Functional mesoporous silica nanoparticles for photothermal-controlled drug delivery in vivo.
Functional mesoporous silica nanoparticles for photothermal-controlled drug delivery in vivo.
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DOI：
10.1002/anie.201203993
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发表时间：
2012-08
影响因子：
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通讯作者：
Hong Yan;C. Teh;S. Sreejith;Liangliang Zhu;Anna Kwok;Weiqing Fang;Xing Ma;K. Nguyen;V. Korzh-V.-Ko
中科院分区：
文献类型：
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作者：
Hong Yan;C. Teh;S. Sreejith;Liangliang Zhu;Anna Kwok;Weiqing Fang;Xing Ma;K. Nguyen;V. Korzh-V.-Ko
功能性介孔二氧化硅纳米颗粒（MSNPs）可以通过可控触发器（如pH值变化，[1]化学处理，[2]静电相互作用，[3]酶促作用，[4]氧化还原变化，[5]和光照射）容易地调节，已有效地用于受控药物递送。在这些刺激条件中，光热作用可以被认为是一种清洁的能源，并且光热动力分子机器可以可逆地操作并且不产生副产物。因此，新型光热动力系统的构建虽然具有挑战性，但由于其在纳米结构功能材料，[7]分子开关，[8]分子逻辑门[9]和分子导线领域的潜在应用，科学家一直在寻求。[10]光开关偶氮苯及其衍生物已广泛应用于催化剂，[11]传感器，[12]软材料，[13]甚至生物系统。[14]目前使用MSNPs作为药物载体用于药物控释的挑战包括：如何在不释放孔封闭单元的情况下释放药物以避免释放的孔封闭单元的副作用，如何实现药物在体内的受控释放，以及如何提高药物载体的效率。[15]考虑到这些因素，生物相容性光热响应门共价连接到MSNPs的表面被认为是控制药物输送的最佳方法之一。虽然基于偶氮苯哑铃形物旋入α-环糊精（α-CD）环的反-顺式光异构化的光诱导可切换轮烷已经得到了很好的研究[16]，但用于受控药物递送的光热响应轮烷机械化MSNP的合成和应用尚未报道。在这种情况下，一个简单的，有效的，生物相容性，和远程控制的MSNP通过使用光热响应轮烷的发展是相当重要的。在此，我们报告了一种新的策略，用于制备光热响应轮烷功能化的MSNPs，并证明了这种远程控制系统在体内释放药物的野生型，光学透明的斑马鱼幼虫。特别是，功能性纳米颗粒可以有效地将姜黄素递送到斑马鱼幼虫中用于治疗心力衰竭。新型MSNP用[2]轮烷官能化，其中α-CD环与一端含有预先连接的塞子的线性光热响应偶氮苯轴螺纹连接（方案1）。终止单元具有两个磺酸基，进一步提高了单个纳米颗粒在水溶液中的溶解度。[2]轮烷中的α-CD环最初位于反式偶氮苯位置，该位置从纳米颗粒表面（trans-MSNP-1）稍微移除。在方案1的反式至顺式光异构化后，其移动至三唑/乙二醇位置。将载药的MSNP注射到斑马鱼幼虫中用于体内药物递送的图形表示，通过加热或可见光照射触发。MSNP在表面上用光热响应[2]轮烷官能化。给出了含α-CD环和偶氮苯单元的[2]轮烷的化学结构。
Functional mesoporous silica nanoparticles (MSNPs) that can be readily modulated by controllable triggers, such as pH value changes,[1] chemical treatments,[2] electrostatic interactions,[3] enzymatic actions,[4] redox changes,[5] and photoirradiation,[6] have been used effectivly for controlled drug delivery. Among these stimulus conditions, photothermal action can be considered a clean source of energy, and photothermal-powered molecular machines can be reversibly operated and do not generate byproducts. Thus, the construction of novel photothermal-powered systems, although challenging, has been sought after by scientists on account of their potential applications in the areas of nanostructured functional materials,[7] molecular switches,[8] molecular logic gates,[9] and molecular wires.[10] Photo-switchable azobenzene and its derivatives have been widely applied in catalysts,[11] sensors,[12] soft materials,[13] and even in biological systems.[14] Current challenges of using MSNPs as drug carriers for controlled drug delivery include: how to release drugs without the release of the poreblocking units to avoid side effects from the released poreblocking units, how to achieve controlled drug release in vivo, and how to improve the efficiency of drug carriers.[15] Considering these factors, biocompatible photothermalresponsive gates linked covalently to the surface of MSNPs are regarded as one of the best approaches for controlled drug delivery. Although light-induced switchable rotaxanes based on the trans–cis photoisomerization of an azobenzene dumbbell threaded into the α-cyclodextrin (α-CD) ring have been well investigated,[16] the synthesis and application of photothermal-responsive rotaxane-mechanized MSNPs for controlled drug delivery have not been reported. In this context, the development of a simple, efficient, biocompatible, and remote-controlled MSNP through the use of photothermalresponsive rotaxanes is of considerable significance. Herein, we report a novel strategy for the preparation of photothermal-responsive rotaxane-functionalized MSNPs and demonstrate this remote-controlled system for in vivo drug release to wild-type, optically transparent zebrafish larvae. In particular, the functional nanoparticles can efficiently deliver curcumin to zebrafish larvae for the treatment of heart failure. The novel MSNPs were functionalized with [2] rotaxanes in which the α-CD ring is threaded with a linear photothermal-responsive azobenzene axle containing a preattached stopper at one end (Scheme 1). The stopper unit has two sulfonic groups, further enhancing the solubility of individual nanoparticles in aqueous solution. The α-CD ring in the [2] rotaxane is initially located at the trans-azobenzene position, which is somewhat removed from the nanoparticle surface (trans-MSNP-1). It moves to the triazole/ethylene glycol position upon the trans-to-cis photoisomerization ofScheme 1. A graphical representation of the injection of drug-loaded MSNPs into zebrafish larvae for in vivo drug delivery, triggered by either heating or visible light irradiation. MSNPs were functionalized with photothermal-responsive [2] rotaxanes on the surface. The chemical structure of the [2] rotaxane containing the α-CD ring and azobenzene unit is shown.