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氧化石墨烯量子点-壳聚糖纳米诊疗一体化平台作为一种 pH 响应载体提高姜黄素摄取内化:体外与计算研究。

Graphene oxide quantum dot-chitosan nanotheranostic platform as a pH-responsive carrier for improving curcumin uptake internalization: In vitro & in silico study.

机构信息

Biosensor Research Center (BRC), School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Biomater Adv. 2022 Aug;139:213017. doi: 10.1016/j.bioadv.2022.213017. Epub 2022 Jul 6.

Abstract

We herein fabricated a cancer nanotheranostics platform based on Graphene Oxide Quantum Dot-Chitosan-polyethylene glycol nanoconjugate (GOQD-CS-PEG), which were targeted with MUC-1 aptamer towards breast and colon tumors. The interaction between aptamer and MUC-1 receptor on the desired cells was investigated utilizing molecular docking. The process of curcumin release was investigated, as well as the potential of the produced nanocomposite in targeted drug delivery, specific detection, and photoluminescence imaging. The fluorescence intensity of GOQD-CS-PEG was reduced due to transferred energy between (cytosine-guanin) base pairs in the hairpin structure of the aptamer, resulting in an "on/off" photoluminescence bio-sensing. Interestingly, the integration of pH-responsive chitosan nanoparticles in the nanocomposite results in a smart nanocomposite capable of delivering more curcumin to desired tumor cells. When selectively binds to the MUC-1 receptor, the two strands of aptamer separate in acidic conditions, resulting in a sustained drug release and photoluminescence recovery. The cytotoxicity results also revealed that the nanocomposite was more toxic to MUC-1-overexpressed tumor cells than to negative control cell lines, confirming its selective targeting. As a result, the proposed nanocomposite could be used as an intelligent cancer nanotheranostic platform for tracing MUC-1-overexpressed tumor cells and targeting them with great efficiency and selectivity.

摘要

我们在此基于石墨烯量子点-壳聚糖-聚乙二醇纳米复合物(GOQD-CS-PEG)构建了一种癌症纳米治疗平台,该平台通过 MUC-1 适体靶向乳腺癌和结肠癌肿瘤。利用分子对接研究了适体与所需细胞上 MUC-1 受体的相互作用。研究了姜黄素的释放过程,以及所制备的纳米复合材料在靶向药物传递、特异性检测和光致发光成像中的潜力。GOQD-CS-PEG 的荧光强度由于适体发夹结构中(胞嘧啶-鸟嘌呤)碱基对之间的能量转移而降低,导致“开/关”光致发光生物传感。有趣的是,将 pH 响应性壳聚糖纳米颗粒整合到纳米复合物中会产生一种智能纳米复合物,能够将更多的姜黄素递送到所需的肿瘤细胞中。当选择性地与 MUC-1 受体结合时,适体的两条链在酸性条件下分离,导致药物持续释放和光致发光恢复。细胞毒性结果还表明,与阴性对照细胞系相比,纳米复合物对过表达 MUC-1 的肿瘤细胞更具毒性,证实了其选择性靶向。因此,所提出的纳米复合物可用作一种智能癌症纳米治疗平台,用于追踪过表达 MUC-1 的肿瘤细胞,并具有高效和选择性的靶向作用。

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