Skip to main content

Advertisement

SpringerLink
Log in

Oligonucleotide optical switches for intracellular sensing

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Fluorescence imaging coupled with nanotechnology is making possible the development of powerful tools in the biological field for applications such as cellular imaging and intracellular messenger RNA monitoring and detection. The delivery of fluorescent probes into cells and tissues is currently receiving growing interest because such molecules, often coupled to nanodimensional materials, can conveniently allow the preparation of small tools to spy on cellular mechanisms with high specificity and sensitivity. The purpose of this review is to provide an exhaustive overview of current research in oligonucleotide optical switches for intracellular sensing with a focus on the engineering methods adopted for these oligonucleotides and the more recent and fascinating techniques for their internalization into living cells. Oligonucleotide optical switches can be defined as specifically designed short nucleic acid molecules capable of turning on or modifying their light emission on molecular interaction with well-defined molecular targets. Molecular beacons, aptamer beacons, hybrid molecular probes, and simpler linear oligonucleotide switches are the most promising optical nanosensors proposed in recent years. The intracellular targets which have been considered for sensing are a plethora of messenger-RNA-expressing cellular proteins and enzymes, or, directly, proteins or small molecules in the case of sensing through aptamer-based switches. Engineering methods, including modification of the oligonucleotide itself with locked nucleic acids, peptide nucleic acids, or l-DNA nucleotides, have been proposed to enhance the stability of nucleases and to prevent false-negative and high background optical signals. Conventional delivery techniques are treated here together with more innovative methods based on the coupling of the switches with nano-objects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Pawley JB (2006) Handbook of biological confocal microscopy, 3rd edn. Springer, Berlin

    Book  Google Scholar 

  2. Huang K, Martí AA (2012) Recent trends in molecular beacon design and applications. Anal Bioanal Chem 402:3091–3102

    Article  CAS  Google Scholar 

  3. Public Health Research Institute (2013) Molecular beacons. http://www.molecular-beacons.org

  4. Fang X, Li JJ, Perlette J, Tan W, Wang K (2000) Molecular beacons: novel fluorescent probes. Anal Chem 72:747a–753a

    Article  CAS  Google Scholar 

  5. Tan W, Wang K, Drake TJ (2004) Molecular beacons. Curr Opin Chem Biol 8:547–553

    Article  CAS  Google Scholar 

  6. Wang K, Tang Z, Yang CJ, Kim Y, Fang X, Li W, Wu Y, Medley CD, Cao Z, Li J, Colon P, Lin H, Tan W (2008) Molecular engineering of DNA: molecular beacons. Angew Chem Int Ed 47:2–17

    Article  Google Scholar 

  7. Bao G, Rhee WJ, Tsourkas A (2009) Fluorescent probes for live-cell RNA detection. Annu Rev Biomed Eng 11:25–47

    Article  CAS  Google Scholar 

  8. Santangelo PJ (2009) Molecular beacons and related probes for intracellular RNA imaging. Nanomed Nanobiotechnol 2:11–19

    Article  Google Scholar 

  9. Armitage BA (2011) Imaging of RNA in live cells. Curr Opin Chem Biol 15:806–812

    Article  CAS  Google Scholar 

  10. Monroy-Contreras R, Vaca L (2011) Molecular beacons: powerful tools for imaging RNA in living cells. J Nucleic Acids 2011:741723

    Article  CAS  Google Scholar 

  11. Guo J, Ju J, Turro NJ (2012) Fluorescent hybridization probes for nucleic acid detection. Anal Bioanal Chem 402:3115–3125

    Article  CAS  Google Scholar 

  12. Algar WR, Massey M, Krull UJ (2009) The application of quantum dots, gold nanoparticles and molecular switches to optical nucleic-acid diagnostics. Trends Anal Chem 28:292–306

    Article  CAS  Google Scholar 

  13. Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249:505–510

    Article  CAS  Google Scholar 

  14. Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822

    Article  CAS  Google Scholar 

  15. Mascini M, Palchetti I, Tombelli S (2012) Nucleic acid and peptide aptamers: fundamentals and bioanalytical aspects. Angew Chem Int Ed 51:1316–1332

