Multifunctional and Dual-Responsive Polymersomes as Robust Nanocontainers: Design, Formation by Sequential Post-Conjugations, and pH-Controlled Drug Release
Multifunctional and Dual-Responsive Polymersomes as Robust Nanocontainers: Design, Formation by Sequential Post-Conjugations, and pH-Controlled Drug Release
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DOI：
10.1021/acs.chemmater.5b05016
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发表时间：
2016-03-08
影响因子：
8.6
通讯作者：
Appelhans, Dietmar
中科院分区：
文献类型：
--
作者：
Iyisan, Banu;Kluge, Joerg;Appelhans, Dietmar
强大的，多响应的，多功能的纳米囊泡不仅作为载体系统，而且在微系统设备和纳米技术的应用中有很高的需求。因此，多功能的，pH值响应性，和光交联的聚合物修饰的金刚烷和叠氮基团的聚合物囊泡通过适当的末端修饰的嵌段共聚物的混合自组装制备，并用于随后的后共轭的聚合物囊泡表面通过使用共价和非共价的方法。对于共价方法，作为光响应部分的硝基乙炔基氧基羰基保护的胺（NVOC）分子通过叠氮化物炔点击反应引入聚合物囊泡中。在NVOC单元的光裂解之后，功能性染料分子与现在可自由接近的胺基反应。随后进行非共价方法以引入其他部分，利用强金刚烷-β-环糊精主客体相互作用。它是定量证明，所有的反应基团具有足够的可及性以及选择性和正交反应性，在这些逐步的过程中，以允许成功建立目标的pH值和光响应的多功能聚合物囊泡。此外，这种顺序的方法也适用于获得多柔比星负载的多功能聚合物囊泡，用于有效的pH控制的药物释放。总的来说，可调的膜渗透性与通过曝光或主客体相互作用引入多个靶向基团的潜力相结合，使得这些智能聚合物囊泡有希望用于许多应用的纳米容器。
Robust, multiresponsive, and multifunctional nano vesicles are in high demand not only as carrier systems but also for applications in microsystem devices and nanotechnology. Hence, multifunctional, pH-responsive, and photo-cross-linked polymersomes decorated with adamantane and azide groups are prepared by mixed self assembly of suitably end-modified block copolymers and are used for the subsequent postconjugation of the polymersome surface by using covalent and noncovalent approaches. For the covalent approach, nitroveratryloxycarbonyl-protected amine (NVOC) molecules as light responsive moieties are introduced into the polymersomes through an azide alkyne click reaction. After photocleavage of NVOC units, functional dye molecules react with the now freely accessible amine groups. The noncovalent approach is performed subsequently to introduce further moieties, making use of the strong adamantane-beta-cydodextrin host guest interactions. It is quantitatively proven that all reactive groups have sufficient accessibility as well selective and orthogonal reactivity throughout these stepwise processes to allow the successful establishment of aimed pH- and light-responsive multifunctional polymersomes. Moreover, this sequential methodology is also applied to obtain doxorubicin-loaded multifunctional polymersomes for an efficient pH-controlled drug release. Overall, tunable membrane permeability combined with the potential for introducing multiple targeting groups by light-exposure or host guest interactions make these smart polymersomes promising nanocontainers for many applications.