Key Laboratory of Colloid and Interface Chemistry & Key Laboratory of Special Aggregated Materials, Ministry of Education, Shandong University , Jinan 250100, P. R. China.
Biomacromolecules. 2017 Mar 13;18(3):1029-1038. doi: 10.1021/acs.biomac.6b01939. Epub 2017 Feb 28.
We created the dual-responsive nanovehicle that can effectively combine and abundantly utilize magnetic and glutathione (GSH)-reductive triggers to control the drug delivery and achieve more intelligent and powerful targeting. In the nanovehicles, paramagnetic fullerene (C@CTAF) was prepared via one-step modification of fullerene with magnetic surfactant CTAF by hydrophobic interaction for the first time. The perfect conjugation of C and CTAF increased the solubility or dispersity of fullerenes and qualified CTAF with more powerful assembly capability with DNA. DNA molecule in the nanovehicles acted as an electrostatic scaffold to load anticancer drug Dox as well as the important building block for assembly with C@CTAF into C@CTAF/DNA. The further combination of deshielding and targeting functions in reduction-responsive disulfide modified HA-SS-COOH coating on C@CTAF/DNA complexes could reduce the agglomeration and regulate the morphology of C@CTAF/DNA complexes from irregular microstructures to more uniform ones. More importantly, the introduction of HA-SS-COOH provided a response to a simulating reductive extra-tumoral environment by efficient cleavage of disulfide linkages by GSH and site-specific drug delivery to HepG2 cells. Amazingly, the final nanovehicles presented an increased magnetic susceptibility compared with paramagnetic CTAF, and they "walked" under an applied magnetic field. Because of their facile fabrication, rapid responsiveness to extra tumoral environment, and external automatic controllability by external magnet, the drug delivery nanovehicles constructed by magnetic fullerene-DNA/hyaluronic acid might be of great interest for making new functional nucleic-acid-based drug carriers.
我们构建了一种双响应型纳米载体，能够有效地结合并充分利用磁响应和谷胱甘肽（GSH）还原响应触发来控制药物传递，从而实现更智能、更强大的靶向作用。在纳米载体中，首次通过疏水相互作用，将磁性表面活性剂 CTAF 一步修饰富勒烯，制备了顺磁富勒烯（C@CTAF）。C 和 CTAF 的完美结合增加了富勒烯的溶解度或分散度，同时使 CTAF 具有更强的与 DNA 组装能力。纳米载体中的 DNA 分子作为静电支架，既能负载抗癌药物阿霉素，又能作为组装的重要构建块，将 C@CTAF 与 C@CTAF/DNA 组装在一起。进一步在还原响应性二硫键修饰的透明质酸-SS-COOH 涂层上结合 C@CTAF/DNA 复合物的屏蔽和靶向功能，可以减少聚集并调节 C@CTAF/DNA 复合物的形态，从不规则的微观结构转变为更均匀的结构。更重要的是，透明质酸-SS-COOH 的引入提供了对模拟的肿瘤外还原环境的响应，通过 GSH 高效切割二硫键，并实现对 HepG2 细胞的靶向药物传递。令人惊讶的是，最终的纳米载体与顺磁 CTAF 相比表现出更高的磁化率，并且它们可以在施加的磁场下“行走”。由于其易于制造、对肿瘤外环境的快速响应以及外部磁场的自动外部可控性，由磁性富勒烯-DNA/透明质酸构建的药物递送纳米载体可能对制造新型基于功能核酸的药物载体具有重要意义。