    Article  CAS  Google Scholar 

  16. Ferre-D’Amare AR, Doudna JA (1999) RNA folds: insights from recent crystal structures. Annu Rev Biophys Biomol Struct 28:57–73

    Article  Google Scholar 

  17. James W (2000) In: Meyers RA (ed) Encyclopedia of analytical chemistry. John Wiley & Sons Ltd, Chichester, pp 4848–4871

  18. Mayer G (2009) The chemical biology of aptamers. Angew Chem Int Ed 48:2672–2689

    Article  CAS  Google Scholar 

  19. Bruno JG, Carrillo MP, Phillips T, Hanson D, Bohmann JA (2011) DNA aptamer beacon assay for C-telopeptide and handheld fluorometer to monitor bone resorption. J Fluoresc 21:2021–2033

    Article  CAS  Google Scholar 

  20. Zhang JQ, Wang YS, Xue JH, He Y, Yang HX, Liang J, Shi LF, Xiao XL (2012) A gold nanoparticles-modified aptamer beacon for urinary adenosine detection based on structure-switching/fluorescence-"turning on" mechanism. J Pharm Biomed Anal 70:362–368

    Article  CAS  Google Scholar 

  21. Wu T, Biswas S, Dutta M, Stroscio MA (2011) Quantum-dot-based aptamer beacon for the detection of potassium ions. IEEE Trans Nanotechnol 10:991–995

    Article  Google Scholar 

  22. Chi CW, Lao YH, Li YS, Chen LC (2011) A quantum dot-aptamer beacon using a DNA intercalating dye as the FRET reporter: application to label-free thrombin detection. Biosens Bioelectron 15:3346–3352

    Article  CAS  Google Scholar 

  23. Tan X, Chen W, Lu S, Zhu Z, Chen T, Zhu G, You M, Tan W (2012) Molecular beacon aptamers for direct and universal quantitation of recombinant proteins from cell lysates. Anal Chem 84:8272–8276

    Article  CAS  Google Scholar 

  24. Liang Y, Zhang Z, Wei H, Hu Q, Deng J, Guo D, Cui Z, Zhang XE (2011) Aptamer beacons for visualization of endogenous protein HIV-1 reverse transcriptase in living cells. Biosens Bioelectron 28:270–276

    Article  CAS  Google Scholar 

  25. Kim JK, Choi K-J, Lee M, Jo M, Kim S (2012) Molecular imaging of a cancer-targeting theragnostics probe using a nucleolin aptamer- and microRNA-221 molecular beacon-conjugated nanoparticle. Biomaterials 33:207–217

    Article  CAS  Google Scholar 

  26. Zheng D, Seferos DS, Giljohann DA, Patel PC, Mirkin CA (2009) Aptamer nano-flares for molecular detection in living cells. Nano Lett 9:3258–3261

    Article  CAS  Google Scholar 

  27. Wang Y, Li Z, Hu D, Lin C-T, Li J, Lin Y (2010) Aptamer/graphene oxide nanocomplex for in situ molecular probing in living cells. J Am Chem Soc 132:9274–9276

    Article  CAS  Google Scholar 

  28. Nielsen LJ, Olsen LF, Ozalp VC (2010) Aptamers embedded in polyacrylamide nanoparticles: a tool for in vivo metabolite sensing. ACS Nano 4:4361–4370

    Article  CAS  Google Scholar 

  29. Tan X, Chen T, Xiong X, Mao Y, Zhu G, Yasun E, Li C, Zhu Z, Tan W (2012) Semiquantification of ATPin live cells using nonspecific desorption of DNA from grapheme oxide as the internal reference. Anal Chem 84:8622–8627

    Article  CAS  Google Scholar 

  30. Martinez K, Medley CD, Yang CJ, Tan W (2008) Investigation of the hybrid molecular probe for intracellular studies. Anal Bioanal Chem 391:983–991

    Article  CAS  Google Scholar 

  31. Juskowiak B (2011) Nucleic acid-based fluorescent probes and their analytical potential. Anal Bioanal Chem 399:3157–3176

    Article  CAS  Google Scholar 

  32. Tang Z, Mallikaratchy P, Yang R, Kim Y, Zhu Z, Wang H, Tan W (2008) Aptamer switch probe based on intramolecular displacement. J Am Chem Soc 130:11268–11269

