title: Coating of Quantum Dots strongly defines their effect on lysosomal health and autophagy.
abstract: In the last decade the interest in autophagy got an incredible boost and the phenomenon quickly turned into an extensive research field. Interestingly, dysfunction of this cytoplasmic clearance system has been proposed to lie at the root of multiple diseases including cancer. We therefore consider it crucial from a toxicological point of view to investigate if nanomaterials that are developed for biomedical applications interfere with this cellular process. Here, we study the highly promising 'gradient alloyed' Quantum Dots (QDs) that differ from conventional ones by their gradient core composition which allows for better fluorescent properties. We carefully examined the toxicity of two identical gradient alloyed QDs, differing only in their surface coatings, namely 3-mercaptopropionic (MPA) acid and polyethylene glycol (PEG). Next to more conventional toxicological endpoints like cytotoxicity and oxidative stress, we examined the influence of these QDs on the autophagy pathway. Our study shows that the cellular effects induced by QDs on HeLa cells were strongly dictated by the surface coat of the otherwise identical particles. MPA-coated QDs proved to be highly biocompatible as a result of lysosomal activation and ROS reduction, two cellular responses that help the cell to cope with nanomaterial-induced stress. In contrast, PEGylated QDs were significantly more toxic due to increased ROS production and lysosomal impairment. This impairment next results in autophagy dysfunction which likely adds to their toxic effects. Taken together, our study shows that coating QDs with MPA is a better strategy than PEGylation for long term cell tracking with minimal cytotoxicity.
  
  
  
  Gradient alloyed Quantum Dots (GA-QDs) are highly promising nanomaterials for biomedical imaging seeing they exhibit supremely fluorescent properties over conventional QDs. The translation of these novel QDs to the clinic requires a detailed toxicological examination, though the data on this is very limited. We therefore applied a systematic approach to examine the toxicity of GA-QDs coated with two commonly applied surface ligands, this while focusing on the autophagy pathway. The impact of QDs on this pathway is of importance since it has been connected with various diseases, including cancer. Our data accentuates that the coating defines the impact on autophagy and therefore the toxicity induced by QDs on cells: while MPA coated QDs were highly biocompatible, PEGylated QDs were toxic.
authors.affiliation: Lab of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B9000 Ghent, Belgium; Ghent Research Group on Nanomedicines, Ghent University, Ottergemsesteenweg 460, B9000 Ghent, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Peynshaert
authors.affiliation: Biomedical MRI Unit/MoSAIC, Department of Imaging and Pathology, Catholic University of Leuven, Faculty of Medicine, UZ Herestraat 49 Box 7003, B3000 Leuven, Belgium.
authors.forename: Stefaan J
authors.initials: SJ
authors.lastname: Soenen
authors.affiliation: Biomedical MRI Unit/MoSAIC, Department of Imaging and Pathology, Catholic University of Leuven, Faculty of Medicine, UZ Herestraat 49 Box 7003, B3000 Leuven, Belgium.
authors.forename: Bella B
authors.initials: BB
authors.lastname: Manshian
authors.affiliation: Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, Wales, United Kingdom.
authors.forename: Shareen H
authors.initials: SH
authors.lastname: Doak
authors.affiliation: Lab of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B9000 Ghent, Belgium; Centre for Nano- and Biophotonics, Ghent University, B9000 Ghent, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Braeckmans
authors.affiliation: Lab of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B9000 Ghent, Belgium; Ghent Research Group on Nanomedicines, Ghent University, Ottergemsesteenweg 460, B9000 Ghent, Belgium. Electronic address: Stefaan.Desmedt@ugent.be.
authors.forename: Stefaan C
authors.initials: SC
authors.lastname: De Smedt
authors.affiliation: Lab of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B9000 Ghent, Belgium; Ghent Research Group on Nanomedicines, Ghent University, Ottergemsesteenweg 460, B9000 Ghent, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Remaut
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D045663:Quantum Dots / Q000737:chemistry* / Q000633:toxicity; D055672:Static Electricity
chemical_list: D015415:Biomarkers; D020099:Coated Materials, Biocompatible
keywords: Autophagy; Biocompatibility; Lysosome; Quantum Dot