Optically triggered release of DNA from multivalent dendrons by degrading and charge-switching multivalency
Optically triggered release of DNA from multivalent dendrons by degrading and charge-switching multivalency
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DOI：
10.1002/anie.200701200
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Ikkala, Olli
中科院分区：
文献类型：
--
作者：
Kostiainen, Mauri A.;Smith, David K.;Ikkala, Olli
纳米级物体之间的多价键合最近已经成为组装具有纳米技术应用的功能性超分子材料的最有力的方法之一。[1，2]通过使用外部刺激，如pH值，温度，光，电势或磁场来控制纳米材料的自组装，是制备用于广泛潜在应用的功能和响应性材料的重要要求。[3，4]刺激响应材料已被广泛追求，特别关注医学应用;例如，受控药物和DNA递送系统，[5，6]笼状酶的再活化，[7]和可转换膜蛋白。[8]使用光作为外部刺激提供了许多优点，因为光易于应用，对生物体相对无害，并且重要的是在空间和时间上都是可控的。[5，7，9]可以通过光操纵的DNA结合化合物在非病毒基因治疗中特别有趣，该治疗依赖于保护，运输和释放DNA到靶细胞中的合成化合物。[10]在这方面，阳离子树枝状体系特别令人感兴趣。[11-13]已经用聚酰胺胺（PAMAM）[14]树枝状聚合物进行了开创性的基因治疗研究，同时也研究了树枝状聚（l-赖氨酸）[15]和聚（丙烯亚胺）[16]。这些化合物中的许多结合DNA。然而，如果结合非常强，则难以实现复合物的解包和DNA的释放，这导致低转染效率。[17]因此，DNA的释放具有直接的重要性。最近有一些研究集中在光可裂解的树枝状聚合物和树枝状分子上。这些研究包括自分解树枝状聚合物[18]和基于光可裂解核[19，20]或光活性表面的树枝状聚合物。[21]这些系统在由UV照射触发的过程中从树枝状结构释放共价结合的单元。值得注意的是，金纳米颗粒也可以以类似于树枝状结构的方式用于DNA结合和递送。[9]尽管取得了很大的进展，但其中非共价多价结合可以通过外部刺激来控制的系统尚未完全开发。多价被定义为一种结合类型，其中多个配体连接到单个分子支架上，并用于与另一个实体相互作用，该实体显示与配体互补的多个结合位点。[1，2]在最近的研究中，我们报道了一系列Newkome型[22]树枝状配体，其表面具有多个质子化精胺基团，表现出多价DNA结合。[17鉴于我们对多价DNA识别的兴趣，我们决定探索我们的受体是否可以以实现光响应性的方式开发。因此，我们修改了我们以前报道的树突通过连接精胺表面基团通过邻硝基苄基接头（方案1a）。邻硝基苄基在长波长紫外光（λ= 350 nm）下发生光解降解（方案1b），从而使共价连接的精胺表面基团和非共价结合的DNA受控释放。一旦精胺基团从树枝化基元的表面裂解，阳离子多价效应被破坏，从而仅留下单个精胺基团，仅对DNA具有弱亲和力。以这种方式，DNA分子将在光解时有效地解复合。重要的是，当表面基团被切割时，它们留下阴离子羧酸表面，这将进一步排斥DNA（方案1c）。紫外线
Multivalent binding between nanoscale objects has recently emerged as one of the most powerful methods for the assembly of functional supramolecular materials with applications in nanotechnology.[1, 2] Controlling the self-assembly of nanomaterials by using external stimuli, such as pH, temperature, light, electric potential, or magnetic field, is an important requirement for the preparation of functional and responsive materials for a wide range of potential applications.[3, 4] Stimuli-responsive materials have been extensively pursued, with special focus on medicinal applications; for example, controlled drug and DNA delivery systems,[5, 6] reactivation of caged enzymes,[7] and switchable membrane proteins.[8] The use of light as an external stimulus offers a number of advantages, because light is easy to apply, relatively harmless to living organisms, and—importantly—controllable both spatially and temporally.[5, 7, 9] DNA-binding compounds that can be manipulated by light are especially interesting in nonviral gene therapy, which relies on synthetic compounds that protect, transport, and release DNA into target cells.[10] Cationic dendritic systems have been of particular interest in this regard.[11–13] Pioneering gene-therapy research has been conducted with polyamidoamine (PAMAM)[14] dendrimers, while dendritic poly (l-lysine)[15] and poly (propylene imine)[16] have also been studied. Many of these compounds bind DNA. However, unpacking of the complexes and release of the DNA is difficult to achieve if the binding is very strong, which results in a low transfection efficiency.[17] DNA release is therefore of direct importance. There have been some recent studies with a focus on photocleavable dendrimers and dendrons. The studies include self-immolative dendrimers [18] and dendrimers based on photocleavable cores [19, 20] or photoactive surfaces.[21] These systems release covalently bound units from the dendritic structure in a process triggered by UV irradiation. It is worth noting that gold nanoparticles can also be employed in DNA binding and delivery in an analogous manner to dendritic structures.[9] Despite much progress, systems in which noncovalent multivalent binding could be controlled by external stimuli have not yet been fully developed. Multivalency is defined as a type of binding in which multiple ligands are attached to a single molecular scaffold and used to interact with another entity that displays multiple binding sites which are complementary to the ligands.[1, 2] In recent studies, we reported a series of Newkome-type [22] dendritic ligands, with multiple protonated spermine groups on their surfaces, which exhibit multivalent DNA binding.[17, 23, 24] Given our interest in multivalent DNA recognition, we decided to explore whether our receptor could be developed in such a way as to achieve photoresponsivity. We therefore modified our previously reported dendrons by attaching the spermine surface groups through an o-nitrobenzyl linker (Scheme 1a). The o-nitrobenzyl group undergoes photolytic degradation (Scheme 1b) when submitted to long-wavelength UV light (λ= 350nm), thus allowing a controlled release of the covalently attached spermine surface groups and the noncovalently bound DNA. Once the spermine groups are cleaved from the surface of the dendron, the cationic multivalency effect is destroyed, thereby leaving just individual spermine groups, with only a weak affinity for DNA. In this way, the DNA molecule will be effectively decomplexed upon photolysis. Importantly, as the surface groups are cleaved, they leave behind an anionic carboxylic acid surface that will further repel DNA (Scheme 1c). UV …