Graphene in Biomedicine: Opportunities and Challenges

Graphene versus Carbon Nanotubes in Biomedicine

As the 'bigger sister' of graphene, carbon nanotubes have been extensively explored in biomedicine since 2004, showing promising applications in biosensors, drug and gene delivery, novel cancer therapies, as well as biomedical imaging.^[56,63–65] Therefore, a natural question arises regarding how graphene compares with carbon nanotubes in biomedical applications. Although GO can be massively produced at a price that is almost negligible, the polymers (e.g., PEG) used to modify graphene are still expensive and, thus, the total cost to synthesize a functional graphene bioconjugate is not significantly lower than that for carbon nanotubes. Regarding properties, single-walled carbon nanotubes (SWNTs) exhibit strong resonance Raman scattering and NIR band-gap photoluminescence (for semiconducting nanotubes), which have been proven to be useful in biomedical imaging applications.^[56,63] Unfortunately, graphene does not have these optical properties and its application in imaging may need external labels. At the same weight concentration, the optical density of GO in the NIR region, which is useful for photothermal therapy and potentially for photoacoustic imaging, is a few times lower than that of SWNTs,^[8,66] unless GO is reduced. Interestingly, a latest work by Markovic et al. reported that although nano-graphene displays lower NIR-absorbing capability, its photothermal responsiveness and in vitro photothermal cancer cell killing efficiency is better than that of carbon nanotubes.^[57] However, the exact mechanism behind this encouraging discovery, although proposed by the authors to be better dispersivity of graphene, may require further experimental validations.

Then why are we still interested in graphene-based biomedicine? First, single-layered graphene sheets have two sides exposed on the surface and, thus, at least a doubled external surface area than SWNTs. In our animal experiment we found an extremely high tumor passive targeting effect for NGO-PEG, likely via the tumor-enhanced permeability and retention effect, attractive for cancer therapy applications.^[8] The passive tumor targeting effect of the 2D nano-graphene appears to be more efficient than that of the 1D SWNTs,^[67] and is likely attributed to the unique shape and size of nanographene that favor the enhanced permeability and retention effect. For biosensing devices, the graphene devices could potentially have a better reproducibility compared with SWNT devices since each single nanotube has a different chirality and, thus, entirely different electric properties. Moreover, the 2D graphene sheets may be easily complexed to various other functional nanoparticles for potential multimodality imaging and therapy applications, while the nanoparticle modification on individual nanotubes is relatively more complicated.

Cite this: Graphene in Biomedicine: Opportunities and Challenges - Medscape - Mar 01, 2011.

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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