Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales (GRSTB), Bio-P2 Research Unit , École Polytechnique de Montréal , Montréal H3T 1J4 , Québec , Canada.
Canadian Research Chair in Bioinspired Materials, Faculty of Pharmacy , Université de Montréal , Montréal H3T 1J4 , Québec , Canada.
Biomacromolecules. 2019 May 13;20(5):1926-1936. doi: 10.1021/acs.biomac.9b00137. Epub 2019 Apr 23.
Affinity-based systems represent a promising solution to control the delivery of therapeutics using hydrogels. Here, we report a hybrid system that is based on the peptidic E/K coiled coil affinity pair to mediate the release of gold nanoparticles (NPs) from alginate scaffolds. On one hand, the gold NPs were functionalized with the Ecoil-tagged epidermal growth factor (EGF). The bioactivity of the grafted EGF and the bioavailability of the Ecoil moiety were confirmed by EGF receptor phosphorylation assays and by capturing the functionalized NPs on a Kcoil-derivatized surface. On the other hand, alginate chains were modified with azido-homoalanine Kcoil (Aha-Kcoil) by azide-alkyne click chemistry. The hybrid system was formed by dispersing NPs functionalized with the Ecoil-tagged EGF in alginate hydrogels containing either 0, 10, or 20% of Kcoil-modified alginate (Alg-Kcoil). With 20% of Alg-Kcoil, the release of Ecoil-functionalized NPs was reduced by half when compared to the release of NPs without Ecoil, whereas little to no differences were noticed with either 0 or 10% of Alg-Kcoil. Differential dynamic microscopy was used to determine the diffusion coefficient of the NPs, and the results showed a decrease in the diffusion coefficient of Ecoil-functionalized NPs, when compared to bare PEGylated NPs. Altogether, our data demonstrated that the E/K coiled coil system can control the release of NPs in a high Kcoil content alginate gel, opening diverse applications in drug delivery.
基于亲和性的系统代表了一种很有前途的解决方案,可以控制水凝胶中治疗剂的释放。在这里,我们报告了一种基于肽 E/K 卷曲螺旋亲和对的混合系统,用于介导金纳米粒子 (NPs) 从藻酸盐支架中的释放。一方面,金 NPs 被 Ecoil 标记的表皮生长因子 (EGF) 功能化。通过 EGF 受体磷酸化测定和在 Kcoil 衍生表面上捕获功能化的 NPs,证实了接枝 EGF 的生物活性和 Ecoil 部分的生物可用性。另一方面,通过叠氮化物-炔点击化学将叠氮基同型丙氨酸 Kcoil (Aha-Kcoil) 修饰到藻酸盐链上。通过将 Ecoil 标记的 EGF 功能化的 NPs 分散在含有 0、10 或 20% Kcoil 修饰的藻酸盐 (Alg-Kcoil) 的藻酸盐水凝胶中形成混合系统。与不含 Ecoil 的 NPs 相比,当 Alg-Kcoil 含量为 20%时,Ecoil 功能化 NPs 的释放减少了一半,而当 Alg-Kcoil 含量为 0 或 10%时,几乎没有差异。差异动态显微镜用于确定 NPs 的扩散系数,结果表明,与裸露的聚乙二醇化 NPs 相比,Ecoil 功能化 NPs 的扩散系数降低。总的来说,我们的数据表明,E/K 卷曲螺旋系统可以控制高 Kcoil 含量藻酸盐凝胶中 NPs 的释放,为药物输送开辟了多种应用。