Abstract

Imaging nanoprobes are a group of nano-sized contrast agents devised for providing improved contrast and spatial resolution for bioimaging. Among various imaging nanoprobes, optical nanoprobes capable of monitoring biological events or progresses in the cellular and molecular levels have been developed for early detection, accurate diagnosis, and personalized image-guided treatment of diseases. The optical activities of nanoprobes can be tuned on demand for specific applications by engineering their size, surface nature, morphology, and composition. In addition, by virtue of the nanostructure, nanoprobes have displayed favorable pharmacokinetic features and target specificity reflecting clinical demands. In this review, we focus on typical approaches and recent trends in development of nanoprobe-mediated optical imaging and their potential as a clinical diagnostic modality.

© 2016 Optical Society of America

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  84. A. Garcia-Uribe, T. N. Erpelding, A. Krumholz, H. Ke, K. Maslov, C. Appleton, J. A. Margenthaler, and L. V. Wang, “Dual-Modality Photoacoustic and Ultrasound Imaging System for Noninvasive Sentinel Lymph Node Detection in Patients with Breast Cancer,” Sci. Rep. 5, 15748 (2015).
    [Crossref] [PubMed]
  85. L. Bu, X. Ma, Y. Tu, B. Shen, and Z. Cheng, “Optical image-guided cancer therapy,” Curr. Pharm. Biotechnol. 14(8), 723–732 (2014).
    [Crossref] [PubMed]
  86. M. S. Murahari and M. C. Yergeri, “Identification and usage of fluorescent probes as nanoparticle contrast agents in detecting cancer,” Curr. Pharm. Des. 19(25), 4622–4640 (2013).
    [Crossref] [PubMed]
  87. J. U. Menon, P. Jadeja, P. Tambe, K. Vu, B. Yuan, and K. T. Nguyen, “Nanomaterials for photo-based diagnostic and therapeutic applications,” Theranostics 3(3), 152–166 (2013).
    [Crossref] [PubMed]
  88. S. Chapman, M. Dobrovolskaia, K. Farahani, A. Goodwin, A. Joshi, H. Lee, T. Meade, M. Pomper, K. Ptak, J. Rao, R. Singh, S. Sridhar, S. Stern, A. Wang, J. B. Weaver, G. Woloschak, and L. Yang, “Nanoparticles for cancer imaging: The good, the bad, and the promise,” Nano Today 8(5), 454–460 (2013).
    [Crossref] [PubMed]
  89. H. G. van der Poel, T. Buckle, O. R. Brouwer, R. A. Valdés Olmos, and F. W. van Leeuwen, “Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodal tracer,” Eur. Urol. 60(4), 826–833 (2011).
    [Crossref] [PubMed]
  90. O. R. Brouwer, W. M. Klop, T. Buckle, L. Vermeeren, M. W. van den Brekel, A. J. Balm, O. E. Nieweg, R. A. Valdés Olmos, and F. W. van Leeuwen, “Feasibility of sentinel node biopsy in head and neck melanoma using a hybrid radioactive and fluorescent tracer,” Ann. Surg. Oncol. 19(6), 1988–1994 (2012).
    [Crossref] [PubMed]
  91. B. E. Schaafsma, F. P. Verbeek, D. D. Rietbergen, B. van der Hiel, J. R. van der Vorst, G. J. Liefers, J. V. Frangioni, C. J. van de Velde, F. W. van Leeuwen, and A. L. Vahrmeijer, “Clinical trial of combined radio- and fluorescence-guided sentinel lymph node biopsy in breast cancer,” Br. J. Surg. 100(8), 1037–1044 (2013).
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  92. E. Phillips, O. Penate-Medina, P. B. Zanzonico, R. D. Carvajal, P. Mohan, Y. Ye, J. Humm, M. Gönen, H. Kalaigian, H. Schöder, H. W. Strauss, S. M. Larson, U. Wiesner, and M. S. Bradbury, “Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe,” Sci. Transl. Med. 6(260), 260ra149 (2014).
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2016 (2)

J. Heo, C.-K. Lim, Y. Kim, H.-J. Cho, Y.-D. Lee, J. H. Maeng, D.-R. Ahn, S. Lee, J. Bang, S. Y. Park, and S. Kim, “Fluorogenic nanoreactor assembly with boosted sensing kinetics for timely imaging of cellular hydrogen peroxide,” Chem. Commun. (Camb.) 52(6), 1131–1134 (2016).
[Crossref] [PubMed]

D. H. Ortgies, L. de la Cueva, B. Del Rosal, F. Sanz-Rodríguez, N. Fernández, M. C. Iglesias-de la Cruz, G. Salas, D. Cabrera, F. J. Teran, D. Jaque, and E. Martín Rodríguez, “In vivo deep tissue fluorescence and magnetic imaging employing hybrid nanostructures,” ACS Appl. Mater. Interfaces 8(2), 1406–1414 (2016).
[Crossref] [PubMed]