    Article  CAS  Google Scholar 

  33. Seferos DS, Giljohann DA, Hill HD, Prigodich AE, Mirkin CA (2007) Nano-flares: probes for transfection and mRNA detection in living cells. J Am Chem Soc 129:15477–15479

    Article  CAS  Google Scholar 

  34. Tyagi S, Kramer FR (1996) Molecular beacons: probes that fluoresce upon hybridization. Nat Biotechnol 14:303–308

    Article  CAS  Google Scholar 

  35. Wu CS, Peng L, You M, Han D, Chen T, Williams KR, Yang CJ, Tan W (2012) Engineering molecular beacons for intracellular imaging. Int J Mol Imaging 2012:501579

    Google Scholar 

  36. Li JJ, Tan W (2003) A real-time assay for DNA sticky-end pairing using molecular beacons. Anal Biochem 312:251–254

    Article  CAS  Google Scholar 

  37. Wang L, Yang CJ, Medley CD, Benner SA, Tan W (2005) Locked nucleic acid molecular beacons. J Am Chem Soc 127:15664–15665

    Article  CAS  Google Scholar 

  38. Østergaard ME, Cheguru P, Papasani MR, Hill RA, Hrdlicka PJ (2010) Glowing locked nucleic acids: brightly fluorescent probes for detection of nucleic acids in cells. J Am Chem Soc 132:14221–14228

    Article  CAS  Google Scholar 

  39. Catrina IE, Marras SA, Bratu DP (2012) Tiny molecular beacons: LNA/2'-O-methyl RNA chimeric probes for imaging dynamic mRNA processes in living cells. ACS Chem Biol 7:1586–1595

    Article  CAS  Google Scholar 

  40. Wu Y, Yang CJ, Moroz LL, Tan W (2008) Nucleic acid beacons for long-term real-time intracellular monitoring. Anal Chem 80:3025–3028

    Article  CAS  Google Scholar 

  41. Dong H, Ding L, Yan F, Ji H, Ju H (2011) The use of polyethylenimine-grafted graphene nanoribbon for cellular delivery of locked nucleic acid modified molecular beacon for recognition of microRNA. Biomaterials 32:3875–3882

    Article  CAS  Google Scholar 

  42. Yang CJ, Wang L, Wu Y, Kim Y, Medley CD, Lin H, Tan W (2007) Synthesis and investigation of deoxyribonucleic acid/locked nucleic acid chimeric molecular beacons. Nucleic Acids Res 35:4030–4041

    Article  CAS  Google Scholar 

  43. Kam Y, Rubinstein A, Nissan A, Halle D, Yavin E (2012) Detection of endogenous K-ras mRNA in living cells at a single base resolution by a PNA molecular beacon. Mol Pharm 9:685–693

    Article  CAS  Google Scholar 

  44. Kummer S, Knoll A, Socher E, Bethge L, Herrmann A, Seitz O (2011) Fluorescence imaging of influenza H1N1 mRNA in living infected cells using single-chromophore FIT-PNA. Angew Chem Int Ed 50:1931–1934

    Article  CAS  Google Scholar 

  45. Swager TM (1998) The molecular wire approach to sensory signal amplification. Acc Chem Res 31:201–207

    Article  CAS  Google Scholar 

  46. Wang K, Tang Z, Yang CJ, Kim Y, Fang X, Li W, Wu Y, Medley CD, Cao Z, Li J, Colon P, Lin H, Tan W (2009) Molecular engineering of DNA: molecular beacons. Angew Chem Int Ed 48:856–870

    Article  CAS  Google Scholar 

  47. Yang CJ, Jockusch S, Vicens M, Turro NJ, Tan W (2005) Light-switching excimer probes for rapid protein monitoring in complex biological fluids. Proc Natl Acad Sci USA 102:17278–17283

    Article  CAS  Google Scholar 

  48. Wu C, Yan L, Wang C, Lin H, Wang C, Chen X, Yang CJ (2010) A general excimer signaling approach for aptamer sensors. Biosens Bioelectron 25:2232–2237

    Article  CAS  Google Scholar 

  49. Yang CJ, Lin H, Tan W (2005) Molecular assembly of superquenchers in signaling molecular interactions. J Am Chem Soc 127:12772–12773

