Architectural and structural optimization of the protective polymer layer for enhanced targeting
Architectural and structural optimization of the protective polymer layer for enhanced targeting
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DOI：
10.1021/la047109v
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发表时间：
2005-06-07
期刊：
影响因子：
3.9
通讯作者：
Dormidontova, EE
中科院分区：
文献类型：
--
作者：
Chen, CC;Dormidontova, EE
使用Monte Carlo模拟，我们研究了配体结构（价，分支长度）和结构（多分散性）的平坦的保护性聚合物层上的可及性，其官能团和受体靶向效率的影响。两种类型的受体表面被认为是：表面均匀覆盖的受体和表面含有有限数量的受体位点。我们发现，对于每个聚合物层的靶向基团总数相同的情况下，与单价配体相比，多价配体在层外围提供了更大密度的靶向基团。由于它们在结合中的协同性，多价配体在与两种类型的受体表面的结合中也相当有效。随着配体化合价的增加，与受体连接的官能团的数量显著增加。短支链二价配体在与紧密堆积的受体结合时显示出特别高的协同性。然而，在固定受体彼此相隔有限距离的情况下，属于相同短二价配体的官能团之间的平均距离太小而不能同时到达不同的受体，并且受体结合的效率低于单价配体的情况。使用由短的非官能化聚合物和长的官能化聚合物形成的双分散保护性聚合物层显著地增加了层的外围上的官能团的分数。受体结合的模拟证实了通过双分散聚合物层的受体靶向的高效率，这是通过与相应的单分散层相比更大的可压缩性和更高的配体伸出能力来实现的。多价配体和双分散保护性聚合物层的概念各自具有其自身的优点，其可以组合用于增强的靶向效果。
Using Monte Carlo simulations we study the influence of ligand architecture (valence, branching length) and structure (polydispersity) of a flat protective polymer layer on the accessibility of its functional groups and efficiency of receptor targeting. Two types of receptor surfaces were considered: the surface homogeneously covered with receptors and the surface containing a finite number of receptor sites. We found that multivalent ligands provide a larger density of targeting groups on the periphery of the layer compared to monovalent ligands for the same overall number of targeting groups per polymer layer. Because of their cooperativity in binding, multivalent ligands were also considerably more efficient in binding to both types of receptor surfaces. With an increase of ligand valence the number of functional groups attached to receptors noticeably increases. Short-branched divalent ligands show an especially high cooperativity in binding to closely packed receptors. However, in the case of immobile receptors separated by a finite distance from each other, the average distance between the functional groups belonging to the same short divalent ligand is too small to reach different receptors simultaneously and the receptor binding is less efficient than in the monovalent ligand case. Using a bidisperse protective polymer layer formed by short nonfunctional polymers and long functionalized polymers considerably increases the fraction of functional groups on the periphery of the layer. Simulations of receptor binding confirm the high efficiency of receptor targeting by bidisperse polymer layers, which is achieved by means of larger compressibility and higher capability of the ligands to reach out compared to the corresponding monodisperse layers. The concepts of multivalent ligands and a bidisperse protective polymer layer each have their own advantages which can be combined for an enhanced targeting effect.