Dual-targeting for brain-specific liposomes drug delivery system: Synthesis and preliminary evaluation.
Dual-targeting for brain-specific liposomes drug delivery system: Synthesis and preliminary evaluation.
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DOI：
10.1016/j.bmc.2018.08.006
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发表时间：
2018-09
影响因子：
3.5
通讯作者：
Yao Peng;Yi Zhao;Yang Chen;Zhongzhen Yang;Li Zhang;Wenjiao Xiao;Jincheng Yang;Li Guo;Yong Wu
中科院分区：
文献类型：
--
作者：
Yao Peng;Yi Zhao;Yang Chen;Zhongzhen Yang;Li Zhang;Wenjiao Xiao;Jincheng Yang;Li Guo;Yong Wu
由于脑屏障的存在，脑胶质瘤的治疗已成为一个巨大的挑战。为了开发一种高效的脑靶向给药系统，大大提高抗癌药物的脑部通透性，设计并合成了一种新型的脑靶向葡萄糖-维生素C(Glu-VC)衍生物作为脂质体配体，用于制备有效传递紫杉醇(PTX)的脂质体。制备了脂质体，并对其粒径、Zeta电位、包封率、释放度、稳定性、溶血性和细胞毒性进行了表征。C6细胞对CFPE标记的Glu-VC-Lip的摄取分别是LiP、Glu-Lip、VC-Lip和Glu- + VC-Lip的4.79、1.95、4.00和1.53倍。此外，与紫杉醇裸、未包衣、单一修饰和共修饰的物理混合脂质体相比，谷氨酸-VC修饰的脂质体具有更好的体内靶向性。相对摄取效率为裸紫杉醇的7.53倍，浓集效率为7.89倍。更重要的是，Glu-VC修饰的脂质体在肿瘤部位也显示出最大的DID聚集，在脑活体成像中具有最强的荧光。我们的结果表明，用葡萄糖和维生素C弹头对脂质体进行化学修饰是利用弹头的内源性转运机制开发脑特异性脂质体给药系统的一种有前途的有效策略。
The treatment of glioma has become a great challenge because of the existence of brain barrier (BB). In order to develop an efficient brain targeting drug delivery system to greatly improve the brain permeability of anti-cancer drugs, a novel brain-targeted glucose-vitamin C (Glu-Vc) derivative was designed and synthesized as liposome ligand for preparing liposome to effectively deliver paclitaxel (PTX). The liposome was prepared and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis and cytotoxicity were also characterized. What’s more, the cellular uptake of CFPE-labeled Glu-Vc-Lip on GLUT1- and SVCT2-overexpressed C6 cells was 4.79-, 1.95-, 4.00- and 1.53-fold higher than that of Lip, Glu-Lip, Vc-Lip and Glu + Vc-Lip. Also, the Glu-Vc modified liposomes showed superior targeting abilityin vivoevaluation compared with naked paclitaxel, non-coated, singly-modified and co-modified by physical blending liposomes. The relative uptake efficiency was enhanced by 7.53 fold to that of naked paclitaxel, while the concentration efficiency was up to 7.89 times. What’s more, the Glu-Vc modified liposomes also displayed the maximum accumulation of DiD-loaded liposomes at tumor sites with the strongest fluorescence in the brainin vivoimaging. Our results suggest that chemical modification of liposomes with warheads of glucose and vitamin C represents a promising and efficient strategy for the development of brain-specific liposomes drug delivery system by utilizing the endogenous transportation mechanism of the warheads.