形成。BN大鼠脉络膜平片显示，NPs的红色荧光强度遵循iRGD和达特NPs > TAT修饰的NPs > iRGD修饰的NPs >原代NPs。因此，iRGD和达特双重修饰的NP在体外和体内均显示出显著的靶向和渗透能力，表明其是通过局部眼部施用来管理CNV的有前景的药物递送系统。
A nanoparticle (NP) was developed to target choroidal neovascularization (CNV) via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC) and transactivated transcription (TAT) (RKKRRQRRRC) peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. 1H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol)– poly(lactic-co-glycolic acid). The resulting particle size was 67.0±1.7 nm, and the zeta potential of the particles was −6.63±0.43 mV. The corneal permeation of iRGD and TAT NPs increased by 5.50- and 4.56-fold compared to that of bare and iRGD-modified NPs, respectively. Cellular uptake showed that the red fluorescence intensity of iRGD and TAT NPs was highest among primary NPs and iRGD- or TAT-modified NPs. CNV was fully formed 14 days after photocoagulation in Brown Norway (BN) rats as shown by optical coherence tomography and fundus fluorescein angiography analyses. Choroidal flat mounts in BN rats showed that the red fluorescence intensity of NPs followed the order of iRGD and TAT NPs > TAT-modified NPs > iRGD-modified NPs > primary NPs. iRGD and TAT dual-modified NPs thus displayed significant targeting and penetration ability both in vitro and in vivo, indicating that it is a promising drug delivery system for managing CNV via topical ocular administration.