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Graphene in biomedicine: opportunities and challenges

    Liangzhu Feng

    Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials, Soochow University, Suzhou, Jiangsu, 215123, China

    &
    Published Online:https://doi.org/10.2217/nnm.10.158

    Graphene, whose discovery won the 2010 Nobel Prize in physics, has been a shining star in the material science in the past few years. Owing to its interesting electrical, optical, mechanical and chemical properties, graphene has found potential applications in a wide range of areas, including biomedicine. In this article, we will summarize the latest progress of using graphene for various biomedical applications, including drug delivery, cancer therapies and biosensing, and discuss the opportunities and challenges in this emerging field.

    Bibliography

    • Novoselov KS, Geim AK, Morozov SV et al.: Electric field effect in atomically thin carbon films. Science306,666–669 (2004).
    • Liu Z, Robinson JT, Sun XM, Dai HJ: PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J. Am. Chem. Soc.130,10876–10877 (2008).
    • Sun XM, Liu Z, Welsher K et al.: Nano-graphene oxide for cellular imaging and drug delivery. Nano Res.1,203–212 (2008).
    • Mohanty N, Berry V: Graphene-based single-bacterium resolution biodevice and DNA transistor: interfacing graphene derivatives with nanoscale and microscale biocomponents. Nano Lett.8,4469–4476 (2008).
    • Zhang L M, Xia JG, Zhao QH, Liu LW, Zhang ZJ: Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs. Small6,537–544 (2010).
    • Yang XY, Zhang XY, Liu ZF, Ma YF, Huang Y, Chen Y: High-efficiency loading and controlled release of doxorubicin hydrochloride on graphene oxide. J. Phys. Chem. C.112,17554–17558 (2008).
    • Yang XY, Wang YS, Huang X et al.: Multi-functionalized graphene oxide based anticancer drug-carrier with dual-targeting function and pH-sensitivity. J. Mater. Chem. DOI: 10.1039/C0JM02494E (2011) (Epub ahead of print).
    • Yang K, Zhang S, Zhang G.X, Sun XM, Lee ST, Liu Z: Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett.10,3318–3323 (2010).
    • Zhou M, Zhai YM, Dong SJ: Electrochemical sensing and biosensing platform based on chemically reduced graphene oxide. Anal. Chem.81,5603–5613 (2009).
    • 10  Shan CS, Yang HF, Song JF, Han DX, Ivaska A, Niu L: Direct electrochemistry of glucose oxidase and biosensing for glucose based on graphene. Anal. Chem.81,2378–2382 (2009).
    • 11  Song YJ, Qu KG, Zhao C, Ren JS, Qu XG: Graphene oxide: intrinsic peroxidase catalytic activity and its application to glucose detection. Adv. Mater.22,2206–2210 (2010).
    • 12  Tang LAL, Wang JZ, Loh KP: Graphene-based SELDI probe with ultrahigh extraction and sensitivity for DNA oligomer. J. Am. Chem. Soc.132,10976–10977 (2010).
    • 13  Wang Y, Li ZH, Hu DH, Lin CT, Li JH, Lin YH: Aptamer/graphene oxide nanocomplex for in situ molecular probing in living cells. J. Am. Chem. Soc.132,9274–9276 (2010).
    • 14  Nelson T, Zhang B, Prezhdo OV: Detection of nucleic acids with graphene nanopores: ab initio characterization of a novel sequencing device. Nano Lett.10,3237–3242 (2010).
    • 15  Jung JH, Cheon DS, Liu F, Lee KB, Seo TS: A graphene oxide based immuno-biosensor for pathogen detection. Angew. Chem. Int. Ed.49,5708–5711 (2010).
    • 16  Hu WB, Peng C, Luo WJ et al.: Graphene-based antibacterial paper. ACS Nano.4,4317–4323 (2010).
    • 17  He SJ, Song B, Li D et al.: Graphene nanoprobe for rapid, sensitive, and multicolor fluorescent DNA analysis. Adv. Funct. Mater.20,453–459 (2010).
    • 18  Guo YS, Jia XP, Zhang SS: DNA cycle amplification device on magnetic microbeads for determination of thrombin based on graphene oxide enhancing signal-on electrochemiluminescence. Chem. Commun. DOI: 10.1039/C0CC03266B (2011) (Epub ahead of print).