2015 (8)

K. Miki, T. Inoue, Y. Kobayashi, K. Nakano, H. Matsuoka, F. Yamauchi, T. Yano, and K. Ohe, “Near-infrared dye-conjugated amphiphilic hyaluronic acid derivatives as a dual contrast agent for in vivo optical and photoacoustic tumor imaging,” Biomacromolecules 16(1), 219–227 (2015).
[Crossref] [PubMed]

Z. Liu, P. Rong, L. Yu, X. Zhang, C. Yang, F. Guo, Y. Zhao, K. Zhou, W. Wang, and W. Zeng, “Dual-Modality Noninvasive Mapping of Sentinel Lymph Node by Photoacoustic and Near-Infrared Fluorescent Imaging Using Dye-Loaded Mesoporous Silica Nanoparticles,” Mol. Pharm. 12(9), 3119–3128 (2015).
[Crossref] [PubMed]

W. Guo, X. Sun, O. Jacobson, X. Yan, K. Min, A. Srivatsan, G. Niu, D. O. Kiesewetter, J. Chang, and X. Chen, “Intrinsically radioactive [64Cu]CuInS/ZnS quantum dots for PET and optical imaging: improved radiochemical stability and controllable Cerenkov luminescence,” ACS Nano 9(1), 488–495 (2015).
[Crossref] [PubMed]

A. Singh, Y. H. Seo, C. K. Lim, J. Koh, W. D. Jang, I. C. Kwon, and S. Kim, “Biolighted Nanotorch Capable of Systemic Self-Delivery and Diagnostic Imaging,” ACS Nano 9(10), 9906–9911 (2015).

O. S. Wolfbeis, “An overview of nanoparticles commonly used in fluorescent bioimaging,” Chem. Soc. Rev. 44(14), 4743–4768 (2015).
[Crossref] [PubMed]

Y. H. Seo, M. J. Cho, O. J. Cheong, W.-D. Jang, T. Y. Ohulchanskyy, S. Lee, D. H. Choi, P. N. Prasad, and S. Kim, “Low-bandgap biophotonic nanoblend: a platform for systemic disease targeting and functional imaging,” Biomaterials 39, 225–233 (2015).
[Crossref] [PubMed]

H. S. Choi, Y. Kim, J. C. Park, M. H. Oh, D. Y. Jeon, and Y. S. Nam, “Highly luminescent, off-stoichiometric CuxInyS2/ZnS quantum dots for near-infrared fluorescence bio-imaging,” RSC Advances 5(54), 43449–43455 (2015).
[Crossref]

A. Garcia-Uribe, T. N. Erpelding, A. Krumholz, H. Ke, K. Maslov, C. Appleton, J. A. Margenthaler, and L. V. Wang, “Dual-Modality Photoacoustic and Ultrasound Imaging System for Noninvasive Sentinel Lymph Node Detection in Patients with Breast Cancer,” Sci. Rep. 5, 15748 (2015).
[Crossref] [PubMed]

2014 (11)

L. Bu, X. Ma, Y. Tu, B. Shen, and Z. Cheng, “Optical image-guided cancer therapy,” Curr. Pharm. Biotechnol. 14(8), 723–732 (2014).
[Crossref] [PubMed]

E. Phillips, O. Penate-Medina, P. B. Zanzonico, R. D. Carvajal, P. Mohan, Y. Ye, J. Humm, M. Gönen, H. Kalaigian, H. Schöder, H. W. Strauss, S. M. Larson, U. Wiesner, and M. S. Bradbury, “Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe,” Sci. Transl. Med. 6(260), 260ra149 (2014).
[Crossref] [PubMed]

A. J. Shuhendler, K. Pu, L. Cui, J. P. Uetrecht, and J. Rao, “Real-time imaging of oxidative and nitrosative stress in the liver of live animals for drug-toxicity testing,” Nat. Biotechnol. 32(4), 373–380 (2014).
[Crossref] [PubMed]

G. Chen, H. Qiu, P. N. Prasad, and X. Chen, “Upconversion nanoparticles: design, nanochemistry, and applications in theranostics,” Chem. Rev. 114(10), 5161–5214 (2014).
[Crossref] [PubMed]

A. Ray, A. Mukundan, Z. Xie, L. Karamchand, X. Wang, and R. Kopelman, “Highly stable polymer coated nano-clustered silver plates: a multimodal optical contrast agent for biomedical imaging,” Nanotechnology 25(44), 445104 (2014).
[Crossref] [PubMed]

L. Xi, M. Satpathy, Q. Zhao, W. Qian, L. Yang, and H. Jiang, “HER-2/neu targeted delivery of a nanoprobe enables dual photoacoustic and fluorescence tomography of ovarian cancer,” Nanomedicine (Lond.) 10(3), 669–677 (2014).
[PubMed]

