Paclitaxel loaded liposomes decorated with a multifunctional tandem peptide for glioma targeting
Paclitaxel loaded liposomes decorated with a multifunctional tandem peptide for glioma targeting
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负载紫杉醇的脂质体装饰有多功能串联肽，用于神经胶质瘤靶向。
DOI：
10.1016/j.biomaterials.2014.02.031
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发表时间：
2014-06-01
期刊：
影响因子：
14
通讯作者：
He, Qin
中科院分区：
文献类型：
--
作者：
Liu, Yayuan;Ran, Rui;He, Qin
由于血脑屏障(BBB)的存在，胶质瘤的治疗是一个巨大的挑战。为了减少对正常脑组织的毒性，实现有效的治疗，药物进入大脑后特异性地积聚在胶质瘤灶内并渗透到肿瘤核心也很重要。在本研究中，将特定配体的环状RGD多肽与细胞穿透性多肽R8偶联，开发出多功能多肽R8-RGD。与R8和RGD相比，R8-RGD使细胞对脂质体的摄取量分别增加了2倍和近30倍，并在体外显示了对三维胶质瘤球体和BBB模型的有效渗透。体内研究表明，R8-RGD-Lipoo能有效地转运到脑内，并选择性地蓄积在C6胶质瘤荷瘤小鼠体内。将紫杉醇(PTX)包埋于脂质体中后，R8-RGD-Lipoo对C6细胞的抑制作用最强，并诱导C6细胞发生凋亡，最终使C6胶质瘤小鼠存活时间延长。综上所述，R8-RGD串联肽是一种具有血脑屏障转运、脑胶质瘤靶向和肿瘤穿透等多种功能的新型配体。R8-RGD-Lipoo是一种潜在的抗脑胶质瘤药物释放系统。(C)2014爱思唯尔有限公司。保留所有权利。
The treatment of glioma is a great challenge because of the existence of the blood-brain barrier (BBB). In order to reduce toxicity to the normal brain tissue and achieve efficient treatment, it is also important for drugs to specifically accumulate in the glioma foci and penetrate into the tumor core after entering into the brain. In this study, a specific ligand cyclic RGD peptide was conjugated to a cell penetrating peptide R8 to develop a multifunctional peptide R8-RGD. R8-RGD increased the cellular uptake of liposomes by 2-fold and nearly 30-fold compared to separate R8 and RGD respectively, and displayed effective penetration of three-dimensional glioma spheroids and BBB model in vitro. In vivo studies showed that R8-RGD-lipo could be efficiently delivered into the brain and selectively accumulated in the glioma foci after systemic administration in C6 glioma bearing mice. When paclitaxel (PTX) was loaded in liposomes, R8-RGD-lipo could induce the strongest inhibition and apoptosis against C6 cells and finally achieved the longest survival in intracranial C6 glioma bearing mice. In conclusion, all the results indicated that the tandem peptide R8-RGD was a promising ligand possessing multi functions including BBB transporting, glioma targeting and tumor penetrating. And R8-RGD-lipo was proved to be a potential anti-glioma drug delivery system. (C) 2014 Elsevier Ltd. All rights reserved.