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阿霉素偶联的 D-氨基葡萄糖和叶酸双功能化 InP/ZnS 量子点用于癌细胞成像和治疗。

Doxorubicin-conjugated D-glucosamine- and folate- bi-functionalised InP/ZnS quantum dots for cancer cells imaging and therapy.

机构信息

a Department of Materials Engineering , Science and Research Branch, Islamic Azad University , Tehran , Iran.

b Research Center for Pharmaceutical Nanotechnology , Biomedicine Institute, Tabriz University of Medical Sciences , Tabriz , Iran.

出版信息

J Drug Target. 2018 Mar;26(3):267-277. doi: 10.1080/1061186X.2017.1365876. Epub 2017 Aug 30.

Abstract

Nanoscaled quantum dots (QDs), with unique optical properties have been used for the development of theranostics. Here, InP/ZnS QDs were synthesised and functionalised with folate (QD-FA), D-glucosamine (QD-GA) or both (QD-FA-GA). The bi-functionalised QDs were further conjugated with doxorubicin (QD-FA-GA-DOX). Optimum Indium to fatty acid (In:MA) ratio was 1:3.5. Transmission electron microscopy (TEM) micrographs revealed spherical morphology for the QDs (11 nm). Energy-dispersive spectroscopy (EDS) spectrum confirmed the chemical composition of the QDs. MTT analysis in the OVCAR-3 cells treated with bare QDs, QD-FA, QD-GA, QD-FA-GA and QD-FA-GA-DOX (0.2 mg/mL of QDs) after 24 h indicated low toxicity for the bare QDs and functionalised QDs (about 80-90% cell viability). QD-FA-GA-DOX nanoparticles elicited toxicity in the cells. Cellular uptake of the engineered QDs were investigated in both folate receptor (FR)-positive OVCAR-3 cells and FR-negative A549 cells using fluorescence microscopy and FACS flow cytometry. The FA-functionalised QDs showed significantly higher uptake in the FR-positive OVCAR-3 cells, nonetheless the GA-functionalised QDs resulted in an indiscriminate uptake in both cell lines. In conclusion, our findings indicated that DOX-conjugated FA-armed QDs can be used as theranostics for simultaneous imaging and therapy of cancer.

摘要

纳米级量子点(QDs)具有独特的光学特性,已被用于治疗学的开发。在这里,合成了并功能化了具有叶酸(QD-FA)、D-葡糖胺(QD-GA)或两者(QD-FA-GA)的 InP/ZnS QDs。双功能化的 QDs 进一步与阿霉素(QD-FA-GA-DOX)缀合。最佳铟与脂肪酸(In:MA)的比例为 1:3.5。透射电子显微镜(TEM)照片显示 QDs 呈球形形态(11nm)。能量色散光谱(EDS)谱证实了 QDs 的化学组成。用 bare QDs、QD-FA、QD-GA、QD-FA-GA 和 QD-FA-GA-DOX(0.2mg/mL QDs)处理 OVCAR-3 细胞 24 小时后的 MTT 分析表明,bare QDs 和功能化 QDs 的毒性较低(约 80-90%的细胞活力)。QD-FA-GA-DOX 纳米粒子在细胞中引起毒性。使用荧光显微镜和 FACS 流式细胞术研究了工程化 QDs 在叶酸受体(FR)阳性 OVCAR-3 细胞和 FR 阴性 A549 细胞中的摄取情况。FA 功能化的 QDs 在 FR 阳性的 OVCAR-3 细胞中显示出明显更高的摄取率,然而,GA 功能化的 QDs 在两种细胞系中都导致了无差别摄取。总之,我们的研究结果表明,DOX 缀合的 FA 武装 QDs 可用作癌症的成像和治疗联合治疗的治疗剂。

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