    Article  CAS  Google Scholar 

  50. Kim Y, Yang CJ, Tan W (2007) Superior structure stability and selectivity of hairpin nucleic acid probes with an L-DNA stem. Nucleic Acids Res 35:7279–7287

    Article  CAS  Google Scholar 

  51. Ke G, Wang C, Ge Y, Zheng N, Zhu Z, Yang CJ (2012) L-DNA molecular beacon: a safe, stable, and accurate intracellular nano-thermometer for temperature sensing in living cells. J Am Chem Soc 134:18908–18911

    Article  CAS  Google Scholar 

  52. Wang C, Zhu Z, Song Y, Lin H, Yang CJ, Tan W (2011) Caged molecular beacons: controlling nucleic acid hybridization with light. Chem Commun 47:5708–5710

    Article  CAS  Google Scholar 

  53. Joshi KB, Vlachos A, Mikat V, Deller T, Heckel A (2012) Light-activatable molecular beacons with a caged loop sequence. Chem Commun 48:2746–2748

    Article  CAS  Google Scholar 

  54. Yang CJ, Martinez K, Lin H, Tan W (2006) Hybrid molecular probe for nucleic acid analysis in biological samples. J Am Chem Soc 128:9986–9987

    Article  CAS  Google Scholar 

  55. Paige JS, Nguyen-Duc T, Song W, Jaffrey SR (2012) Fluorescence imaging of cellular metabolites with RNA. Science 335:1194

    Article  CAS  Google Scholar 

  56. Villemejane J, Mir LM (2009) Physical methods of nucleic acid transfer: general concepts and applications. Br J Pharmacol 157:207–219

    Article  CAS  Google Scholar 

  57. Guo X, Huang L (2012) Recent advances in nonviral vectors for gene delivery. Acc Chem Res 45:971–979

    Article  CAS  Google Scholar 

  58. Bessodes M, Mignet N (2013) Lipids for nucleic acid delivery: synthesis and particle formation. Methods Mol Biol 948:67–84

    CAS  Google Scholar 

  59. Sokolova V, Epple M (2008) Inorganic nanoparticles as carriers of nucleic acids into cells. Angew Chem Int Ed 47:1382–1395

    Article  CAS  Google Scholar 

  60. Perlette J, Tan W (2001) Real-time monitoring of intracellular mRNA hybridization inside single living cells. Anal Chem 73:5544–5550

    Article  CAS  Google Scholar 

  61. Nitin N, Santangelo PJ, Kim G, Nie S, Bao G (2004) Peptide-linked molecular beacons for efficient delivery and rapid mRNA detection in living cells. Nucleic Acids Res 32:e58

    Article  CAS  Google Scholar 

  62. Rhee WJ, Santangelo PJ, Jo H, Bao G (2008) Target accessibility and signal specificity in live-cell detection of BMP-4 mRNA using molecular beacons. Nucleic Acids Res 36:e30

    Article  CAS  Google Scholar 

  63. Rhee WJ, Bao G (2009) Simultaneous detection of mRNA and protein stem cell markers in live cells. BMC Biotechnol 9:30

    Article  CAS  Google Scholar 

  64. Kang WJ, Cho YL, Chae JR, Lee JD, Choi KJ, Kim S (2011) Molecular beacon-based bioimaging of multiple microRNAs during myogenesis. Biomaterials 32:1915–1922

    Article  CAS  Google Scholar 

  65. Kim MY, Kim J, Hah SS (2012) Poly(A)-targeting molecular beacons: fluorescence resonance energy transfer-based in vitro quantitation and time-dependent imaging in live cells. Anal Biochem 429:92–98

    Article  CAS  Google Scholar 

  66. Yao Q, Zhang AM, Ma H, Lin S, Wang XX, Sun JG, Chen ZT (2012) Novel molecular beacons to monitor microRNAs in non-small-cell lung cancer. Mol Cell Probes 26:182–187

    Article  CAS  Google Scholar 

  67. Chen T, Wu CS, Jimenez E, Zhu Z, Dajac JG, You M, Han D, Zhang X, Tan W (2013) DNA micelle flares for intracellular mRNA imaging and gene therapy. Angew Chem Int Ed 52:2012–2016

