Science Bulletin

, Volume 60, Issue 7, pp 665–678 | Cite as

Organic–inorganic nanohybrids for fluorescence, photoacoustic and Raman bioimaging

  • Sivaramapanicker Sreejith
  • Tran Thi Mai Huong
  • Parijat Borah
  • Yanli ZhaoEmail author
Review Chemistry


Organic–inorganic nanohybrid materials represent a wide range of nanoscaled synthetic materials consisting of both organic and inorganic components that are linked together by covalent or non-covalent interactions, which have been widely employed in various fields such as optoelectronics, catalysis and biomedicine. As a result of this special combination, nanohybrid materials assemble numerous extraordinary features that provide great opportunities to improve their stability, multifunctions, biocompatibility, eco-friendliness and other physical and mechanical properties. This review highlights recent research developments of functional organic–inorganic nanohybrid materials and their specific applications in bioimaging including fluorescent, Raman, photoacoustic and combined bioimaging. Future research directions and perspectives in this rapidly developing field are also discussed.


Bioimaging Combined imaging Functional nanomaterials Organic–inorganic hybrid Photoacoustic imaging 





生物成像 组合成像 功能纳米材料 有机-无机杂化材料 光声成像 



This work was supported by the National Research Foundation (NRF), Prime Minister’s Office, Singapore, under its NRF Fellowship (NRF2009NRF-RF001-015) and Campus for Research Excellence and Technological Enterprise (CREATE) Programme—Singapore Peking University Research Centre for a Sustainable Low-Carbon Future, the NTU-A*STAR Silicon Technologies Centre of Excellence under the program Grant No. 11235150003 and the NTU-Northwestern Institute for Nanomedicine.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Costi R, Saunders AE, Banin U (2010) Colloidal hybrid nanostructures: a new type of functional materials. Angew Chem Int Ed 49:4878–4897CrossRefGoogle Scholar
  2. 2.
    Biju V (2014) Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy. Chem Soc Rev 43:744–764CrossRefGoogle Scholar
  3. 3.
    Mu Q, Jiang G, Chen L et al (2014) Chemical basis of interactions between engineered nanoparticles and biological systems. Chem Rev 114:7740–7781CrossRefGoogle Scholar
  4. 4.
    Nguyen KT, Zhao Y (2014) Integrated graphene/nanoparticle hybrids for biological and electronic applications. Nannoscale 6:6245–6266CrossRefGoogle Scholar
  5. 5.
    Liang R, Wei M, Evans DG et al (2014) Inorganic nanomaterials for bioimaging, targeted drug delivery and therapeutics. Chem Commun 50:14071–14081CrossRefGoogle Scholar
  6. 6.
    Naoi K, Naoi W, Aoyagi S et al (2013) New generation nanohybrid supercapacitor. Acc Chem Res 46:1075–1083CrossRefGoogle Scholar
  7. 7.
    Suetens P (2009) Fundamentals of medical imaging, 2nd edn. Cambridge University Press, New YorkCrossRefGoogle Scholar
  8. 8.
    Lee DE, Koo H, Sun IC et al (2012) Multifunctional nanoparticles for multimodal imaging and theragnosis. Chem Soc Rev 41:2656–2672CrossRefGoogle Scholar
  9. 9.
    Jakhmola A, Anton N, Vandamme TF (2012) Inorganic nanoparticles based contrast agents for X-ray computed tomography. Adv Healthc Mater 1:413–431CrossRefGoogle Scholar
  10. 10.
    Taylor A, Wilson KM, Murray P et al (2012) Long-term tracking of cells using inorganic nanoparticles as contrast agents: are we there yet? Chem Soc Rev 41:2707–2717CrossRefGoogle Scholar
  11. 11.
    Weissleder R, Pittet MJ (2008) Imaging era of molecular oncology. Nature 452:580–589CrossRefGoogle Scholar
  12. 12.
