Genotoxic capacity of Cd/Se semiconductor quantum dots with differing surface chemistries.
Quantum dots (QD) have unique electronic and optical properties promoting biotechnological advances. However, our understanding of the toxicological structure-activity relationships remains limited. This study aimed to determine the biological impact of varying nanomaterial surface chemistry by assessing the interaction of QD with either a negative (carboxyl), neutral (hexadecylamine; HDA) or positive (amine) polymer coating with human lymphoblastoid TK6 cells. Following QD physico-chemical characterisation, cellular uptake was quantified by optical and electron microscopy. Cytotoxicity was evaluated and genotoxicity was characterised using the micronucleus assay (gross chromosomal damage) and the HPRT forward mutation assay (point mutagenicity). Cellular damage mechanisms were also explored, focusing on oxidative stress and mitochondrial damage. Cell uptake, cytotoxicity and genotoxicity were found to be dependent on QD surface chemistry. Carboxyl-QD demonstrated the smallest agglomerate size and greatest cellular uptake, which correlated with a dose dependent increase in cytotoxicity and genotoxicity. Amine-QD induced minimal cellular damage, while HDA-QD promoted substantial induction of cell death and genotoxicity. However, HDA-QD were not internalised by the cells and the damage they caused was most likely due to free cadmium release caused by QD dissolution. Oxidative stress and induced mitochondrial reactive oxygen species were only partially associated with cytotoxicity and genotoxicity induced by the QD, hence were not the only mechanisms of importance. Colloidal stability, nanoparticle (NP) surface chemistry, cellular uptake levels and the intrinsic characteristics of the NPs are therefore critical parameters impacting genotoxicity induced by QD.
Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Biomedical NMR Unit-MoSAIC, Department of Medicine, KU Leuven, B-3000 Leuven, Belgium and.
Bella B
BB
Manshian
Biomedical NMR Unit-MoSAIC, Department of Medicine, KU Leuven, B-3000 Leuven, Belgium and.
Stefaan J
SJ
Soenen
Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK.
Andy
A
Brown
Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK.
Nicole
N
Hondow
Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
John
J
Wills
Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
Gareth J S
GJ
Jenkins
Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, s.h.doak@swansea.ac.uk.
Shareen H
SH
Doak
D002104:Cadmium / Q000494:pharmacology; D002460:Cell Line; D004249:DNA Damage; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D018384:Oxidative Stress; D045663:Quantum Dots / Q000737:chemistry / Q000633:toxicity*; D012643:Selenium / Q000494:pharmacology; D012666:Semiconductors; D013329:Structure-Activity Relationship; D013499:Surface Properties
D009153:Mutagens; D002104:Cadmium; D012643:Selenium