Z. Sheng, D. Hu, M. Zheng, P. Zhao, H. Liu, D. Gao, P. Gong, G. Gao, P. Zhang, Y. Ma, and L. Cai, “Smart human serum albumin-indocyanine green nanoparticles generated by programmed assembly for dual-modal imaging-guided cancer synergistic phototherapy,” ACS Nano 8(12), 12310–12322 (2014).
[Crossref] [PubMed]

D. Zhang, Y. X. Zhao, Z. Y. Qiao, U. Mayerhöffer, P. Spenst, X. J. Li, F. Würthner, and H. Wang, “Nano-confined squaraine dye assemblies: new photoacoustic and near-infrared fluorescence dual-modular imaging probes in vivo,” Bioconjug. Chem. 25(11), 2021–2029 (2014).
[Crossref] [PubMed]

K. C. Black, Y. Wang, H. P. Luehmann, X. Cai, W. Xing, B. Pang, Y. Zhao, C. S. Cutler, L. V. Wang, Y. Liu, and Y. Xia, “Radioactive 198Au-doped nanostructures with different shapes for in vivo analyses of their biodistribution, tumor uptake, and intratumoral distribution,” ACS Nano 8(5), 4385–4394 (2014).
[Crossref] [PubMed]

X. Sun, X. Huang, J. Guo, W. Zhu, Y. Ding, G. Niu, A. Wang, D. O. Kiesewetter, Z. L. Wang, S. Sun, and X. Chen, “Self-illuminating 64Cu-doped CdSe/ZnS nanocrystals for in vivo tumor imaging,” J. Am. Chem. Soc. 136(5), 1706–1709 (2014).
[Crossref] [PubMed]

E. S. Jang, S. Y. Lee, E. J. Cha, I. C. Sun, I. C. Kwon, D. Kim, Y. I. Kim, K. Kim, and C. H. Ahn, “Fluorescent dye labeled iron oxide/silica core/shell nanoparticle as a multimodal imaging probe,” Pharm. Res. 31(12), 3371–3378 (2014).
[Crossref] [PubMed]

2013 (14)

Y. Wang, Y. Liu, H. Luehmann, X. Xia, D. Wan, C. Cutler, and Y. Xia, “Radioluminescent gold nanocages with controlled radioactivity for real-time in vivo imaging,” Nano Lett. 13(2), 581–585 (2013).
[Crossref] [PubMed]

S. Ahmed, J. Dong, M. Yui, T. Kato, J. Lee, and E. Y. Park, “Quantum dots incorporated magnetic nanoparticles for imaging colon carcinoma cells,” J. Nanobiotechnology 11(1), 28 (2013).
[Crossref] [PubMed]

X. Liu, C. Lee, W.-C. Law, D. Zhu, M. Liu, M. Jeon, J. Kim, P. N. Prasad, C. Kim, and M. T. Swihart, “Au-Cu2-xSe heterodimer nanoparticles with broad localized surface plasmon resonance as contrast agents for deep tissue imaging,” Nano Lett. 13(9), 4333–4339 (2013).
[Crossref] [PubMed]

Q. Liu, B. Yin, T. Yang, Y. Yang, Z. Shen, P. Yao, and F. Li, “A general strategy for biocompatible, high-effective upconversion nanocapsules based on triplet-triplet annihilation,” J. Am. Chem. Soc. 135(13), 5029–5037 (2013).
[Crossref] [PubMed]

D. Lee, S. Bae, Q. Ke, J. Lee, B. Song, S. A. Karumanchi, G. Khang, H. S. Choi, and P. M. Kang, “Hydrogen peroxide-responsive copolyoxalate nanoparticles for detection and therapy of ischemia-reperfusion injury,” J. Control. Release 172(3), 1102–1110 (2013).
[Crossref] [PubMed]

A. Singh, C. K. Lim, Y.-D. Lee, J. H. Maeng, S. Lee, J. Koh, and S. Kim, “Tuning solid-state fluorescence to the near-infrared: a combinatorial approach to discovering molecular nanoprobes for biomedical imaging,” ACS Appl. Mater. Interfaces 5(18), 8881–8888 (2013).
[Crossref] [PubMed]

M. G. Panthani, T. A. Khan, D. K. Reid, D. J. Hellebusch, M. R. Rasch, J. A. Maynard, and B. A. Korgel, “In vivo whole animal fluorescence imaging of a microparticle-based oral vaccine containing (CuInSexS2-x)/ZnS core/shell quantum dots,” Nano Lett. 13(9), 4294–4298 (2013).
[Crossref] [PubMed]

