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

Abstract

The purpose of the presented work was to modify the surface of core/shell-type CdSe x S 1-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.

Design, fabrication and evaluation of amphiphilic hyaluronic acid conjugates as efficient carriers of 6‐thioguanine for in vitro anticancer drug delivery applications

“…The pH of the resulting solution was maintained at 10-11 by adding sodium hydroxide (pH monitored by pH paper) due to higher solubility of TG in basic conditions. 45 The solution was stirred vigorously for 1 h and left overnight. Then the solution was subjected to dialysis (MWCO of 1000 Da) against water (4 × 6 h) to eliminate free TG.…”

Advances in Thiopurine Drug Delivery: The Current State-of-the-Art

“…6-MP was more easily released from 6-MPCs at pH 7.4 than at pH 4.8 because of its higher solubility in an alkaline environment. Cmax is 478.2 ng/ml at 0.5 h, AUC 558.7 mg/l∙h, T 1/2 is 1.5 h. Survival time (days of 51, 23.5 and 22.5 days for MP NP vs MP vs PBS solution Grabowska-Jadach [ 120 ] Poland Nanoparticles TG CdSexS1−x/ZnS quantum dots In vitro (A549, MRC5 and K562 cells) ↑Cytotoxicity of CdSexS1−x/ZnS–6-TG compared to TG (Fig. 4 in the article by Jadach et al [ 120 ]) Sierpe [ 67 ] Chile Nanoparticles TG/MP Au and βcyclodextrins In vitro This paper describes the synthesis, characterization and permeability of the nanoparticles Aghevlian [ 75 ] Iran Nanoparticles TG Au In vitro (MCF-7 cells) ↑ Cytotoxicity for TG-NPs compared to TG ( P < 0.001) (see Fig.…”

“…Cmax is 478.2 ng/ml at 0.5 h, AUC 558.7 mg/l∙h, T 1/2 is 1.5 h. Survival time (days of 51, 23.5 and 22.5 days for MP NP vs MP vs PBS solution Grabowska-Jadach [ 120 ] Poland Nanoparticles TG CdSexS1−x/ZnS quantum dots In vitro (A549, MRC5 and K562 cells) ↑Cytotoxicity of CdSexS1−x/ZnS–6-TG compared to TG (Fig. 4 in the article by Jadach et al [ 120 ]) Sierpe [ 67 ] Chile Nanoparticles TG/MP Au and βcyclodextrins In vitro This paper describes the synthesis, characterization and permeability of the nanoparticles Aghevlian [ 75 ] Iran Nanoparticles TG Au In vitro (MCF-7 cells) ↑ Cytotoxicity for TG-NPs compared to TG ( P < 0.001) (see Fig. 5 in the article by Aghevlian et al) Dorniani [ 76 ] Malaysia Nanoparticles MP Magnetite + chitosan In vitro (WEHI-3 cells) 93.2% and 50.6 release at pH 4.8 and 7.4, similar cytotoxicity of NPs compared to MP Sleightholm [ 77 ] US Nanoparticles TG Au In vitro This paper describes the synthesis and characterization of the nanoparticles Podsiadlo [ 96 ] US Nanoparticles MP Au In vitro (K562 cells) Au-NPs > MP inhibition of K-562 leukemic cells NP nanoparticles, HA hyaluronic acid, PC phosphatidyl choline, PEG polyethylene glycol, ...…”

Nanotechnology enabled management approaches against the Covid-19 pandemic

“…Polyvinyl alcohol (PVA)coated magnetite nanoparticles were reported as ideal nanocarrier for the sustained release and targeted delivery of 6-MP with lower therapeutic dose and lower side effects [92]. Moreover, CdSe/ZnS coreshell quantum dots offer triple advantages of being an efficient carrier for 6-TG and a tracking tool owing to its fluorescence, a suppressor of adverse drug properties resulting from the presence of thione group in the 6-TG structure [93]. Disulphide-based polyethyeneglycol (PEG)conjugated nanogels of 60 nm were used to entrap 6-Methylguanine with high pay load and stimuli-responsive release property [94].…”