Chemical Engineering Journal ( IF 13.3 ) Pub Date : 2020-02-15 , DOI: 10.1016/j.cej.2020.124468 Qiaojuan Jia , Zhenzhen Li , Chuanpan Guo , Xiaoyu Huang , Mengmeng Kang , Yingpan Song , Linghao He , Nan Zhou , Minghua Wang , Zhihong Zhang , Guodong Fu , Miao Du
A novel drug nanocarrier system based on bimetallic NiCo Prussian blue analogue (NiCo-PBA) was constructed for targeted anticancer drug delivery and cancer therapy. Rare earth Tb3+ ion was doped in NiCo-PBA to prepare a complex with strong fluorescence performance (represented by [email protected]3+). The [email protected]3+ complex was functionalized with poly(ethyleneglycol)- dimethacrylate (PEGMA) (represented by [email protected]3+@PEGMA) by the surface initiated atom transfer radical polymerization to enhance its aqueous stability, pH-responsive capability, and good biocompatibility, thus improving the drug-loading efficiency of NiCo-PBA. An aptamer ligand (AS1411) targeting nucleolin was insensitively anchored onto the [email protected]3+@PEGMA surface for specifically recognizing breast cancer cells. Therefore, the functionalization of [email protected]3+@PEGMA with AS1411 (denoted by [email protected]3+@[email protected]) allowed the pH-responsive drug release within cancer cells and enhanced the tumor-targeted delivery of doxorubicin (DOX). Confocal fluorescence imaging revealed that the [email protected]3+@[email protected] composite was mainly located in the cytoplasm after cellular internalization, and released DOX within the cytoplasm. The in vivo antitumor study with tumor-bearing mice illustrated that [email protected]3+@[email protected]@DOX considerably accumulated in tumor tissues. The tumor growth can be effectively suppressed and exhibited enhanced an anticancer activity in vivo. The proposed [email protected]3+@[email protected] composite represents a growing potential for effective DOX delivery and targeted therapy in vitro and in vivo. The present work can extend the application of PBAs in cancer therapy and cell imaging and provides a new strategy for the construction of controlled release system of anticancer drugs.
中文翻译:
掺有Tb(III)离子的PEGMA修饰的双金属NiCo普鲁士蓝类似物:有效的pH响应和控释系统,用于抗癌药物
基于双金属NiCo普鲁士蓝类似物(NiCo-PBA)的新型药物纳米载体系统被构建用于靶向的抗癌药物递送和癌症治疗。在NiCo-PBA中掺杂稀土Tb 3+离子,以制备具有强荧光性能的复合物(以[email protected] 3+表示)。[电子邮件保护的] 3+复合物用聚(乙二醇)-二甲基丙烯酸酯(PEGMA)官能化(由[电子邮件保护的] 3+代表通过表面引发的原子转移自由基聚合反应来增强其水稳定性,pH响应能力和良好的生物相容性,从而提高NiCo-PBA的载药效率。靶向核仁素的适体配体(AS1411)不敏感地锚定在[电子邮件保护的] 3+ @PEGMA表面上,用于特异性识别乳腺癌细胞。因此,具有AS1411的[电子邮件保护的] 3+ @PEGMA的功能化(以[电子邮件保护的] 3+ @ [电子邮件保护的]表示)允许pH响应药物在癌细胞内释放,并增强了肿瘤靶向性的阿霉素( DOX)。共聚焦荧光成像显示[电子邮件保护] 3+@ [受电子邮件保护的]复合材料在细胞内化后主要位于细胞质中,并在细胞质内释放DOX。对荷瘤小鼠的体内抗肿瘤研究表明,[电子邮件保护的] 3+ @ [电子邮件保护的] @DOX在肿瘤组织中大量积累。肿瘤的生长可以被有效地抑制,并在体内表现出增强的抗癌活性。拟议中的[受电子邮件保护的] 3+ @ [受电子邮件保护的]复合材料代表了有效的DOX递送和体外和体内靶向治疗的潜力。目前的工作可以扩展PBA在癌症治疗和细胞成像中的应用,并为构建抗癌药物控释系统提供新的策略。