L. Gu, D. J. Hall, Z. Qin, E. Anglin, J. Joo, D. J. Mooney, S. B. Howell, and M. J. Sailor, “In vivo time-gated fluorescence imaging with biodegradable luminescent porous silicon nanoparticles,” Nat. Commun. 4, 2326–2333 (2013).
[Crossref] [PubMed]

C. Wu and D. T. Chiu, “Highly fluorescent semiconducting polymer dots for biology and medicine,” Angew. Chem. Int. Ed. Engl. 52(11), 3086–3109 (2013).
[Crossref] [PubMed]

B. E. Schaafsma, F. P. Verbeek, D. D. Rietbergen, B. van der Hiel, J. R. van der Vorst, G. J. Liefers, J. V. Frangioni, C. J. van de Velde, F. W. van Leeuwen, and A. L. Vahrmeijer, “Clinical trial of combined radio- and fluorescence-guided sentinel lymph node biopsy in breast cancer,” Br. J. Surg. 100(8), 1037–1044 (2013).
[Crossref] [PubMed]

M. S. Murahari and M. C. Yergeri, “Identification and usage of fluorescent probes as nanoparticle contrast agents in detecting cancer,” Curr. Pharm. Des. 19(25), 4622–4640 (2013).
[Crossref] [PubMed]

J. U. Menon, P. Jadeja, P. Tambe, K. Vu, B. Yuan, and K. T. Nguyen, “Nanomaterials for photo-based diagnostic and therapeutic applications,” Theranostics 3(3), 152–166 (2013).
[Crossref] [PubMed]

S. Chapman, M. Dobrovolskaia, K. Farahani, A. Goodwin, A. Joshi, H. Lee, T. Meade, M. Pomper, K. Ptak, J. Rao, R. Singh, S. Sridhar, S. Stern, A. Wang, J. B. Weaver, G. Woloschak, and L. Yang, “Nanoparticles for cancer imaging: The good, the bad, and the promise,” Nano Today 8(5), 454–460 (2013).
[Crossref] [PubMed]

D. M. Gilmore, O. V. Khullar, M. T. Jaklitsch, L. R. Chirieac, J. V. Frangioni, and Y. L. Colson, “Identification of metastatic nodal disease in a phase 1 dose-escalation trial of intraoperative sentinel lymph node mapping in non-small cell lung cancer using near-infrared imaging,” J. Thorac. Cardiovasc. Surg. 146(3), 562(2013).
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2012 (10)

N. Yokoyama, T. Otani, H. Hashidate, C. Maeda, T. Katada, N. Sudo, S. Manabe, Y. Ikeno, A. Toyoda, and N. Katayanagi, “Real-time detection of hepatic micrometastases from pancreatic cancer by intraoperative fluorescence imaging: preliminary results of a prospective study,” Cancer 118(11), 2813–2819 (2012).
[Crossref] [PubMed]

S. P. Lerner, H. Liu, M. F. Wu, Y. K. Thomas, and J. A. Witjes, “Fluorescence and white light cystoscopy for detection of carcinoma in situ of the urinary bladder,” Urol. Oncol. 30(3), 285–289 (2012).
[Crossref] [PubMed]

O. R. Brouwer, W. M. Klop, T. Buckle, L. Vermeeren, M. W. van den Brekel, A. J. Balm, O. E. Nieweg, R. A. Valdés Olmos, and F. W. van Leeuwen, “Feasibility of sentinel node biopsy in head and neck melanoma using a hybrid radioactive and fluorescent tracer,” Ann. Surg. Oncol. 19(6), 1988–1994 (2012).
[Crossref] [PubMed]

M. Heijblom, D. Piras, W. Xia, J. C. G. van Hespen, J. M. Klaase, F. M. van den Engh, T. G. van Leeuwen, W. Steenbergen, and S. Manohar, “Visualizing breast cancer using the twente photoacoustic mammoscope: What do we learn from twelve new patient measurements?” Opt. Express 20(11), 11582–11597 (2012).
[Crossref] [PubMed]

D. E. Lee, H. Koo, I. C. Sun, J. H. Ryu, K. Kim, and I. C. Kwon, “Multifunctional nanoparticles for multimodal imaging and theragnosis,” Chem. Soc. Rev. 41(7), 2656–2672 (2012).
[Crossref] [PubMed]

L. Ye, K.-T. Yong, L. Liu, I. Roy, R. Hu, J. Zhu, H. Cai, W.-C. Law, J. Liu, K. Wang, J. Liu, Y. Liu, Y. Hu, X. Zhang, M. T. Swihart, and P. N. Prasad, “A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots,” Nat. Nanotechnol. 7(7), 453–458 (2012).
[Crossref] [PubMed]