    Lichtman JW, Conchello J (2005) Fluorescence microscopy. Nat Methods 2:910–919CrossRefGoogle Scholar
  13. 13.
    Shen L (2011) Biocompatible polymer/quantum dots hybrid materials: current status and future developments. J Funct Biomater 2:355–372CrossRefGoogle Scholar
  14. 14.
    Brunner TJ, Wick P, Manser P et al (2006) In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility. Environ Sci Technol 40:4374–4381CrossRefGoogle Scholar
  15. 15.
    Ow H, Larson DR, Srivastava M et al (2005) Bright and stable core-shell fluorescent silica nanoparticles. Nano Lett 5:113–117CrossRefGoogle Scholar
  16. 16.
    Zhao X, Tapec-Dytioco R, Tan W (2003) Ultrasensitive DNA detection using highly fluorescent bioconjugated nanoparticles. J Am Chem Soc 125:11474–11475CrossRefGoogle Scholar
  17. 17.
    Jain TK, Roy I, De TK et al (1998) Nanometer silica particles encapsulating active compounds: a novel ceramic drug carrier. J Am Chem Soc 120:11092–11095CrossRefGoogle Scholar
  18. 18.
    Cordek J, Wang X, Tan W (1999) Direct immobilization of glutamate dehydrogenase on optical fiber probes for ultrasensitive glutamate detection. Anal Chem 71:1529–1533CrossRefGoogle Scholar
  19. 19.
    Fang XH, Liu X, Schuster S et al (1999) Designing a novel molecular beacon for surface-immobilized DNA hybridization studies. J Am Chem Soc 121:2921–2922CrossRefGoogle Scholar
  20. 20.
    Kumar R, Roy I, Ohulchanskyy TY et al (2008) Covalently dye-linked, surface controlled, and bioconjugated organically modified silica nanoparticles as targeted probes for optical imaging. ACS Nano 2:449–458CrossRefGoogle Scholar
  21. 21.
    Zhong Y, Peng F, Wei X et al (2012) Microwave-assisted synthesis of biofunctional and fluorescent silicon nanoparticles using proteins as hydrophobic ligands. Angew Chem Int Ed 51:8485–9489CrossRefGoogle Scholar
  22. 22.
    Schick I, Lorentz S, Gehrig D et al (2014) Multifunctional two-photon active silica coated Au@MnO Janus particles for selective dual functionalization and imaging. J Am Chem Soc 136:2473–2483CrossRefGoogle Scholar
  23. 23.
    Sharma P, Bengtsson NE, Walter GA et al (2012) Gadolinium-doped silica nanoparticles encapsulating indocyanine green for near infrared and magnetic resonance imaging. Small 8:2856–2868CrossRefGoogle Scholar
  24. 24.
    Popat A, Hartono SB, Stahr F et al (2011) Mesoporous silica nanoparticles for bioadsorption, enzyme immobilization, and drug delivery carriers. Nanoscale 3:2801–2818CrossRefGoogle Scholar
  25. 25.
    Manzano M, Vallet-Regi M (2010) New developments in ordered mesoporous materials for drug delivery. J Mater Chem 20:5593–5604CrossRefGoogle Scholar
  26. 26.
    Ambrogio MW, Thomas CR, Zhao YL et al (2011) Mechanized silica nanoparticles: a new frontier in theranostic nanomedicine. Acc Chem Res 44:903–913CrossRefGoogle Scholar
  27. 27.
    Wu S, Zhu C (1999) All-solid-state UV dye laser pumped by XeCl laser. Opt Mater 12:99–103CrossRefGoogle Scholar
  28. 28.
    Fiorilli S, Onida B, Macquarrie D et al (2004) Mesoporous SBA-15 silica impregnated with Reichardt’s dye: a material optically responding to NH3. Sens Actuators B Chem 100:103–106CrossRefGoogle Scholar
  29. 29.
    Lin YS, Tsai CP, Huang HY et al (2005) Well-ordered mesoporous silica nanoparticles as cell markers. Chem Mater 17:4570–4573CrossRefGoogle Scholar
  30. 30.
