Bio-conjugated luminescent quantum dots of doped ZnS: a cyto-friendly system for targeted cancer imaging
Bio-conjugated luminescent quantum dots of doped ZnS: a cyto-friendly system for targeted cancer imaging
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DOI：
10.1088/0957-4484/20/6/065102
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发表时间：
2009-02-11
期刊：
影响因子：
3.5
通讯作者：
Nair, Shantikumar
中科院分区：
文献类型：
--
作者：
Manzoor, Koyakutty;Johny, Seby;Nair, Shantikumar
基于掺杂的硫化锌（ZnS）与癌症靶向配体叶酸（FA）缀合的无重金属发光量子点（QD）被提出作为用于靶向癌症成像的有希望的生物友好系统。采用简单的水溶液法在室温下制备了掺杂量子点。X射线衍射和透射电子显微镜研究表明，形成的单分散量子点的平均尺寸类似于4 nm的立方（闪锌矿）晶体结构。用金属（Al 3+）、过渡金属（Cu+、Mn 2+）和卤化物（F-）掺杂量子点导致多色发射，其中掺杂剂特定的颜色可调谐性范围从蓝色（480 nm）到红色（622 nm）。通过直接填充掺杂剂中心，可以使用生物友好的> 400 nm的可见光来激发掺杂QD中的发光中心，导致明亮的发射。使用正常肺成纤维细胞系（L929）、叶酸受体阳性（FR+）鼻咽表皮样癌细胞系（KB）和FR阴性（FR-）肺癌细胞系（A549）在体外测试裸和FA缀合的QD的细胞毒性。裸和FA-共轭ZnS量子点引起没有明显的毒性，即使在高浓度的类似100 μ M和48小时的孵育。相比之下，CdS量子点在相同的条件下制备显示出相对较高的毒性，即使在低浓度的类似0.1 μ M和24小时的孵育。FA-QD与不同细胞系的相互作用显示出在FR+癌细胞系中QD的高度特异性附着，而其他细胞系不受影响。量子点的明亮和稳定的发光可以用于成像单个癌细胞和癌细胞集落，而不影响它们的代谢活性和形态。因此，本研究首次提出了使用无毒的、无Cd-、Te-、Se-、Pb-和Hg-的发光量子点用于靶向癌症成像。
A heavy-metal-free luminescent quantum dot (QD) based on doped zinc sulfide (ZnS), conjugated with a cancer-targeting ligand, folic acid (FA), is presented as a promising bio-friendly system for targeted cancer imaging. Doped QDs were prepared by a simple aqueous method at room temperature. X-ray diffraction and transmission electron microscopy studies showed the formation of monodisperse QDs of average size similar to 4 nm with cubic (sphalerite) crystal structure. Doping of the QDs with metals (Al3+), transition metals (Cu+, Mn2+) and halides (F-) resulted in multi-color emission with dopant-specific color tunability ranging from blue (480 nm) to red (622 nm). Luminescent centers in doped QDs could be excited using bio-friendly visible light >400 nm by directly populating the dopant centers, leading to bright emission. The cytotoxicity of bare and FA conjugated QDs was tested in vitro using normal lung fibroblast cell line (L929), folate-receptor-positive (FR+) nasopharyngeal epidermoid carcinoma cell line (KB), and FR-negative (FR-) lung cancer cell line (A549). Both bare and FA-conjugated ZnS QDs elicited no apparent toxicity even at high concentrations of similar to 100 mu M and 48 h of incubation. In contrast, CdS QDs prepared under identical conditions showed relatively high toxicity even at low concentrations of similar to 0.1 mu M and 24 h of incubation. Interaction of FA-QDs with different cell lines showed highly specific attachment of QDs in the FR+ cancer cell line, leaving others unaffected. The bright and stable luminescence of the QDs could be used to image both single cancer cells and colonies of cancer cells without affecting their metabolic activity and morphology. Thus, this study presents, for the first time, the use of non-toxic, Cd-, Te-, Se-, Pb- and Hg-free luminescent QDs for targeted cancer imaging.