G. Chen, J. Shen, T. Y. Ohulchanskyy, N. J. Patel, A. Kutikov, Z. Li, J. Song, R. K. Pandey, H. Agren, P. N. Prasad, and G. Han, “(α-NaYbF4:Tm3+)/CaF2 core/shell nanoparticles with efficient near-infrared to near-infrared upconversion for high-contrast deep tissue bioimaging,” ACS Nano 6(9), 8280–8287 (2012).
[Crossref] [PubMed]

Y.-D. Lee, C.-K. Lim, A. Singh, J. Koh, J. Kim, I. C. Kwon, and S. Kim, “Dye/peroxalate aggregated nanoparticles with enhanced and tunable chemiluminescence for biomedical imaging of hydrogen peroxide,” ACS Nano 6(8), 6759–6766 (2012).
[Crossref] [PubMed]

Z. Zhang, L. Wang, J. Wang, X. Jiang, X. Li, Z. Hu, Y. Ji, X. Wu, and C. Chen, “Mesoporous silica-coated gold nanorods as a light-mediated multifunctional theranostic platform for cancer treatment,” Adv. Mater. 24(11), 1418–1423 (2012).
[Crossref] [PubMed]

A. Taruttis and V. Ntziachristos, “Translational optical imaging,” AJR Am. J. Roentgenol. 199(2), 263–271 (2012).
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2011 (8)

J. F. Lovell, C. S. Jin, E. Huynh, H. Jin, C. Kim, J. L. Rubinstein, W. C. Chan, W. Cao, L. V. Wang, and G. Zheng, “Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents,” Nat. Mater. 10(4), 324–332 (2011).
[Crossref] [PubMed]

M. Benezra, O. Penate-Medina, P. B. Zanzonico, D. Schaer, H. Ow, A. Burns, E. DeStanchina, V. Longo, E. Herz, S. Iyer, J. Wolchok, S. M. Larson, U. Wiesner, and M. S. Bradbury, “Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma,” J. Clin. Invest. 121(7), 2768–2780 (2011).
[Crossref] [PubMed]

J. Yao and L. V. Wang, “Photoacoustic tomography: fundamentals, advances and prospects,” Contrast Media Mol. Imaging 6(5), 332–345 (2011).
[Crossref] [PubMed]

P. Beard, “Biomedical photoacoustic imaging,” Interface Focus 1(4), 602–631 (2011).
[Crossref] [PubMed]

L. M. Crane, G. Themelis, H. J. Arts, K. T. Buddingh, A. H. Brouwers, V. Ntziachristos, G. M. van Dam, and A. G. van der Zee, “Intraoperative near-infrared fluorescence imaging for sentinel lymph node detection in vulvar cancer: first clinical results,” Gynecol. Oncol. 120(2), 291–295 (2011).
[Crossref] [PubMed]

G. G. Hermann, K. Mogensen, S. Carlsson, N. Marcussen, and S. Duun, “Fluorescence-guided transurethral resection of bladder tumours reduces bladder tumour recurrence due to less residual tumour tissue in Ta/T1 patients: a randomized two-centre study,” BJU Int. 108(8b), E297–E303 (2011).
[Crossref] [PubMed]

H. G. van der Poel, T. Buckle, O. R. Brouwer, R. A. Valdés Olmos, and F. W. van Leeuwen, “Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodal tracer,” Eur. Urol. 60(4), 826–833 (2011).
[Crossref] [PubMed]

L. M. Crane, G. Themelis, R. G. Pleijhuis, N. J. Harlaar, A. Sarantopoulos, H. J. Arts, A. G. van der Zee, V. Ntziachristos, and G. M. van Dam, “Intraoperative multispectral fluorescence imaging for the detection of the sentinel lymph node in cervical cancer: a novel concept,” Mol. Imaging Biol. 13(5), 1043–1049 (2011).
[Crossref] [PubMed]

2010 (10)

C.-K. Lim, Y.-D. Lee, J. Na, J. M. Oh, S. Her, K. Kim, K. Choi, S. Kim, and I. C. Kwon, “Chemiluminescence-generating nanoreactor formulation for near-infrared imaging of hydrogen peroxide and glucose level in vivo,” Adv. Funct. Mater. 20(16), 2644–2648 (2010).
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L. Xiong, T. Yang, Y. Yang, C. Xu, and F. Li, “Long-term in vivo biodistribution imaging and toxicity of polyacrylic acid-coated upconversion nanophosphors,” Biomaterials 31(27), 7078–7085 (2010).
[Crossref] [PubMed]

P. Pantazis, J. Maloney, D. Wu, and S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
[Crossref] [PubMed]

B. E. Cohen, “Biological imaging: beyond fluorescence,” Nature 467(7314), 407–408 (2010).
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X. He, J. Gao, S. S. Gambhir, and Z. Cheng, “Near-infrared fluorescent nanoprobes for cancer molecular imaging: status and challenges,” Trends Mol. Med. 16(12), 574–583 (2010).
[Crossref] [PubMed]