    Gianotti E, Bertolino CA, Benzi C et al (2009) Photoactive hybrid nanomaterials: indocyanine immobilized in mesoporous MCM-41 for “in cell” bioimaging. ACS Appl Mater Interfaces 1:678–687CrossRefGoogle Scholar
  31. 31.
    Ma X, Sreejith S, Zhao Y (2013) Spacer intercalated disassembly and photodynamic activity of zinc phthalocyanine inside nanochannels of mesoporous silica nanoparticles. ACS Appl Mater Interfaces 5:12860–12868CrossRefGoogle Scholar
  32. 32.
    Prabhakar N, Näreoja T, von Haartman E et al (2013) Core-shell designs of photoluminescent nanodiamonds with porous silica coatings for bioimaging and drug delivery II: application. Nanoscale 5:3713–3722CrossRefGoogle Scholar
  33. 33.
    Sreejith S, Ma X, Zhao Y (2012) Graphene oxide wrapping on squaraine-loaded mesoporous silica nanoparticles for bioimaging. J Am Chem Soc 134:17346–17349CrossRefGoogle Scholar
  34. 34.
    Sreejith S, Carol P, Chithra P et al (2008) Squaraine dyes: a mine of molecular materials. J Mater Chem 18:264–274CrossRefGoogle Scholar
  35. 35.
    Sreejith S, Divya KP, Ajayaghosh A (2008) A near-infrared dye as a latent ratiometric fluorophore for the detection of aminothiol content in blood plasma. Angew Chem Int Ed 47:7883–7887CrossRefGoogle Scholar
  36. 36.
    Dresselhaus MS, Jorio A, Hofmann M et al (2010) Perspectives on carbon nanotubes and graphene Raman spectroscopy. Nano Lett 10:751–758CrossRefGoogle Scholar
  37. 37.
    Roy D, Chhowalla M, Sano N et al (2003) Characterisation of carbon nano-onions using Raman spectroscopy. Chem Phys Lett 373:52–56CrossRefGoogle Scholar
  38. 38.
    Eklund PC, Holden JM, Jishi RA (1995) Vibrational modes of carbon nanotubes: spectroscopy and theory. Carbon 33:959–972CrossRefGoogle Scholar
  39. 39.
    Heller DA, Baik S, Eurell TE et al (2005) Single-walled carbon nanotube spectroscopy in live cells: towards long-term labels and optical sensors. Adv Mater 17:2793–2799CrossRefGoogle Scholar
  40. 40.
    Liu Z, Winters M, Holodniy M et al (2007) siRNA delivery into human T cells and primary cells with carbon-nanotube transporters. Angew Chem Int Ed 46:2023–2027CrossRefGoogle Scholar
  41. 41.
    Liu Z, Li X, Tabakman SC et al (2008) Multiplexed multicolor Raman imaging of live cells with isotopically modified single walled carbon nanotubes. J Am Chem Soc 130:13540–13541CrossRefGoogle Scholar
  42. 42.
    Fan W, Lee YH, Peddireddy S et al (2014) Graphene oxide and shape-controlled silver nanoparticle hybrids for ultrasensitive single particle surface-enhanced Raman scattering (SERS) sensing. Nanoscale 6:4843–4851CrossRefGoogle Scholar
  43. 43.
    Ma X, Qu Q, Zhao Y et al (2013) Graphene oxide wrapped gold nanoparticles for intracellular Raman imaging and drug delivery. J Mater Chem B 1:6495–6500CrossRefGoogle Scholar
  44. 44.
    Qian X, Zhou X, Nie S (2008) Surface-enhanced Raman nanoparticle beacons based on bioconjugated gold nanocrystals and long range plasmonic coupling. J Am Chem Soc 130:14934–14935CrossRefGoogle Scholar
  45. 45.