    • 19  Gulbakan B, Yasun E, Ibrahim SM et al.: A dual platform for selective analyte enrichment and ionization in mass spectrometry using aptamer-conjugated graphene oxide. J. Am. Chem. Soc.132,17408–17410 (2010).
    • 20  Chang HX, Tang LH, Wang Y, Jiang JH, Li JH: Graphene fluorescence resonance energy transfer aptasensor for the thrombin detection. Anal. Chem.82,2341–2346 (2010).
    • 21  Loh KP, Bao QL, Ang PK, Yang JX: The chemistry of graphene. J. Mater. Chem.20,2277–2289 (2010).
    • 22  Geim AK: Graphene: status and prospects. Science324,1530–1534 (2009).
    • 23  Li XL, Wang XR, Zhang L, Lee SW, Dai HJ: Chemically derived, ultrasmooth graphene nanoribbon semiconductors. Science319,1229–1232 (2008).
    • 24  Loh KP, Bao Q, Eda G, Chhowalla M: Graphene oxide as a chemically tunable platform for optical applications. Nat. Chem.2,1015–24 (2010).
    • 25  Pan DY, Zhang JC, Li Z, Wu MH: Hydrothermal route for cutting graphene sheets into blue-luminescent graphene quantum dots. Adv. Mater.22,734–738 (2010).
    • 26  Dong HF, Gao WC, Yan F, Ji HX, Ju HX: Forescence resonance energy transfer between quantum dots and graphene oxide for sensing biomolecules. Anal.Chem.82,5511–5517 (2010).
    • 27  Jang HJ, Kim YK, Kwon HM, Yeo WS, Kim DE, Min DH: A graphene-based platform for the assay of duplex-DNA unwinding by helicase. Angew. Chem. Int. Ed.49,5703–5707 (2010).
    • 28  Lu CH, Li J, Liu JJ, Yang HH, Chen X, Chen GN: Increasing the sensitivity and single-base mismatch selectivity of the molecular beacon using graphene oxide as the “nanoquencher”. Chem. Eur. J.16,4889–4894 (2010).
    • 29  Lu CH, Li JA, Lin MH et al.: Amplified aptamer-based assay through catalytic recycling of the analyte. Angew. Chem. Int. Ed.49,8454–8457 (2010).
    • 30  Peng C, Hu W, Zhou Y, Fan CH, Huang Q: Intracellular imaging with a graphene-based fluorescent probe. Small6,1686–92 (2010).
    • 31  Liu F, Choi JY, Seo TS: Graphene oxide arrays for detecting specific DNA hybridization by fluorescence resonance energy transfer. Biosens. Bioelectro.25,2361–2365 (2010).
    • 32  Geim AK, Novoselov KS: The rise of graphene. Nat. Mater.6,183–191(2007).
    • 33  Hummers WS, Offeman RE: Preparation of graphitic oxide. J. Am. Chem. Soc.80,1339 (1958).
    • 34  Quintana M, Spyrou K, Grzelczak M, Browne WR, Rudolf P, Prato M: Functionalization of graphene via 1,3-dipolar cycloaddition. ACS Nano.4,3527–3533 (2010).
    • 35  He SJ, Song B, Li D et al.: Graphene nanoprobe for rapid, sensitive, and multicolor fluorescent DNA analysis. Adv. Funct. Mater.20,453–459 (2010).
    • 36  Lu CH, Zhu CL, Li J, Liu JJ, Chen X, Yang HH: Using graphene to protect DNA from cleavage during cellular delivery. Chem. Commun.46,3116–3168 (2010).
    • 37  Balapanuru J, Yang JX, Xiao S et al.: Graphene oxide–organic dye ionic complex with DNA-Sensing and optical-limiting properties. Angew. Chem. Int. Ed.49,6549–6553 (2010).
    • 38  Chen D, Tang L, Li J: Graphene-based materials in electrochemistry. Chem. Soc. Rev.39,3157–3180 (2010).
    • 39  Ohno Y, Maehashi K, Yamashiro Y, Matsumoto K: Electrolyte-gated graphene field-effect transistors for detecting pH protein adsorption. Nano Lett.9,3318–3322 (2009).
    • 40  Zeng QO, Cheng JS, Tang LH et al.: Self-assembled graphene–enzyme hierarchical nanostructures for electrochemical biosensing. Adv. Funct. Mater.20,3366–3372 (2010).
