Modification of fluorescent nanocrystals with 6-thioguanine: monitoring of drug delivery

Ilona Grabowska-Jadach,Dominika Kulpińska,Klaudia Komendacka,Mariusz Pietrzak,Marcin Drozd

doi:10.1007/s13204-019-01101-6

Ilona Grabowska-Jadach, Dominika Kulpińska + Show 3 more

Open Access

https://doi.org/10.1007/s13204-019-01101-6

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Journal: Applied nanoscience	Publication Date: Jul 11, 2019
Citations: 10	License type: open-access

Affiliation: Warsaw University of Technology

Abstract

The purpose of the presented work was to modify the surface of core/shell-type CdSexS1–x/ZnS quantum dots (QDs) with an anticancer drug to form bifunctional nanoconjugate for imaging and drug delivery. 6-Thioguanine (6-TG) which is used to treat acute myeloid and lymphoblastic leukemia was applied for this aim. The modification of the nanocrystals was carried out using a biphasic method, based on transferring of QDs from the organic phase to the aqueous one with the simultaneous exchange of hydrophobic ligand to the hydrophilic one. To enable a complex evaluation of 6-TG bioactivity, the surface of quantum dots was also modified using mercaptoacetic acid (MAA). Mercaptoacetic acid was chosen as a biologically neutral ligand; so, it was possible to evaluate the effect of nanocrystals toxicity without the participation of the drug (6-TG ligand versus neutral ligand). Moreover, the effect of 6-TG itself on cells was also studied. The studies were carried out on three cell lines: K562 (human myeloid leukemia), A549 (human lung cancer cells) and MRC-5 (normal human lung cells). Evaluation of the cytotoxicity of nanostructures, at various concentrations, was carried out after 24- and 48-h incubation of the cell culture with nanoparticles/drug solutions. MTT and the Alamar Blue assays were used to determine cell viability. Based on the cytotoxicity measurements, it was found that quantum dots modified with 6-TG are more toxic than the drug itself or QDs modified with 3-mercaptoacetic acid. Images taken using fluorescence and confocal microscopy allowed to define the location of examined QDs inside cells.

Highlights

Quantum dots (QDs) are inorganic semiconductor nanocrystals, consisting of 100–1000 of atoms belonging typically to groups II and VI or III and V (e.g. InP, InAs) of the periodic table (e.g. CdSe, CdTe) (Zrazhevskiy et al 2010)
CdSexS1–x mixed-core-type nanocrystals coated with ZnS and stabilized with oleic acid (6-nm diameter, solution in toluene, λem = 630 nm) were purchased from Cytodiagnostics (Burlington, Canada). 6-thioguanine and mercaptoacetic acid were purchased from Sigma Merck (Poznań, Poland)
The attractiveness of 6-TG as a drug in a combination with the possibility to use it as QDs surface modifier prompted us to demonstrate for the first time 6-TG-functionalized CdSeS/ ZnS quantum dots as a promising tool for theranostics

Summary

Introduction

Quantum dots (QDs) are inorganic semiconductor nanocrystals, consisting of 100–1000 of atoms belonging typically to groups II and VI or III and V (e.g. InP, InAs) of the periodic table (e.g. CdSe, CdTe) (Zrazhevskiy et al 2010). They are typically characterized with a diameter between 2 and 10 nm, which is close to the exciton Bohr radius (electron–hole distance). The applied ligands often determine the applicability of these nanoparticles; for instance for biological or medical purposes, the ligands have to be carefully selected (Abbasi et al 2015; Azzazy et al 2007; Smith et al 2008)

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