Bioelectric and Morphological Response of Liquid-Covered Human Airway Epithelial Calu-3 Cell Monolayer to Periodic Deposition of Colloidal 3-Mercaptopropionic-Acid Coated CdSe-CdS/ZnS Core-Multishell Quantum Dots

Abstract

Lung epithelial cells are extensively exposed to nanoparticles present in the modern urban environment. Nanoparticles, including colloidal quantum dots (QDs), are also considered to be potentially useful carriers for the delivery of drugs into the body. It is therefore important to understand the ways of distribution and the effects of the various types of nanoparticles in the lung epithelium. We use a model system of liquid-covered human airway epithelial Calu-3 cell cultures to study the immediate and long-term effects of repeated deposition of colloidal 3-mercaptopropionic-acid coated CdSe-CdS/ZnS core-multishell QDs on the lung epithelial cell surface. By live confocal microscope imaging and by QD fluorescence measurements we show that the QD permeation through the mature epithelial monolayers is very limited. At the time of QD deposition, the transepithelial electrical resistance (TEER) of the epithelial monolayers transiently decreased, with the decrement being proportional to the QD dose. Repeated QD deposition, once every six days for two months, lead to accumulation of only small amounts of the QDs in the cell monolayer. However, it did not induce any noticeable changes in the long-term TEER and the molecular morphology of the cells. The colloidal 3-mercaptopropionic-acid coated CdSe-CdS/ZnS core-multishell QDs could therefore be potentially used for the delivery of drugs intended for the surface of the lung epithelia during limited treatment periods.

Transport and release of colloidal 3-mercaptopropionic acid-coated CdSe–CdS/ZnS core-multishell quantum dots in human umbilical vein endothelial cells

“…The first important finding is that 3MPA-QDs became internalized by HUVECs in an active way starting after 2 h incubation with 3MPA-QDs, but strikingly, they were released from the cells after 48 h. The cellular uptake/ release, the lack of cytotoxicity and previously reported unaffected cell proliferation 24 can be attributed to the unique surface chemistry of the 3MPA-QDs. Usually, nanoparticles that enter the cell through endocytosis are delivered to the lysosomes 34,35 where they can be degraded by lysosomal lytic enzymes.…”

“…[22][23][24] Since material properties of colloidal QDs are strongly related to QD's synthesis method, we described first the synthesis of our 3MPA-QDs consisting of three major steps. 1) The first step was to synthesize CdSe cores.…”

“…As one of the well-characterized vascular endothelial cells, human umbilical vein endothelial cells (HUVECs) express the typical endothelial phenotype and are often used in studying nanomaterial toxicity. [18][19][20][21] In this article, we investigated 3-mercaptopropionic acid-coated CdSe-CdS/ZnS core-multishell quantum dots (3MPA-QDs) obtained by surface ligand exchange of asgrown octadecylamine-coated quantum dots (ODA-QDs) [22][23][24] and exploited their transport, release and photophysical properties in HUVECs. We found that the variation of QD optical properties could be used as a fingerprint to accurately discriminate their spatial locations in intracellular compartments.…”

Quantum dots modulate intracellular Ca²⁺ level in lung epithelial cells

“…9 TEER is generally known to be an indicator of the integrity of tight junctions, reflecting the ionic conductance of the paracellular pathway in the epithelial layer. 10 The reported QD-induced transient TEER decrease may, therefore, indicate a loosening of the tight junctions.…”

“…However, no detectable morphological modifications were found in Calu-3 epithelial layers after repeated QD depositions, once per 6 days for 60 days. 9 Cytoplasmic Ca 2+ concentration [Ca 2+ ] i plays a key role in a variety of cellular functions and is a master regulator of airway physiology. It controls fluid, mucus, and antimicrobial peptide secretion, ciliary beating, and smooth muscle contraction.…”