Bio-conjugated luminescent quantum dots of doped ZnS: a cyto-friendly system fortargeted cancer imaging

Abstract

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 promisingbio-friendly system for targeted cancer imaging. Doped QDs were prepared by a simpleaqueous method at room temperature. X-ray diffraction and transmission electronmicroscopy studies showed the formation of monodisperse QDs of average size∼4 nm with cubic (sphalerite) crystal structure. Doping of the QDs with metals(Al3+), transitionmetals (Cu+, Mn2+) andhalides (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 vitrousing 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 ZnSQDs elicited no apparent toxicity even at high concentrations of∼100 µM and 48 h of incubation. In contrast, CdS QDs prepared under identicalconditions showed relatively high toxicity even at low concentrations of∼0.1 µM and 24 hof incubation. Interaction of FA–QDs with different cell lines showed highly specific attachment of QDsin the FR+ cancer cell line, leaving others unaffected. The bright and stable luminescence of the QDscould be used to image both single cancer cells and colonies of cancer cells withoutaffecting their metabolic activity and morphology. Thus, this study presents, for the firsttime, the use of non-toxic, Cd-, Te-, Se-, Pb- and Hg-free luminescent QDs for targetedcancer imaging.