title: The performance of gradient alloy quantum dots in cell labeling.
abstract: The interest in using quantum dots (QDots) as highly fluorescent and photostable nanoparticles in biomedicine is vastly increasing. One major hurdle that slows down the (pre)clinical translation of QDots is their potential toxicity. Several strategies have been employed to optimize common core-shell QDots, such as the use of gradient alloy (GA)-QDots. These particles no longer have a size-dependent emission wavelength, but the emission rather depends on the chemical composition of the gradient layer. Therefore, particles of identical sizes but with emission maxima spanning the entire visible spectrum can be generated. In the present study, two types of GA-QDots are studied with respect to their cytotoxicity and cellular uptake. A multiparametric cytotoxicity approach reveals concentration-dependent effects on cell viability, oxidative stress, cell morphology and cell functionality (stem cell differentiation and neurite outgrowth), where the particles are very robust against environmentally-induced breakdown. Non-toxic concentrations are defined and compared to common core-shell QDots analyzed under identical conditions. Additionally, this value is translated into a functional value by analyzing the potential of the particles for cell visualization. Interestingly, these particles result in clear endosomal localization, where different particles result in identical intracellular distributions. This is in contrast with CdTe QDots with the same surface coating, which resulted in clearly distinct intracellular distributions as a result of differences in nanoparticle diameter. The GA-QDots are therefore ideal platforms for cell labeling studies given their high brightness, low cytotoxicity and identical sizes, resulting in highly similar intracellular particle distributions which offer a lot of potential for optimizing drug delivery strategies.
authors.affiliation: MoSAIC/Biomedical NMR Unit, Department of Medicine, Catholic University of Leuven, B3000 Leuven, Belgium. Electronic address: Stefaan.Soenen@med.kuleuven.be.
authors.forename: Stefaan J
authors.initials: SJ
authors.lastname: Soenen
authors.affiliation: MoSAIC/Biomedical NMR Unit, Department of Medicine, Catholic University of Leuven, B3000 Leuven, Belgium.
authors.forename: Bella B
authors.initials: BB
authors.lastname: Manshian
authors.affiliation: MoSAIC/Biomedical NMR Unit, Department of Medicine, Catholic University of Leuven, B3000 Leuven, Belgium.
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.affiliation: Lab General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, University of Gent, B9000 Gent, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Demeester
authors.affiliation: Lab General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, University of Gent, B9000 Gent, Belgium; Center for Nano- and Biophotonics, Faculty of Pharmaceutical Sciences, University of Gent, B9000 Gent, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Braeckmans
authors.affiliation: Lab General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, University of Gent, B9000 Gent, Belgium. Electronic address: Stefaan.DeSmedt@ugent.be.
authors.forename: Stefaan C
authors.initials: SC
authors.lastname: De Smedt
mesh_terms: D000497:Alloys / Q000032:analysis* / Q000378:metabolism / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005456:Fluorescent Dyes / Q000032:analysis* / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D018384:Oxidative Stress / Q000187:drug effects; D045663:Quantum Dots / Q000032:analysis* / Q000378:metabolism / Q000633:toxicity; D013194:Staining and Labeling / Q000379:methods
chemical_list: D000497:Alloys; D005456:Fluorescent Dyes
keywords: Cell labeling; Fluorescence; Gradient alloy quantum dots; Nanoparticle; Nanotoxicology