    Article  CAS  Google Scholar 

  68. Kim E, Yang J, Park J, Kim S, Kim NH, Yook JI, Suh JS, Haam S, Huh YM (2012) Consecutive targetable smart nanoprobe for molecular recognition of cytoplasmic microRNA in metastatic breast cancer. ACS Nano 6:8525–8535

    Article  CAS  Google Scholar 

  69. Chen AK, Behlke MA, Tsourkas A (2008) Efficient cytosolic delivery of molecular beacon conjugates and flow cytometric analysis of target RNA. Nucleic Acids Res 36:e69

    Article  CAS  Google Scholar 

  70. Niidome T, Huang L (2002) Gene therapy progress and prospects: nonviral vectors. Gene Ther 9:1647–1652

    Article  CAS  Google Scholar 

  71. Jiang QY, Lai LH, Shen J, Wang QQ, Xu FJ, Tang GP (2011) Gene delivery to tumor cells by cationic polymeric nanovectors coupled to folic acid and the cell-penetrating peptide octaarginine. Biomaterials 32:7253–7262

    Article  CAS  Google Scholar 

  72. Xu ZP, Zeng QH, Lu GQ, Yu AB (2006) Inorganic nanoparticles as carriers for efficient cellular delivery. Chem Eng Sci 61:1027–1040

    Article  CAS  Google Scholar 

  73. Thomas CE, Ehrhardt A, Kay MA (2003) Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet 4:346–358

    Article  CAS  Google Scholar 

  74. Knipe JM, Peters JT, Peppas NA (2013) Theranostic agents for intracellular gene delivery with spatiotemporal imaging. Nano Today 8:21–38

    Article  CAS  Google Scholar 

  75. Liu G, Swierczewska M, Lee S, Chen X (2010) Functional nanoparticles for molecular imaging guided gene delivery. Nano Today 5:524–539

    Article  CAS  Google Scholar 

  76. Xing H, Wong NY, Xiang Y, Lu Y (2012) DNA aptamer functionalized nanomaterials for intracellular analysis, cancer cell imaging and drug delivery. Curr Opin Chem Biol 16:429–435

    Article  CAS  Google Scholar 

  77. Geszke-Moritz M, Moritz M (2013) Quantum dots as versatile probes in medical sciences: synthesis, modification and properties. Mater Sci Eng C 33:1008–1021

    Article  CAS  Google Scholar 

  78. Qi L, Gao X (2008) Emerging application of quantum dots for drug delivery and therapy. Expert Opin Drug Deliv 5(3):263–267

    Article  CAS  Google Scholar 

  79. Tsoi KM, Dai Q, Alman BA, Chan WC (2012) Are quantum dots toxic? Exploring the discrepancy between cell culture and animal studies. Acc Chem Res 46:662–671

    Article  CAS  Google Scholar 

  80. Delehanty JB, Mattoussi H, Medintz IL (2009) Delivering quantum dots into cells: strategies, progress and remaining issues. Anal Bioanal Chem 393:1091–1105

    Article  CAS  Google Scholar 

  81. Cho SJ, Maysinger D, Jain M, Roder B, Hackbarth S, Winnik FM (2007) Long-term exposure to CdTe quantum dots causes functional impairments in live cells. Langmuir 23:1974–1980

    Article  CAS  Google Scholar 

  82. Derfus AM, Chen AA, Min DH, Ruoslahti E, Bhatia SN (2007) Targeted quantum dot conjugates for siRNA delivery. Bioconjug Chem 18(5):1391–1396

    Article  CAS  Google Scholar 

  83. Chen AK, Behlke MA, Tsourkas A (2007) Avoiding false-positive signals with nuclease-vulnerable molecular beacons in single living cells. Nucleic Acids Res 35:e105

    Article  CAS  Google Scholar 

  84. Yeh HY, Yates MV, Mulchandani A, Chen W (2010) Molecular beacon-quantum dot-Au nanoparticle hybrid nanoprobes for visualizing virus replication in living cells. Chem Commun 46(22):3914–3916

    Article  CAS  Google Scholar 

  85. Papasani MR, Wang G, Hill RA (2012) Gold nanoparticles: the importance of physiological principles to devise strategies for targeted drug delivery. Nanomed Nanotechnol Biol Med 8:804–814