S. Kim, C.-K. Lim, J. Na, Y.-D. Lee, K. Kim, K. Choi, J. F. Leary, and I. C. Kwon, “Conjugated polymer nanoparticles for biomedical in vivo imaging,” Chem. Commun. (Camb.) 46(10), 1617–1619 (2010).
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R. Kumar, I. Roy, T. Y. Ohulchanskky, L. A. Vathy, E. J. Bergey, M. Sajjad, and P. N. Prasad, “In vivo biodistribution and clearance studies using multimodal organically modified silica nanoparticles,” ACS Nano 4(2), 699–708 (2010).
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W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
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J. Chen, C. Glaus, R. Laforest, Q. Zhang, M. Yang, M. Gidding, M. J. Welch, and Y. Xia, “Gold nanocages as photothermal transducers for cancer treatment,” Small 6(7), 811–817 (2010).
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A. de la Zerda, Z. Liu, S. Bodapati, R. Teed, S. Vaithilingam, B. T. Khuri-Yakub, X. Chen, H. Dai, and S. S. Gambhir, “Ultrahigh sensitivity carbon nanotube agents for photoacoustic molecular imaging in living mice,” Nano Lett. 10(6), 2168–2172 (2010).
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2009 (10)

J.-W. Kim, E. I. Galanzha, E. V. Shashkov, H.-M. Moon, and V. P. Zharov, “Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents,” Nat. Nanotechnol. 4(10), 688–694 (2009).
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R. Robertson, M. S. Germanos, C. Li, G. S. Mitchell, S. R. Cherry, and M. D. Silva, “Optical imaging of Cerenkov light generation from positron-emitting radiotracers,” Phys. Med. Biol. 54(16), N355–N365 (2009).
[Crossref] [PubMed]

S. Lee and X. Chen, “Dual-modality probes for in vivo molecular imaging,” Mol. Imaging 8(2), 87–100 (2009).
[PubMed]

S. Santra, C. Kaittanis, J. Grimm, and J. M. Perez, “Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging,” Small 5(16), 1862–1868 (2009).
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A. M. Smith, M. C. Mancini, and S. Nie, “Bioimaging: second window for in vivo imaging,” Nat. Nanotechnol. 4(11), 710–711 (2009).
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K.-T. Yong, H. Ding, I. Roy, W.-C. Law, E. J. Bergey, A. Maitra, and P. N. Prasad, “Imaging Pancreatic Cancer Using Bioconjugated InP Quantum Dots,” ACS Nano 3(3), 502–510 (2009).
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L. Li, T. J. Daou, I. Texier, T. T. Kim Chi, N. Q. Liem, and P. Reiss, “Highly luminescent CuInS2/ZnS core/shell nanocrystals: cadmium-free quantum dots for in vivo imaging,” Chem. Mater. 21(12), 2422–2429 (2009).
[Crossref]

S. Mallidi, T. Larson, J. Tam, P. P. Joshi, A. Karpiouk, K. Sokolov, and S. Emelianov, “Multiwavelength photoacoustic imaging and plasmon resonance coupling of gold nanoparticles for selective detection of cancer,” Nano Lett. 9(8), 2825–2831 (2009).
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S. L. Troyan, V. Kianzad, S. L. Gibbs-Strauss, S. Gioux, A. Matsui, R. Oketokoun, L. Ngo, A. Khamene, F. Azar, and J. V. Frangioni, “The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping,” Ann. Surg. Oncol. 16(10), 2943–2952 (2009).
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T. Ishizawa, N. Fukushima, J. Shibahara, K. Masuda, S. Tamura, T. Aoki, K. Hasegawa, Y. Beck, M. Fukayama, and N. Kokudo, “Real-time identification of liver cancers by using indocyanine green fluorescent imaging,” Cancer 115(11), 2491–2504 (2009).
[Crossref] [PubMed]

2008 (4)

N. Tagaya, R. Yamazaki, A. Nakagawa, A. Abe, K. Hamada, K. Kubota, and T. Oyama, “Intraoperative identification of sentinel lymph nodes by near-infrared fluorescence imaging in patients with breast cancer,” Am. J. Surg. 195(6), 850–853 (2008).
[Crossref] [PubMed]

M. Nyk, R. Kumar, T. Y. Ohulchanskyy, E. J. Bergey, and P. N. Prasad, “High contrast in vitro and in vivo photoluminescence bioimaging using near infrared to near infrared up-conversion in Tm3+ and Yb3+ doped fluoride nanophosphors,” Nano Lett. 8(11), 3834–3838 (2008).
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2007 (5)

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2006 (1)

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2005 (1)

T. Kitai, T. Inomoto, M. Miwa, and T. Shikayama, “Fluorescence navigation with indocyanine green for detecting sentinel lymph nodes in breast cancer,” Breast Cancer 12(3), 211–215 (2005).
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2004 (1)

