Graphene in Biomedicine: Opportunities and Challenges

Liangzhu Feng; Zhuang Liu

Nanomedicine. 2011;6(2):317-324.

Graphene for Biosensing

In the past 2 years, there have been a significant number of publications reporting graphene-based biosensors,^{[4,9–14,27,35–42]} mainly utilizing the unique chemical, optical, electrical and electrochemical properties of graphene. It has been found that the nucleotide bases in ssDNA bind strongly to the graphene surface by ϖ-ϖ stacking, which could be greatly weakened after DNA hybridization to form dsDNA.^{[17,20,27–29,37]} Several different groups have utilized this phenomenon, as well as the effective fluorescence-quenching ability of graphene, to develop novel graphene-based DNA detection platforms.^{[13,27,35–37]} Fan and co-workers reported a GO-based multicolor DNA probe for rapid, sensitive and selective detection of DNA targets in solutions.^[35] Others found that graphene could deliver oligonucleotides, such as molecular beacons and aptamers, into living cells for in situ probing of biomolecules.^[13,36]

Many other graphene-based biosensing systems using different mechanisms have also been studied by many groups.^{[4,38,41,43,44]} In 2008, Mohanty et al. for the first time successfully fabricated graphene electronic devices for detection of bacterium, DNA and proteins.^[4] Since then, biosensing using graphene electronic devices has been actively pursued.^{[14,39,43–45]} Owing to its ultra-high surface area and excellent electron mobility, graphene or graphene-based composite materials were used to modify electrodes in the eletrochemical sensing of various biomolecules, including glucose, DNA and proteins, with high sensitivities.^[40,46–50] Recently, a number of groups have also used graphene as a novel matrix for mass spectrometry assay of biological molecules.^[12,19,51] Furthermore, graphene could also be combined with other nanomaterials for various novel biosensing applications.^[15,52–55]

Despite the large amount of recent publications on graphene-based biosensors, the advantages of those novel biomolecular detection platforms over conventional bioassay tools remain to be clarified. Although high detection sensitivities have been achieved by many graphene-based biosensors, their reliability and reproducibility may need careful examinations. Similar to many other nano-biosensor systems, the batch-to-batch variations in those graphene biosensors need more attention and may be minimized by further work.

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Table 1. Biomedical applications of graphene.
Application	Example	Ref.
*Graphene-based biosensors*
Optical sensing	Oligonucleotides (e.g., ssDNA, molecular beacons and aptamers)	[13,17,26,27,29,36,68]
	Proteins (e.g., thrombin)	[20,50,68]
	Heavy metal ions (e.g., Ag)	[69]
	Pathogen (e.g., rotavirus)	[15]
Electrochemical sensing	Biomacromolecules (e.g., DNA, hemoglobin and α-fetoprotein)	[46,70–72]
	Enzymes (e.g., horseradish peroxidase and glucose oxidase)	[10,40,49,73]
	Small molecules (e.g., hydrogen peroxide, β-nicotinamide adenine dinucleotide, dopamine and glucose)	[11,50,74,75]
Electronic devices	Proteins, DNA, bacterium and pH values	[4,14,39,43,44,53,76]
Matrix for mass spectra	Small molecules (e.g., cocaine and adenosine) or DNA	[12,19,51]
*Graphene for potential cancer therapy*
Drug delivery	Loading of chemotherapy drugs (e.g., doxorubicin and SN38)	[2,3,5–7]
Drug delivery	In vitro cancer cell targeting (e.g., using antibodies, peptide and folate acid)	[3,5,7]
Photothermal therapy	In vitro cancer cell killing under near-infrared light, better than carbon nanotubes	[57]
Photothermal therapy	Ultra-high in vivo tumor uptake and efficient photothermal ablation of cancer in mice	[8]
*Other applications*
Fluorescence imaging probes		[3,30]
Antibacteria papers		[16,77]
Tissue engineering scaffolds		[77–80]

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