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Amine-functionalized graphene quantum dots–hyaluronic acid nanocomposite as a high-resolution cancer cell bioimaging and biosensing system

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Abstract

Cancer-related deaths are rising every day due to the lack of efficient detection methods in the primary stages, especially before metastasis, which is the main reason for the uncontrollability of cancer. Thus, a novel method is urgently required to efficiently and accurately identify circulating cancer cells scattered in the blood of patients with the primary stages of cancer. Here, in this work, a new fluorescent biosensor based on amine-functionalized graphene quantum dot (af-GQD) was constructed through a hydrothermal method from graphene oxide. Afterward, af-GQD was grafted with HA (GQD-HA) for specific detection through a ligand–receptor concept in which HA recognizes CD44 receptors, which are overexpressed on certain cancer cells such as A549, MDA-MB-231, MCF-7, and HeLa. Then, the intensity of fluorescent signals detected from each cell line media was assessed and quantified. Besides, the designed nanocomposite can be used as a bioimaging agent due to its remarkable properties, such as high fluorescent emission, good compatibility, low cytotoxicity, high resistance to photobleaching, and chemical stability. The results indicated that the designed nanocomposite could act either as an efficient a bioimaging agent or as a biosensor with high specificity and sensitivity with a linear detection range from 500 to 5000 cells/ml for the detection of CTCs. The limit of detection for cell lines was 95, 98, 112, 123 cell/ml for MDA-MB-231, A549, MCF-7, and HeLa, respectively.

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Data Availability

All data generated or analysed during this study are included in this published article

Abbreviations

CTC:

Circulating tumor cell

DI:

Deionized

DLS:

Dynamic light scattering

DMEM:

Dulbecco’s modified Eagle’s medium

DMF:

Dimethyl formamide

DMSO:

Dimethyl sulfoxide

EDC:

1-Ethyl-3-(3-dimethyl-aminopropyl) carbodiimide

EDX:

Energy-dispersive X-ray spectroscopy

EMT:

Epithelial–mesenchymal transition

FBS:

Fetal bovine serum

FTIR:

Fourier-transform infrared spectroscopy

GO:

Graphene oxide

GQD:

Graphene quantum dot

af-GQD:

Amino-functionalized graphene quantum dots

GQD-HA:

Hyaluronic acid-amino-functionalized graphene quantum dots

HA:

Hyaluronic acid

rGO:

Reduced graphene oxide

NHS:

N-Hydroxysuccinimide

MES:

2-(N-Morpholino) ethanesulfonic acid hemi sodium salt

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PBS:

Phosphate-buffered saline

PEG:

Polyethylene glycol

SEM:

Scanning electron microscopy

TEM:

Transmission electron microscopy

UV:

Ultraviolet

Vis:

Visible

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Acknowledgements

This study was made possible by a grant with the number of 750 from the National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

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Correspondence to Matin Mahmoudifard.

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Avatefi, M., Mahmoudifard, M. & Moghadam, N.B. Amine-functionalized graphene quantum dots–hyaluronic acid nanocomposite as a high-resolution cancer cell bioimaging and biosensing system. Appl. Phys. A 129, 435 (2023). https://doi.org/10.1007/s00339-023-06700-3

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