    • 41  Chen XP, Ye HZ, Wang WZ, Qui B, Lin ZY, Chen GN: Electrochemiluminescence biosensor for glucose based on graphene/nafion/GOD film modified glassy carbon electrode. Electroanalysis22,2347–2352 (2010).
    • 42  Shao YY, Wang J, Wu H, Liu J, Aksay IA, Lin YH: Graphene based electrochemical sensors and biosensors: a review. Electroanalysis22,1027–1036 (2010).
    • 43  Cohen-Karni T, Qing Q, Li Q, Fang Y, Lieber CM: Graphene and nanowire transistors for cellular interfaces and electrical recording. Nano Lett.10,1098–1102 (2010).
    • 44  Dong XC, Shi YM, Huang W, Chen P, Li LJ: Electrical detection of DNA hybridization with single-base specificity using transistors based on CVD-grown graphene sheets. Adv. Mater.22,1649–1653 (2010).
    • 45  Stine R, Robinson JT, Sheehan PE, Tamanaha CR: Real-time DNA detection using reduced graphene oxide field effect transistors. Adv. Mater.22(46),5297–5300 (2010).
    • 46  Zhou M, Zhai YM, Dong SJ: Electrochemical sensing and biosensing platform based on chemically reduced graphene oxide. Anal. Chem.81,5603–5613 (2009).
    • 47  Liu Y, Yu DS, Zeng C, Miao ZC, Dai LM: Biocompatible graphene oxide-based glucose biosensors. Langmuir26,6158–6160 (2010).
    • 48  Kang XH, Wang J, Wu H, Aksay IA, Liu J, Lin YH: Glucose oxidase–grapheme–chitosan modified electrode for direct electrochemistry and glucose sensing. Biosens. Bioelectro.25,901–905 (2009).
    • 49  Lim CX, Hoh HY, Ang PK, Loh KP: Direct voltammetric detection of DNA and pH sensing on epitaxial graphene: an insight into the role of oxygenated defects. Anal. Chem.82,7387–7393 (2010).
    • 50  Lu CH, Yang HH, Zhu CL, Chen X, Chen GN: A graphene platform for sensing biomolecules. Angew. Chem. Int. Ed.48,4785–4787 (2009).
    • 51  Dong XL, Cheng JS, Li JH, Wang YS. Graphene as a novel matrix for the analysis of small molecules by MALDI-TOF MS. Anal. Chem.82,6208–6214 (2010).
    • 52  Baby TT, Aravind SSJ, Arockiadoss T, Rakhi RB, Ramaprabhu S: Metal decorated graphene nanosheets as immobilization matrix for amperometric glucose biosensor. Sensor Actuat. B Chem.145,71–77 (2010).
    • 53  Mao S, Lu GH, Yu KH, Bo Z, Chen JH: specific protein detection using thermally reduced graphene oxide sheet decorated with gold nanoparticle–antibody conjugates. Adv. Mater.22,3521–3526 (2010).
    • 54  Wang K, Liu QA, Wu XY, Guan QM, Li HN: Graphene enhanced electrochemiluminescence of CdS nanocrystal for H2O2 sensing. Talanta82,372–376 (2010).
    • 55  Xia TA, Kovochich, M, Liong M et al.: Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs. ACS Nano.3,3273–3286 (2009).
    • 56  Liu Z, Tabakman S, Welsher K, Dai HJ: Carbon nanotubes in biology and medicine: in vitro and in vivo detection, imaging and drug delivery. Nano Res.2,85–120 (2009).
    • 57  Markovic ZM, Harhaji-Trajkovic LM, Todorovic-Markovic BM et al.: In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes. Biomaterials32,1121–1129 (2010).
    • 58  Zhang YB, Ali SF, Dervishi E et al.: Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. ACS Nano.4,3181–3186 (2010).
    • 59  Wang K, Ruan J, Song H et al.: Biocompatibility of graphene oxide. Nanoscale. Res. Lett. DOI 10.1007/s11671–010–9751–6 (2010) (Epub ahead of print).
    • 60  Ryoo SR, Kim YK, Kim MH, Min DH: Behaviors of NIH-3T3 fibroblasts on graphene/carbon nanotubes: proliferation, focal adhesion, and gene transfection studies. ACS Nano.4,6587–6598 (2010).
    • 61  Zhang XY, Yin JL, Peng C et al.: Distribution and biocompatibility studies of graphene oxide in mice after intravenous administration. Carbon. DOI: 10.1016/j.carbon.2010.11.005 (2010) (Epub ahead of print).