    Narayanan TN, Gupta BK, Vithayathil SA et al (2012) Hybrid 2D nanomaterials as dual-mode contrast agents in cellular imaging. Adv Mater 24:2992–2998CrossRefGoogle Scholar
  46. 46.
    Zhang H, Ma X, Nguyen KT et al (2014) Water-soluble pillararene-functionalized graphene oxide for in vitro Raman and fluorescence dual-mode imaging. ChemPlusChem 79:462–469CrossRefGoogle Scholar
  47. 47.
    Yang X, Stein EW, Ashkenazi S et al (2009) Nanoparticles for photoacoustic imaging. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1:360–368CrossRefGoogle Scholar
  48. 48.
    Zhou T, Wu B, Xing D (2012) Bio-modified Fe3O4 core/Au shell nanoparticles for targeting and multimodal imaging of cancer cells. J Mater Chem 22:470–477CrossRefGoogle Scholar
  49. 49.
    Mallidi S, Larson T, Tam J et al (2009) Multiwavelength photoacoustic imaging and plasmon resonance coupling of gold nanoparticles for selective detection of cancer. Nano Lett 9:2825–2831CrossRefGoogle Scholar
  50. 50.
    Zhang Q, Iwakuma N, Sharma P et al (2009) Gold nanoparticles as a contrast agent for in vivo tumor imaging with photoacoustic tomography. Nanotechnology 20:395102CrossRefGoogle Scholar
  51. 51.
    Sharma P, Brown SC, Bengtsson N et al (2008) Gold-speckled multimodal nanoparticles for noninvasive bioimaging. Chem Mater 20:6087–6094CrossRefGoogle Scholar
  52. 52.
    Bouchard LS, Anwar MS, Liu GL et al (2009) Picomolar sensitivity MRI and photoacoustic imaging of cobalt nanoparticles. Proc Natl Acad Sci USA 106:4085–4089CrossRefGoogle Scholar
  53. 53.
    Sreejith S, Joseph J, Nguyen KT et al (2015) Graphene oxide wrapping of gold-silica core-shell nanohybrids for photoacoustic signal generation and bimodal imaging. ChemNanoMat. doi: 10.1002/cnma.201400017 Google Scholar
  54. 54.
    Li PC, Wang CRC, Shieh DB et al (2008) In vivo photoacoustic molecular imaging with simultaneous multiple selective targeting using antibody-conjugated gold nanorods. Opt Express 16:18605–18615CrossRefGoogle Scholar
  55. 55.
    Pan D, Pramanik M, Senpan A et al (2010) A facile synthesis of novel self-assembled gold nanorods designed for near-infrared imaging. J Nanosci Nanotechnol 10:8118–8123CrossRefGoogle Scholar
  56. 56.
    Kim C, Song HM, Cai X et al (2011) In vivo photoacoustic mapping of lymphatic systems with plasmon-resonant nanostars. J Mater Chem 21:2841–2844CrossRefGoogle Scholar
  57. 57.
    Cai X, Li W, Kim CH et al (2011) In vivo quantitative evaluation of the transport kinetics of gold nanocages in a lymphatic system by noninvasive photoacoustic tomography. ACS Nano 5:9658–9667CrossRefGoogle Scholar
  58. 58.
    Song KH, Kim C, Cobley CM et al (2009) Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model. Nano Lett 9:183–188CrossRefGoogle Scholar
  59. 59.
    Kim C, Cho EC, Chen J et al (2010) In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages. ACS Nano 4:4559–4564CrossRefGoogle Scholar
  60. 60.
    Lu W, Huang Q, Ku G et al (2010) Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres. Biomaterials 31:2617–2626CrossRefGoogle Scholar
  61. 61.
    Chen YS, Frey W, Kim S et al (2011) Silica-coated gold nanorods as photoacoustic signal nanoamplifiers. Nano Lett 11:348–354CrossRefGoogle Scholar
  62. 62.
    Chen YS, Frey W, Kim S et al (2010) Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy. Opt Express 18:8867–8877CrossRefGoogle Scholar
  63. 63.
