Thiol-functionalized polymeric micelles: From molecular recognition to improved mucoadhesion
Thiol-functionalized polymeric micelles: From molecular recognition to improved mucoadhesion
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DOI：
10.1021/bc050007b
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发表时间：
2005-07-01
影响因子：
4.7
通讯作者：
Leroux, JC
中科院分区：
文献类型：
--
作者：
Dufresne, MH;Gauthier, MA;Leroux, JC
表面改性的胶体可以选择性地与生物物种或表面相互作用，显示出作为药物递送系统的前景。然而，这种靶向装置的制备仍然具有挑战性，特别是当考虑聚离子络合物胶束时，其与离子核心组分（通常为羧酸或氨基）的副反应可能发生。为了解决这个问题，提出了一种创新的合成策略，并用于制备在聚（乙二醇）链末端具有硫醇基团的不对称聚（乙二醇）-嵌段-聚（甲基丙烯酸2-（N，N-二甲基氨基）乙酯）共聚物。硫醇基团是非常有吸引力的，因为它们在生理条件下几乎完全和定量地与马来酰亚胺反应，从而促进共聚物的化学官能化。通过制备模型生物素封端的共聚物来说明衍生化过程的简单性。生物素化的共聚物显示出与寡核苷酸在水性介质中自组装以形成在其外表面具有生物素基团的聚离子复合物胶束。这些胶束能够对链霉亲和素进行分子识别。或者，制备硫醇修饰的（非衍生化的）胶束，并通过与粘蛋白形成二硫键显示出改善的粘膜粘附。最后，在氧化条件下生成胶束间二硫键，以促进刺激响应性胶束网络的形成。
Surface-modified colloids which can selectively interact with biological species or surfaces show promise as drug delivery systems. However, the preparation of such targeted devices remains challenging, especially when considering polyion complex micelles for which side reactions with the ionic core components (typically carboxylic acid or amino groups) can occur. To solve this issue, an innovative synthetic strategy is proposed and used to prepare an asymmetric poly(ethylene glycol)-block -poly(2-(N,N-dimethylamino)ethyl methacrylate) copolymer presenting a thiol group at the end of the poly(ethylene glycol) chain. Thiol groups are highly appealing given that they react almost exclusively and quantitatively with maleimides under physiological conditions, thereby facilitating the chemical functionalization of the copolymer. The simplicity of the derivatization procedure is illustrated by preparing model biotin-capped copolymers. The biotinylated copolymers are shown to self-assemble with an oligonucleotide in aqueous media to form polyion complex micelles with biotin groups at their outer surface. These micelles are capable of molecular recognition toward streptavidin. Alternatively, thiol-decorated (nonderivatized) micelles are prepared and show improved mucoadhesion through the formation of disulfide bonds with mucin. Finally, intermicellar disulfide bonds are generated under oxidative conditions to promote the formation of stimuli-responsive micellar networks.