    • 62  Yang K, Wan JM, Zhang S, Zhang YJ, Lee ST, Liu Z: In vivo pharmacokinetics, long-term biodistribution and toxicology of PEGylated graphene in mice. ACS Nano.5,516–522 (2011).
    • 63  Liu Z, Yang K, Lee ST: Single-walled carbon nanotubes in biomedical imaging. J. Mater. Chem. DOI: 10.1039/C0JM02020F (2011) (Epub ahead of print).
    • 64  Liu Z, Tabakman SM, Chen Z, Dai HJ: Preparation of carbon nanotube bioconjugates for biomedical applications. Nat. Protoc.4,1372–1382 (2009).
    • 65  Zhang S, Yang K, Liu Z: Carbon nanotubes for in vivo cancer nanotechnology. Sci. China. Ser. B.53,2217–2225 (2010).
    • 66  Liu X, Tao H, Yang K, Zhang S, Lee ST, Liu Z: Optimization of surface chemistry on single-walled carbon nanotubes for in vivo photothermal ablation of tumors. Biomaterials32,144–151 (2011).
    • 67  Liu Z, Cai WB, He LN et al.: In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nat. Nanotech.2,47–52 (2007).
    • 68  Li F, Huang Y, Yang Q et al.: A graphene-enhanced molecular beacon for homogeneous DNA detection. Nanoscale2,1021–1026 (2010).
    • 69  Wen Y, Xing F, He S et al.: A graphene-based fluorescent nanoprobe for silver(I) ions detection by using graphene oxide and a silver-specific oligonucleotide. Chem. Commun (Camb.)46,2596–2598 (2010).
    • 70  Du D, Zou ZX, Shin YS et al.: Sensitive immunosensor for cancer biomarker based on dual signal amplification strategy of graphene sheets and multienzyme functionalized carbon nanospheres. Anal. Chem.82,2989–2995 (2010)
    • 71  Xu CH, Wang XB, Wang JC, Hu HT, Wan L: Synthesis and photoelectrical properties of β-cyclodextrin functionalized graphene materials with high bio-recognition capability. Chem. Phys. Lett.498,162–167 (2010).
    • 72  Du M, Yang T, Jiao K: Immobilization-free direct electrochemical detection for DNA specific sequences based on electrochemically converted gold nanoparticles/graphene composite film. J. Mater. Chem.20,9253–9260 (2010).
    • 73  Wang Y, Shao YY, Matson DW, Li JH, Lin YH: Nitrogen-doped graphene and its application in electrochemical biosensing. ACS Nano.4,1790–1798 (2010).
    • 74  Lv W, Guo M, Liang MH et al.: Graphene–DNA hybrids: self-assembly and electrochemical detection performance. J. Mater. Chem.20,6668–6673 (2010).
    • 75  Yin HS, Zhou YL, Ma QA et al.: Electrochemical oxidation behavior of guanine and adenine on graphene-nafion composite film modified glassy carbon electrode and the simultaneous determination. Process Biochem.45,1707–1712 (2010).
    • 76  Ang PK, Chen W, Wee ATS, Loh KP: Solution-gated epitaxial graphene as pH sensor. J. Am. Chem. Soc.130,14392–14393 (2008).
    • 77  Park S, Mohanty N, Suk JW et al.: Biocompatible, robust free-standing paper composed of a TWEEN/graphene composite. Adv. Mater.22,1736–1740 (2010).
    • 78  Kalbacova M, Broz A, Kong J, Kalbac M: Graphene substrates promote adherence of human osteoblasts and mesenchymal stromal cells. Carbon48,4323–4329 (2010).
    • 79  Chen H, Muller MB, Gilmore KJ, Wallace GG, Li D: Mechanically strong, electrically conductive, and biocompatible graphene paper. Adv. Mater.20,3557–3561 (2008).
    • 80  Fan HL, Wang LL, Zhao KK et al.: Fabrication, mechanical properties, and biocompatibility of graphene-reinforced chitosan composites. Biomacromolecules.11,2345–2351 (2010).
    • 81  Kroto HW, Heath JR, O’Brien SC, Curl RF, Smalley RE: C60: buckminsterfullerene. Nature318,162–163 (1985).
    • 82  Iijima S: Helical microtubules of graphitic carbon. Nature354,56–58 (1991).