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2003 (2)

M. F. Kircher, U. Mahmood, R. S. King, R. Weissleder, and L. Josephson, “A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation,” Cancer Res. 63(23), 8122–8125 (2003).
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2000 (1)

S. Raha and B. H. Robinson, “Mitochondria, oxygen free radicals, disease and ageing,” Trends Biochem. Sci. 25(10), 502–508 (2000).
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1955 (1)

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K. C. Black, Y. Wang, H. P. Luehmann, X. Cai, W. Xing, B. Pang, Y. Zhao, C. S. Cutler, L. V. Wang, Y. Liu, and Y. Xia, “Radioactive 198Au-doped nanostructures with different shapes for in vivo analyses of their biodistribution, tumor uptake, and intratumoral distribution,” ACS Nano 8(5), 4385–4394 (2014).
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Bodapati, S.

A. de la Zerda, Z. Liu, S. Bodapati, R. Teed, S. Vaithilingam, B. T. Khuri-Yakub, X. Chen, H. Dai, and S. S. Gambhir, “Ultrahigh sensitivity carbon nanotube agents for photoacoustic molecular imaging in living mice,” Nano Lett. 10(6), 2168–2172 (2010).
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E. Phillips, O. Penate-Medina, P. B. Zanzonico, R. D. Carvajal, P. Mohan, Y. Ye, J. Humm, M. Gönen, H. Kalaigian, H. Schöder, H. W. Strauss, S. M. Larson, U. Wiesner, and M. S. Bradbury, “Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe,” Sci. Transl. Med. 6(260), 260ra149 (2014).
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W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
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O. R. Brouwer, W. M. Klop, T. Buckle, L. Vermeeren, M. W. van den Brekel, A. J. Balm, O. E. Nieweg, R. A. Valdés Olmos, and F. W. van Leeuwen, “Feasibility of sentinel node biopsy in head and neck melanoma using a hybrid radioactive and fluorescent tracer,” Ann. Surg. Oncol. 19(6), 1988–1994 (2012).
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H. G. van der Poel, T. Buckle, O. R. Brouwer, R. A. Valdés Olmos, and F. W. van Leeuwen, “Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodal tracer,” Eur. Urol. 60(4), 826–833 (2011).
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L. M. Crane, G. Themelis, H. J. Arts, K. T. Buddingh, A. H. Brouwers, V. Ntziachristos, G. M. van Dam, and A. G. van der Zee, “Intraoperative near-infrared fluorescence imaging for sentinel lymph node detection in vulvar cancer: first clinical results,” Gynecol. Oncol. 120(2), 291–295 (2011).
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L. Bu, X. Ma, Y. Tu, B. Shen, and Z. Cheng, “Optical image-guided cancer therapy,” Curr. Pharm. Biotechnol. 14(8), 723–732 (2014).
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O. R. Brouwer, W. M. Klop, T. Buckle, L. Vermeeren, M. W. van den Brekel, A. J. Balm, O. E. Nieweg, R. A. Valdés Olmos, and F. W. van Leeuwen, “Feasibility of sentinel node biopsy in head and neck melanoma using a hybrid radioactive and fluorescent tracer,” Ann. Surg. Oncol. 19(6), 1988–1994 (2012).
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H. G. van der Poel, T. Buckle, O. R. Brouwer, R. A. Valdés Olmos, and F. W. van Leeuwen, “Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodal tracer,” Eur. Urol. 60(4), 826–833 (2011).
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L. M. Crane, G. Themelis, H. J. Arts, K. T. Buddingh, A. H. Brouwers, V. Ntziachristos, G. M. van Dam, and A. G. van der Zee, “Intraoperative near-infrared fluorescence imaging for sentinel lymph node detection in vulvar cancer: first clinical results,” Gynecol. Oncol. 120(2), 291–295 (2011).
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M. Benezra, O. Penate-Medina, P. B. Zanzonico, D. Schaer, H. Ow, A. Burns, E. DeStanchina, V. Longo, E. Herz, S. Iyer, J. Wolchok, S. M. Larson, U. Wiesner, and M. S. Bradbury, “Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma,” J. Clin. Invest. 121(7), 2768–2780 (2011).
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W. Cai and X. Chen, “Nanoplatforms for targeted molecular imaging in living subjects,” Small 3(11), 1840–1854 (2007).
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K. C. Black, Y. Wang, H. P. Luehmann, X. Cai, W. Xing, B. Pang, Y. Zhao, C. S. Cutler, L. V. Wang, Y. Liu, and Y. Xia, “Radioactive 198Au-doped nanostructures with different shapes for in vivo analyses of their biodistribution, tumor uptake, and intratumoral distribution,” ACS Nano 8(5), 4385–4394 (2014).
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J. F. Lovell, C. S. Jin, E. Huynh, H. Jin, C. Kim, J. L. Rubinstein, W. C. Chan, W. Cao, L. V. Wang, and G. Zheng, “Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents,” Nat. Mater. 10(4), 324–332 (2011).
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E. S. Jang, S. Y. Lee, E. J. Cha, I. C. Sun, I. C. Kwon, D. Kim, Y. I. Kim, K. Kim, and C. H. Ahn, “Fluorescent dye labeled iron oxide/silica core/shell nanoparticle as a multimodal imaging probe,” Pharm. Res. 31(12), 3371–3378 (2014).
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W. Guo, X. Sun, O. Jacobson, X. Yan, K. Min, A. Srivatsan, G. Niu, D. O. Kiesewetter, J. Chang, and X. Chen, “Intrinsically radioactive [64Cu]CuInS/ZnS quantum dots for PET and optical imaging: improved radiochemical stability and controllable Cerenkov luminescence,” ACS Nano 9(1), 488–495 (2015).
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L. Bu, X. Ma, Y. Tu, B. Shen, and Z. Cheng, “Optical image-guided cancer therapy,” Curr. Pharm. Biotechnol. 14(8), 723–732 (2014).
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J. F. Lovell, C. S. Jin, E. Huynh, H. Jin, C. Kim, J. L. Rubinstein, W. C. Chan, W. Cao, L. V. Wang, and G. Zheng, “Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents,” Nat. Mater. 10(4), 324–332 (2011).
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X. Liu, C. Lee, W.-C. Law, D. Zhu, M. Liu, M. Jeon, J. Kim, P. N. Prasad, C. Kim, and M. T. Swihart, “Au-Cu2-xSe heterodimer nanoparticles with broad localized surface plasmon resonance as contrast agents for deep tissue imaging,” Nano Lett. 13(9), 4333–4339 (2013).
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D. E. Lee, H. Koo, I. C. Sun, J. H. Ryu, K. Kim, and I. C. Kwon, “Multifunctional nanoparticles for multimodal imaging and theragnosis,” Chem. Soc. Rev. 41(7), 2656–2672 (2012).
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Y. H. Seo, M. J. Cho, O. J. Cheong, W.-D. Jang, T. Y. Ohulchanskyy, S. Lee, D. H. Choi, P. N. Prasad, and S. Kim, “Low-bandgap biophotonic nanoblend: a platform for systemic disease targeting and functional imaging,” Biomaterials 39, 225–233 (2015).
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A. Singh, Y. H. Seo, C. K. Lim, J. Koh, W. D. Jang, I. C. Kwon, and S. Kim, “Biolighted Nanotorch Capable of Systemic Self-Delivery and Diagnostic Imaging,” ACS Nano 9(10), 9906–9911 (2015).

