Journal Article

The role of intracellular trafficking of CdSe/ZnS QDs on their consequent toxicity profile

Parak, Wolfgang J., Himmelreich, Uwe, Martens, Thomas F., Braeckmans, Kevin, Demeester, Jo, Doak, Shareen H., De Smedt, Stefaan C., Manshian, Bella B., Jenkins, Gareth J. S., Pelaz, Beatriz, Soenen, Stefaan J., Kantner, Karsten

2017

Overview

Background Nanoparticle interactions with cellular membranes and the kinetics of their transport and localization are important determinants of their functionality and their biological consequences. Understanding these phenomena is fundamental for the translation of such NPs from in vitro to in vivo systems for bioimaging and medical applications. Two CdSe/ZnS quantum dots (QD) with differing surface functionality (NH 2 or COOH moieties) were used here for investigating the intracellular uptake and transport kinetics of these QDs. Results In water, the COOH- and NH 2 -QDs were negatively and positively charged, respectively, while in serum-containing medium the NH 2 -QDs were agglomerated, whereas the COOH-QDs remained dispersed. Though intracellular levels of NH 2 - and COOH-QDs were very similar after 24 h exposure, COOH-QDs appeared to be continuously internalised and transported by endosomes and lysosomes, while NH 2 -QDs mainly remained in the lysosomes. The results of (intra)cellular QD trafficking were correlated to their toxicity profiles investigating levels of reactive oxygen species (ROS), mitochondrial ROS, autophagy, changes to cellular morphology and alterations in genes involved in cellular stress, toxicity and cytoskeletal integrity. The continuous flux of COOH-QDs perhaps explains their higher toxicity compared to the NH 2 -QDs, mainly resulting in mitochondrial ROS and cytoskeletal remodelling which are phenomena that occur early during cellular exposure. Conclusions Together, these data reveal that although cellular QD levels were similar after 24 h, differences in the nature and extent of their cellular trafficking resulted in differences in consequent gene alterations and toxicological effects.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Autophagy - drug effects / Biocompatibility / Biotechnology / Cadmium Compounds - analysis / Cadmium Compounds - metabolism / Cadmium Compounds - toxicity / Cadmium selenide / Cadmium selenides / Cancer / Cell Line / Cell membranes / Chemical properties / Chemistry / Chemistry and Materials Science / Cytoskeleton / Embryos / Endosomal uptake / Endosomes / Exposure / Gene alterations / Gene expression / Gene Expression Regulation - drug effects / Homeostasis / Humans / Hypoxia / Intracellular / Intracellular levels / Intracellular localization / Kinetics / Localization / Lysosomes / Lysosomes - drug effects / Lysosomes - metabolism / Medical imaging / Membranes / Microscopy / Mitochondria / Mitochondria - drug effects / Mitochondria - metabolism / Molecular Medicine / Nanomaterials / Nanoparticles / Nanotechnology / Nanotoxicity / Phagocytosis / Quantum dot NPs / Quantum dots / Quantum Dots - analysis / Quantum Dots - metabolism / Quantum Dots - toxicity / Reactive oxygen species / Reactive Oxygen Species - metabolism / Selenium Compounds - analysis / Selenium Compounds - metabolism / Selenium Compounds - toxicity / Studies / Sulfides - analysis / Sulfides - metabolism / Sulfides - toxicity / Toxicity / Zinc compounds / Zinc Compounds - analysis / Zinc Compounds - metabolism / Zinc Compounds - toxicity / Zinc sulfide