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用于靶向生长抑素受体的生长抑素修饰量子点

Somatostatin Decorated Quantum Dots for Targeting of Somatostatin Receptors.

作者信息

Hafez Abdellatif Ahmed Abdelfattah, Abdelhafez Wael Abdellah, Sarhan Hatem Abdelmunsef

机构信息

Department of Pharmaceutics and Industrial pharmacy, Faculty of Pharmacy, Al-Azhar University, Assuit, Egypt.

Department of Pharmaceutics and Industrial pharmacy, Faculty of Pharmacy, El-Minia University, El-Minia, Egypt.

出版信息

Iran J Pharm Res. 2018 Spring;17(2):513-524.

Abstract

Due to the unique optical properties like high brightness and narrow emission bands of Quantum dots, it is used as simple fluorescence materials in bio-imaging, immunoassays, microarrays, and other applications. To easy invistigate cell lines that overexpressed somtostatin receptors, somatostatin (SST) was conjugated with Quantum dots carrying PEG amine (Qdots-PEG-NH). The conjugation of SST to Qdots-PEG-NH started with the thiolation of SST using Traut's reagent. Moreover, the Qdots-PEG-NH were subsequently activated by 500-fold molar excess of sulfosuccinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo-SMCC) dissolved in phosphate buffer. The Qdots-PEG-NH-sulfo-SMCC was conjugated to the thiolated-SST to form Qdots-SST. The number of sulfhydryl groups can be controlled by the molar ratio of Traut´s reagent to SST. Thiolation was necessary for the conjugation of SST to Qdots-PEG-NH. This was achieved by reacting the SST with Traut's reagent in a 1:1 molar ratio. Ellman's reagent was used to determine the number of sulfhydryle groups. Furthermore, cellular uptake study on triple negative breast cancer cells (HCC-1806) showed that the numbers of Qdots-SST per cell were significantly higher compared to unmodified Qdots-PEG-NH when quantified using inductively coupled plasma optical emission spectroscopy (ICP-OES). Moreover, the binding of Qdots-SST to cells can be suppressed by addition of free SST, indicating that the binding of Qdots-SST to cells is due to receptor-specific binding.

摘要

由于量子点具有高亮度和窄发射带等独特的光学特性,它被用作生物成像、免疫测定、微阵列及其他应用中的简单荧光材料。为了便于研究过表达生长抑素受体的细胞系,将生长抑素(SST)与携带聚乙二醇胺的量子点(Qdots-PEG-NH)偶联。SST与Qdots-PEG-NH的偶联始于使用特劳特试剂对SST进行硫醇化。此外,随后用溶解在磷酸盐缓冲液中的500倍摩尔过量的磺基琥珀酰亚胺4-(N-马来酰亚胺甲基)环己烷-1-羧酸盐(磺基-SMCC)激活Qdots-PEG-NH。将Qdots-PEG-NH-磺基-SMCC与硫醇化的SST偶联以形成Qdots-SST。巯基的数量可以通过特劳特试剂与SST的摩尔比来控制。硫醇化对于SST与Qdots-PEG-NH的偶联是必要的。这通过使SST与特劳特试剂以1:1的摩尔比反应来实现。使用埃尔曼试剂来确定巯基的数量。此外,对三阴性乳腺癌细胞(HCC-1806)的细胞摄取研究表明,当使用电感耦合等离子体发射光谱法(ICP-OES)进行定量时,每个细胞中Qdots-SST的数量比未修饰的Qdots-PEG-NH显著更高。此外,添加游离SST可以抑制Qdots-SST与细胞的结合,表明Qdots-SST与细胞的结合是由于受体特异性结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d31/5985169/7adaaa399e58/ijpr-17-513-g001.jpg

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