    Article  CAS  Google Scholar 

  86. Lévy R, Shaheen U, Cesbron Y, Sée V (2010) Gold nanoparticles delivery in mammalian live cells: a critical review. Nano Rev 1:4889

    Google Scholar 

  87. Rosi NL (2006) Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 312:1027–1030

    Article  CAS  Google Scholar 

  88. Harry SR, Hicks DJ, Amiri KI, Wright DW (2010) Hairpin DNA coated gold nanoparticles as intracellular mRNA probes for the detection of tyrosinase gene expression in melanoma cells. Chem Commun 46:5557–5559

    Article  CAS  Google Scholar 

  89. Xue J, Shan L, Chen H, Li Y, Zhu H, Deng D, Qian Z, Achilefu S, Gu Y (2013) Visual detection of STAT5B gene expression in living cell using the hairpin DNA modified gold nanoparticle beacon. Biosens Bioelectron 41:71–77

    Article  CAS  Google Scholar 

  90. Qiao G, Gao Y, Yu Z, Zhuo L, Tang B (2011) Simultaneous detection of intracellular tumor mRNA with Bi-Color imaging based on a gold nanoparticle/molecular beacon. Chem Eur J 17:11210–11215

    Article  CAS  Google Scholar 

  91. Qiao G, Zhuo L, Gao Y, Yu Z, Li N, Tang B (2011) A tumor mRNA-dependent gold nanoparticle–molecular beacon carrier for controlled drug release and intracellular imaging. Chem Commun 47:7458–7460

    Article  CAS  Google Scholar 

  92. Jayagopal A, Halfpenny KC, Perez JW, Wright DW (2010) Hairpin DNA-functionalized gold colloids for the imaging of mRNA in live cells. J Am Chem Soc 132:9789–9796

    Article  CAS  Google Scholar 

  93. Prigodich AE, Randeria PS, Briley WE, Kim NJ, Daniel WL, Giljohann DA, Mirkin CA (2012) Multiplexed nanoflares: mRNA detection in live cells. Anal Chem 84:2062–2066

    Article  CAS  Google Scholar 

  94. Wu P, Hwang K, Lan T, Lu Y (2013) A DNAzyme-gold nanoparticle probe for urnyl ion in living cells. J Am Chem Soc 135:5254–5257

    Article  CAS  Google Scholar 

  95. Conde J, Rosa J, de la Fuente JM, Baptista PV (2013) Gold-nanobeacons for simultaneous gene specific silencing and intracellular tracking of the silencing events. Biomaterials 34:2516–2523

    Article  CAS  Google Scholar 

  96. Bianco A, Prato M (2003) Can carbon nanotubes be considered useful tools for biological applications? Adv Mater 15:1765–1768

    Article  CAS  Google Scholar 

  97. Bianco A, Kostarelos K, Partidos CD, Prato M (2005) Biomedical applications of functionalised carbon nanotubes. Chem Commun 571–577

  98. Klumpp C, Kostarelos K, Prato M, Bianco A (2006) Functionalized carbon nanotubes as emerging nanovectors for the delivery of therapeutics. Biochim Biophys Acta 1758:404–412

    Article  CAS  Google Scholar 

  99. Vardharajula S, Ali SZ, Tiwari PM, Eroğlu E, Vig K, Dennis VA, Singh SR (2012) Functionalized carbon nanotubes: biomedical applications. Int J Nanomed 7:5361–5374

    CAS  Google Scholar 

  100. Wu Y, Phillips JA, Liu H, Yang R, Tan W (2008) Carbon nanotubes protect DNA strands during cellular delivery. ACS Nano 2:2023–2028

    Article  CAS  Google Scholar 

  101. Lu CH, Zhu CL, Li J, Liu JJ, Chen X, Yang HH (2010) Using graphene to protect DNA from cleavage during cellular delivery. Chem Commun 46:3116–3118

    Article  CAS  Google Scholar 

  102. Kim H, Namgung R, Singha K, Oh IK, Kim WJ (2011) Graphene oxide-polyethylenimine nanoconstruct as a gene delivery vector and bioimaging tool. Bioconjug Chem 22:2558–2567

