A bioorthogonal nanosystem for imaging and in vivo tumor inhibition
A bioorthogonal nanosystem for imaging and in vivo tumor inhibition
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用于成像和体内肿瘤抑制的生物正交纳米系统
DOI：
10.1016/j.biomaterials.2017.05.036
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发表时间：
2017-09-01
期刊：
影响因子：
14
通讯作者：
Wu, Shuizhu
中科院分区：
文献类型：
--
作者：
Li, Bowen;Liu, Peilian;Wu, Shuizhu
生物正交键断裂反应已成为操纵生物过程的有前途的工具，但这些反应在体内的治疗效果仍需要探索。本文开发了一种用于生物成像和治疗的生物正交激活前药，它由钯介导的可裂解炔丙基、香豆素荧光团和有效的抗癌药物组成。体外研究表明，钯复合物的存在会诱导炔丙基裂解，随后引发级联反应，从而激活香豆素荧光团进行成像并释放抗癌药物进行治疗。然后将前药和 Pd 复合物分别封装到磷脂脂质体中，形成双组分生物正交纳米系统。脂质体纳米系统可以很容易地被HeLa细胞内化，并在一个或两个光子激发下显示出强烈的细胞内荧光，表明Pd介导的生物正交键断裂反应导致细胞内活性药物的释放。更重要的是，该纳米系统在小鼠模型中表现出相当高的活性，并对肿瘤生长发挥有效的抑制作用。这项工作表明，如果配制得当，生物正交系统可以在体内表现良好。该策略可能为设计具有成像和治疗能力的生物正交前药提供一种新方法。 (C) 2017 Elsevier Ltd. 保留所有权利。
Bioorthogonal bond-cleavage reactions have emerged as promising tools for manipulating biological processes, still the therapeutic effect of these reactions in vivo needs to be explored. Herein a bioorthogonal-activated prodrug has been developed for bioimaging and therapy, which is composed of a Pd-mediated cleavable propargyl, a coumarin fluorophore and a potent anticancer drug. In vitro investigations show that, the presence of a Pd complex induces the cleavage of propargyl and subsequently trigger the cascade of reactions, thereby activating the coumarin fluorophore for imaging and releasing the anticancer drug for therapy. Both the prodrug and Pd complex were then separately encapsulated into phospholipid liposomes to form a two-component bioorthogonal nanosystem. The lyposomal nanosystem can be readily internalized by HeLa cells and displays strong intracellular fluorescence under one-or two-photon excitation, indicating the release of the active drug in cells as a result of the Pd-mediated bioorthogonal bond-cleavage reaction. More importantly, the nanosystem shows considerable high activity and exerts efficient inhibition towards tumor growth in a mouse model. This work demonstrates that, if properly formulated, a bioorthogonal system can perform well in vivo. This strategy may offer a new approach for designing bioorthogonal prodrugs with imaging and therapeutic capability. (C) 2017 Elsevier Ltd. All rights reserved.