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β-cyclodextrin based dual-responsive multifunctional nanotheranostics for cancer cell targeting and dual drug delivery
Carbohydrate Polymers ( IF 10.7 ) Pub Date : 2018-11-20 , DOI: 10.1016/j.carbpol.2018.11.049
Manita Das , Archana Solanki , Apeksha Joshi , Ranjitsinh Devkar , Sriram Seshadri , Sonal Thakore

Multifunctional nanoconjugates possessing an assortment of key functionalities such as magnetism, florescence, cell-targeting, pH and thermo-responsive features were developed for dual drug delivery. The novelty lies in careful conjugation of each of the functionality with magnetic Fe3O4 nanoparticles by virtue of urethane linkages instead of silica in a simple one pot synthesis. Further β-cyclodextrin (CD) was utilized to carry hydrophobic as well as hydrophilic drug. Superlative release of DOX could be obtained under acidic pH conditions and elevated temperature, which coincides with the tumor microenvironment. Mathematical modelling studies revealed that the drug release kinetics followed diffusion mechanism for both hydrophobic drug and hydrophilic drug. A number of fluorophores onto a single nanoparticle produced a strong fluorescence signal to optically track the nanoconjugates. Enhanced internalization due to folate specificity could be observed by fluorescence imaging. Further their accumulation driven by magnet near tumor site led to magnetic hyperthermia.

In vitro studies confirmed the nontoxicity and hemocompatibility of the nanoconjugates. Remarkable cell death was observed with drug-loaded nanoconjugates at very low concentrations in cancer cells. The internalization and cellular uptake of poor bioavailable anticancer agent curcumin were found to be remarkably enhanced on dosing the drug loaded nanoconjugates as compared to free curcumin. Site specific drug delivery due to folate conjugation and subsequent significant suppression in tumor growth was demonstrated by in vivo studies.



中文翻译:

基于β-环糊精的双反应多功能纳米治疗剂,可用于癌细胞靶向和双重药物递送

具有多种关键功能(例如磁性,荧光,靶向细胞,pH和热响应功能)的多功能纳米共轭物已开发用于双药物递送。新颖之处在于将每种功能与磁性Fe 3 O 4仔细结合在一起在一个简单的一锅合成中,借助氨基甲酸酯键代替二氧化硅形成了纳米颗粒。此外,β-环糊精(CD)用于携带疏水性和亲水性药物。在酸性pH条件和升高的温度下可以得到DOX的最高级释放,这与肿瘤的微环境相吻合。数学模型研究表明,对于疏水性药物和亲水性药物,药物释放动力学遵循扩散机理。单个纳米颗粒上的许多荧光团产生了很强的荧光信号,可以光学跟踪纳米共轭物。叶酸特异性导致的增强的内在化可以通过荧光成像观察到。此外,它们在肿瘤部位附近由磁体驱动的积累导致了磁热疗。

体外研究证实了纳米缀合物的无毒和血液相容性。在癌细胞中以非常低的浓度用载药纳米复合物观察到了显着的细胞死亡。发现与游离姜黄素相比,不良生物可利用的抗癌剂姜黄素的内在化和细胞摄取在给药载有药物的纳米缀合物上显着增强。通过体内研究证明,由于叶酸结合以及随后的肿瘤生长显着抑制,导致了特定部位的药物递送。

更新日期:2018-11-20
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