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Dual Stimuli-Responsive Supramolecular Self-Assemblies Based on the Host-Guest Interaction between β-Cyclodextrin and Azobenzene for Cellular Drug Release.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-03-03 , DOI: 10.1021/acs.molpharmaceut.9b01142 JianGuo Zhang 1 , Zi-Hao Zhou 1 , Lin Li 1 , Yan-Ling Luo 1 , Feng Xu 1 , Yashao Chen 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-03-03 , DOI: 10.1021/acs.molpharmaceut.9b01142 JianGuo Zhang 1 , Zi-Hao Zhou 1 , Lin Li 1 , Yan-Ling Luo 1 , Feng Xu 1 , Yashao Chen 1
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Health has always been a hot topic of concern, whereas cancer is one of the largest security risks to human health. Although the existing drug delivery systems (DDSs) have been extensively reported and commercially applied, there are still some issues that have yet to be well-resolved, including the toxicity, side-effects, and targeted therapy efficiency of drugs. Consequently, it is still necessary to develop a novel, highly efficient, controlled and targeted DDS for cancer therapy. For this, a supramolecular polymer, β-CD-g-PDMAEMA@Azo-PCL, was designed and developed through the host–guest inclusion complexation interactions between a host polymer, β-cyclodextrin-graft-poly(2-(dimethylamino)ethyl methacrylate) (β-CD-g-PDMAEMA), and a guest polymer, azobenzene modified poly(ε-caprolactone) (Azo-PCL), and was characterized by various analysis techniques. The supramolecular assembly was examined in various pH environments and/or under UV–vis irradiation, showing the formation of supramolecular assemblies from regular spherical shapes to irregular aggregates with various hydrodynamic diameters. The 2D NOESY NMR studies showed the formation of inclusion complexation between Azo-PCL and β-CD-g-PDMAEMA and between β-CD and the side groups of PDMAEMA. The supramolecular assemblies could encapsulate doxorubicin to form spherical core–shell drug-carrying micelles with an entrapment efficiency of 66.1%. The effects of external environment stimuli on the in vitro drug release were investigated, showing light- and pH-modulated drug release properties. The cytotoxicity assessment indicated that the blank supramolecular micelles were nontoxic, whereas the drug-loaded micelles exhibited comparable or even superior anticancer activity to the anticancer activity of free DOX and inhibition of cancer cell proliferation. Therefore, the developed supramolecular assemblies can potentially be used as drug-controlled release carriers.
中文翻译：
基于β-环糊精和偶氮苯之间的宿主-客体相互作用的双重刺激响应性超分子自组装，用于细胞药物释放。
健康一直是人们关注的热点话题，而癌症是人类健康面临的最大安全风险之一。尽管已经广泛报道了现有的药物输送系统（DDS）并将其商业应用，但仍有一些问题尚未得到很好解决，包括药物的毒性，副作用和靶向治疗效率。因此，仍然有必要开发一种新颖，高效，可控且靶向的DDS用于癌症治疗。为此，通过主体聚合物，β-环糊精-接枝-聚（2-（二甲基氨基）乙基）之间的主体-客体包合络合相互作用，设计并开发了超分子聚合物β-CD- g - PDMAEMA@ Azo-PCL。甲基丙烯酸酯）（β-CD- g-PDMAEMA）和客体聚合物，偶氮苯改性的聚（ε-己内酯）（Azo-PCL），并通过各种分析技术进行了表征。在不同的pH环境中和/或在UV-vis辐射下检查了超分子组装体，显示了从规则球形到具有各种流体动力学直径的不规则聚集体的超分子组装体的形成。二维NOESY NMR研究表明，Azo-PCL与β-CD- g -PDMAEMA之间以及β-CD与PDMAEMA侧基之间形成了包合物。超分子组装体可以将阿霉素包封以形成球形核壳药物运载胶束，包封率为66.1％。外部环境刺激对体外的影响对药物释放进行了研究，显示了光和pH调节的药物释放特性。细胞毒性评估表明，空白的超分子胶束是无毒的，而载药的胶束显示出与游离DOX的抗癌活性相当的或什至更好的抗癌活性以及对癌细胞增殖的抑制作用。因此，开发的超分子组件可以潜在地用作药物控制释放载体。
更新日期：2020-03-03
中文翻译：
基于β-环糊精和偶氮苯之间的宿主-客体相互作用的双重刺激响应性超分子自组装，用于细胞药物释放。
健康一直是人们关注的热点话题，而癌症是人类健康面临的最大安全风险之一。尽管已经广泛报道了现有的药物输送系统（DDS）并将其商业应用，但仍有一些问题尚未得到很好解决，包括药物的毒性，副作用和靶向治疗效率。因此，仍然有必要开发一种新颖，高效，可控且靶向的DDS用于癌症治疗。为此，通过主体聚合物，β-环糊精-接枝-聚（2-（二甲基氨基）乙基）之间的主体-客体包合络合相互作用，设计并开发了超分子聚合物β-CD- g - PDMAEMA@ Azo-PCL。甲基丙烯酸酯）（β-CD- g-PDMAEMA）和客体聚合物，偶氮苯改性的聚（ε-己内酯）（Azo-PCL），并通过各种分析技术进行了表征。在不同的pH环境中和/或在UV-vis辐射下检查了超分子组装体，显示了从规则球形到具有各种流体动力学直径的不规则聚集体的超分子组装体的形成。二维NOESY NMR研究表明，Azo-PCL与β-CD- g -PDMAEMA之间以及β-CD与PDMAEMA侧基之间形成了包合物。超分子组装体可以将阿霉素包封以形成球形核壳药物运载胶束，包封率为66.1％。外部环境刺激对体外的影响对药物释放进行了研究，显示了光和pH调节的药物释放特性。细胞毒性评估表明，空白的超分子胶束是无毒的，而载药的胶束显示出与游离DOX的抗癌活性相当的或什至更好的抗癌活性以及对癌细胞增殖的抑制作用。因此，开发的超分子组件可以潜在地用作药物控制释放载体。
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