    Article  CAS  Google Scholar 

  103. Feng L, Zhang S, Liu Z (2011) Graphene based gene transfection. Nanoscale 3:1252–1257

    Article  CAS  Google Scholar 

  104. Chung C, Kim YK, Shin D, Ryoo SR, Hong BH, Min DH (2013) Biomedical applications of graphene and graphene oxide. Acc Chem Res. doi:10.1021/ar300159f

    Google Scholar 

  105. Piao Y, Liu F, Seo TS (2012) A novel molecular beacon bearing a graphite nanoparticle as a nanoquencher for in situ mRNA detection in cancer cells. ACS Appl Mater Interfaces 4:6785–6789

    Article  CAS  Google Scholar 

  106. Kihara T, Yoshida N, Kitagawa T, Nakamura C, Nakamura N, Miyake J (2010) Development of a novel method to detect intrinsic mRNA in a living cell by using a molecular beacon-immobilized nanoneedle. Biosens Bioelectron 26:1449–1454

    Article  CAS  Google Scholar 

  107. Bates PJ, Laber DA, Miller DM, Thomas SD, Trent JO (2009) Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp Mol Pathol 86:151–164

    Article  CAS  Google Scholar 

  108. do Hwang W, Ko HY, Lee JH, Kang H, Ryu SH, Song IC, Lee DS, Kim S (2010) A nucleolin-targeted multimodal nanoparticle imaging probe for tracking cancer cells using an aptamer. J Nucl Med 51:98–105

    Article  CAS  Google Scholar 

  109. Ko HY, Choi KJ, Lee CH, Kim S (2011) A multimodal nanoparticle-based cancer imaging probe simultaneously targeting nucleolin, integrin αvβ3 and tenascin-C proteins. Biomaterials 32:1130–1138

    Article  CAS  Google Scholar 

  110. Ai J, Li T, Li B, Xu Y, Li D, Liu Z, Wang E (2012) In situ labelling and imaging of cellular protein via a bi-functional anticancer aptamer and its fluorescent ligand. Anal Chim Acta 741:93–99

    Article  CAS  Google Scholar 

  111. Kang WJ, Ko MH, Lee DS, Kim S (2009) Bioimaging of geographically adjacent proteins in a single cell by quantum dot-based fluorescent resonance energy transfer. Proteomics Clin Appl 3:1383–1388

    CAS  Google Scholar 

  112. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838

    Article  CAS  Google Scholar 

  113. Giannetti A, Tombelli S, Trono C, Ballestri M, Giambastiani G, Guerrini A, Sotgiu G, Tuci G, Varchi G, Baldini F (2013) Intracellular delivery of molecular beacons by PMMA nanoparticles and carbon nanotubes for mRNA sensing. Proc SPIE 8596:85960U

    Article  CAS  Google Scholar 

  114. Tyagi S, Alsmadi O (2004) Imaging native β-actin mRNA in motile fibroblasts. Biophys J 87:4153–4162

    Article  CAS  Google Scholar 

  115. Xiao J (2009) Single-molecule imaging in live cells. In: Hinterdorfer P, van Oijen A (eds) Handbook of single-molecule biophysics. Springer, New York, pp 43–94

    Chapter  Google Scholar 

Download references

Acknowledgments

The authors thank the regional and national institutions for the support provided by the regional project NANOCELL (PAR FAS REGIONE TOSCANA Linea 1.1.a.3) and by the national flagship project NANOMAX

Author information

Authors and Affiliations

  1. Istituto di Fisica Applicata Nello Carrara, Consiglio Nazionale delle Ricerche, Via Madonna del Piano 10, 50019, Sesto Fiorentino, Italy

    A. Giannetti, S. Tombelli & F. Baldini

Authors
  1. A. Giannetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Tombelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Baldini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. Baldini.

Additional information

Published in the topical collection Optical Nanosensing in Cells with guest editor Francesco Baldini.

A. Giannetti and S. Tombelli contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Giannetti, A., Tombelli, S. & Baldini, F. Oligonucleotide optical switches for intracellular sensing. Anal Bioanal Chem 405, 6181–6196 (2013). https://doi.org/10.1007/s00216-013-7086-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-013-7086-8

Keywords

Search

Navigation