title: Cytotoxicity of quantum dots used for in vitro cellular labeling: role of QD surface ligand, delivery modality, cell type, and direct comparison to organic fluorophores.
abstract: Interest in taking advantage of the unique spectral properties of semiconductor quantum dots (QDs) has driven their widespread use in biological applications such as in vitro cellular labeling/imaging and sensing. Despite their demonstrated utility, concerns over the potential toxic effects of QD core materials on cellular proliferation and homeostasis have persisted, leaving in question the suitability of QDs as alternatives for more traditional fluorescent materials (e.g., organic dyes, fluorescent proteins) for in vitro cellular applications. Surprisingly, direct comparative studies examining the cytotoxic potential of QDs versus these more traditional cellular labeling fluorophores remain limited. Here, using CdSe/ZnS (core/shell) QDs as a prototypical assay material, we present a comprehensive study in which we characterize the influence of QD dose (concentration and incubation time), QD surface capping ligand, and delivery modality (peptide or cationic amphiphile transfection reagent) on cellular viability in three human cell lines representing various morphological lineages (epithelial, endothelial, monocytic). We further compare the effects of QD cellular labeling on cellular proliferation relative to those associated with a panel of traditionally employed organic cell labeling fluorophores that span a broad spectral range. Our results demonstrate the important role played by QD dose, capping ligand structure, and delivery agent in modulating cellular toxicity. Further, the results show that at the concentrations and time regimes required for robust QD-based cellular labeling, the impact of our in-house synthesized QD materials on cellular proliferation is comparable to that of six commercial cell labeling fluorophores. Cumulatively, our results demonstrate that the proper tuning of QD dose, surface ligand, and delivery modality can provide robust in vitro cell labeling reagents that exhibit minimal impact on cellular viability.
authors.affiliation: Center for Bio/Molecular Science and Engineering, Code 6900, and §Optical Sciences Division, Code 5600, U.S. Naval Research Laboratory , Washington, DC 20375, United States.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Bradburne
authors.forename: James B
authors.initials: JB
authors.lastname: Delehanty
authors.forename: Kelly
authors.initials: K
authors.lastname: Boeneman Gemmill
authors.forename: Bing C
authors.initials: BC
authors.lastname: Mei
authors.forename: Hedi
authors.initials: H
authors.lastname: Mattoussi
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Susumu
authors.forename: Juan B
authors.initials: JB
authors.lastname: Blanco-Canosa
authors.forename: Philip E
authors.initials: PE
authors.lastname: Dawson
authors.forename: Igor L
authors.initials: IL
authors.lastname: Medintz
mesh_terms: D019187:Cadmium Compounds / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005456:Fluorescent Dyes / Q000737:chemistry / Q000633:toxicity*; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D045663:Quantum Dots / Q000737:chemistry / Q000633:toxicity*; D018036:Selenium Compounds / Q000737:chemistry / Q000633:toxicity*; D013440:Sulfides / Q000737:chemistry / Q000633:toxicity*; D013501:Surface-Active Agents / Q000737:chemistry / Q000633:toxicity; D017967:Zinc Compounds / Q000737:chemistry / Q000633:toxicity*
chemical_list: D019187:Cadmium Compounds; D005456:Fluorescent Dyes; D008024:Ligands; D018036:Selenium Compounds; D013440:Sulfides; D013501:Surface-Active Agents; D017967:Zinc Compounds; C058667:cadmium selenide; C031238:zinc sulfide