    Chen LC, Wei CW, Souris JS et al (2010) Enhanced photoacoustic stability of gold nanorods by silica matrix confinement. J Biomed Opt 15:016010CrossRefGoogle Scholar
  64. 64.
    Jokerst JV, Thangaraj M, Kempen PJ et al (2012) Photoacoustic imaging of mesenchymal stem cells in living mice via silica-coated gold nanorods. ACS Nano 6:5920–5930CrossRefGoogle Scholar
  65. 65.
    Kalele S, Gosavi SW, Urban J et al (2006) Nanoshell particles: synthesis, properties and applications. Curr Sci 91:1038–1052Google Scholar
  66. 66.
    Huang X, Neretina S, El-Sayed MA (2009) Gold nanorods: from synthesis and properties to biological and biomedical applications. Adv Mater 21:4880–4910CrossRefGoogle Scholar
  67. 67.
    Alkilany AM, Murphy CJ (2010) Toxicity and cellular uptake of gold nanoparticles: what we have learned so far? J Nanopart Res 12:2313–2333CrossRefGoogle Scholar
  68. 68.
    de La Zerda A, Zavaleta C, Keren S et al (2008) Carbon nanotubes as photoacoustic molecular imaging agents in living mice. Nat Nanotechnol 3:557–562CrossRefGoogle Scholar
  69. 69.
    Kim JW, Galanzha EI, Shashkov EV et al (2009) Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents. Nat Nanotechnol 4:688–694CrossRefGoogle Scholar
  70. 70.
    de la Zerda A, Liu Z, Bodapati S et al (2010) Ultrahigh sensitivity carbon nanotube agents for photoacoustic molecular imaging in living mice. Nano Lett 10:2168–2172CrossRefGoogle Scholar
  71. 71.
    Maji SK, Sreejith S, Joseph J et al (2014) Upconversion nanoparticles as a contrast agent for photoacoustic imaging in live mice. Adv Mater 26:5633–5638CrossRefGoogle Scholar
  72. 72.
    Dowling MB, Li L, Park J et al (2010) Multiphoton-absorption-induced-luminescence (MAIL) imaging of tumor-targeted gold nanoparticles. Bioconjugate Chem 21:1968–1977CrossRefGoogle Scholar
  73. 73.
    Voliani V, Ricci F, Signore G et al (2011) Multiphoton molecular photorelease in click-chemistry-functionalized gold nanoparticles. Small 7:3271–3275CrossRefGoogle Scholar
  74. 74.
    Cao L, Wang X, Meziani MJ et al (2007) Carbon dots for multiphoton bioimaging. J Am Chem Soc 129:11318–11319CrossRefGoogle Scholar
  75. 75.
    Li JL, Bao HC, How XL et al (2012) Graphene oxide nanoparticles as a nonleaching optical probe for two-photon luminescence imaging and cell therapy. Angew Chem Int Ed 51:1830–1834CrossRefGoogle Scholar
  76. 76.
    Qian J, Wang D, Cai FH et al (2012) Observation of multiphoton-induced fluorescence from graphene oxide nanoparticles and applications in in vivo functional bioimaging. Angew Chem Int Ed 51:10570–10575CrossRefGoogle Scholar
  77. 77.
    Nguyen KT, Sreejith S, Joseph J et al (2014) Poly(acrylic acid) capped and dye loaded graphene oxide-mesoporous silica: a nano-sandwich for two-photon and photoacoustic dual mode imaging. Part Part Syst Charact 31:1060–1061CrossRefGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Sivaramapanicker Sreejith
    • 1
  • Tran Thi Mai Huong
    • 1
  • Parijat Borah
    • 1
  • Yanli Zhao
    • 1
    • 2
    Email author
  1. 1.Division of Chemistry and Biological Chemistry, School of Physical and Mathematical SciencesNanyang Technological UniversitySingaporeSingapore
  2. 2.School of Materials Science and EngineeringNanyang Technological UniversitySingaporeSingapore

Personalised recommendations