Polymer-Based Therapeutics.
Polymer-Based Therapeutics.
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DOI：
10.1021/ma801782q
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发表时间：
2009-01-13
期刊：
影响因子：
5.5
通讯作者：
Kiick, Kristi L.
中科院分区：
文献类型：
--
作者：
Liu, Shuang;Maheshwari, Ronak;Kiick, Kristi L.
聚合物材料由于其生物相容性和合适的机械性能，几十年来一直应用于药物输送和组织再生等治疗领域。此外，由于与小分子药物相比，某些聚合物-药物偶联物具有更高的药效、溶解度和靶向特异性，因此已被用作生物活性药物。增强的对聚合物性质的合成控制使得生产用于靶向和受控递送药物的聚合物组件成为可能，而聚合物隔离剂利用其在体内隔离靶分子时缺乏溶解度的优势。在最近更详细的研究中，聚合物区别于小分子药物的特性，如它们的高分子量和显示多个悬垂部分的能力，已被专门用于激活细胞靶点或抑制病原体的结合。在这类研究中，相关结构-功能关系的阐明依赖于活性聚合方法与化学偶联方法的结合，蛋白质工程方法在操纵这类聚合物疗法的结构特征方面显示出越来越大的潜力。通过使设计的聚合物在生物环境中具有高度特异性的活性，对多价聚合物参与生物靶点的各种机制的详细了解，肯定会扩大聚合物作为治疗药物的作用。
Polymeric materials have been applied in therapeutic applications, such as drug delivery and tissue regeneration, for decades owing to their biocompatibility and suitable mechanical properties. In addition, select polymer–drug conjugates have been used as bioactive pharmaceuticals owing to their increased drug efficacy, solubility, and target specificity compared with small-molecule drugs. Increased synthetic control of polymer properties has permitted the production of polymer assemblies for the targeted and controlled delivery of drugs, and polymeric sequestrants take advantage of their lack of solubility for the sequestration of target molecules in vivo. In more recent studies reviewed in greater detail here, the properties of polymers that distinguish them from small-molecule drugs, such as their high molecular weight and their ability to display multiple pendant moieties, have been specifically exploited for activating cellular targets or inhibiting the binding of pathogens. The elucidation of relevant structure–function relationships in investigations of this kind has relied on the combination of living polymerization methods with chemical conjugation methods, and protein engineering methods have shown increasing potential in the manipulation of architectural features of such polymer therapeutics. Garnering a detailed understanding of the various mechanisms by which multivalent polymers engage biological targets is certain to expand the role of polymers as therapeutics, by enabling highly specific activities of designed polymers in the biological environment.
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