A. Singh, C. K. Lim, Y.-D. Lee, J. H. Maeng, S. Lee, J. Koh, and S. Kim, “Tuning solid-state fluorescence to the near-infrared: a combinatorial approach to discovering molecular nanoprobes for biomedical imaging,” ACS Appl. Mater. Interfaces 5(18), 8881–8888 (2013).
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Y.-D. Lee, C.-K. Lim, A. Singh, J. Koh, J. Kim, I. C. Kwon, and S. Kim, “Dye/peroxalate aggregated nanoparticles with enhanced and tunable chemiluminescence for biomedical imaging of hydrogen peroxide,” ACS Nano 6(8), 6759–6766 (2012).
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A. Singh, C. K. Lim, Y.-D. Lee, J. H. Maeng, S. Lee, J. Koh, and S. Kim, “Tuning solid-state fluorescence to the near-infrared: a combinatorial approach to discovering molecular nanoprobes for biomedical imaging,” ACS Appl. Mater. Interfaces 5(18), 8881–8888 (2013).
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Figures (11)

Fig. 1
Fig. 1 a) Schematic diagram of SSF-based NIR-emitting micellar nanoprobe and HOMO/LUMO electron distributions of the loaded dye. b) FL spectra of the dye in THF solution (dotted) and in self-aggregated NP dispersion (10% v/v THF in DW, solid) with corresponding NIR fluorescence imaging. c) FL images of a SCC7 tumor-bearing mouse after intravenous administration of the probe (left, red arrow indicates tumor region) and pseudo-color image at 12 h post-injection with FL spectra for tissue and tumor (upper right corner) and corresponding fluorescence intensity (lower right corner). (reprinted with permission from [9], ©2013 American Chemical Society)
Fig. 2
Fig. 2 a) Molecular structures of constituents of a RNS-responsive FRET-based nanoprobe (the first, second and third quadrants) and its schematic diagram for RNS sensing mechanism (the fourth quadrant). b) Ratiometric change in FL spectrum of the same probe with respect to ONOO- concentration. c) FL images of hepatotoxicity-induced mice (by intraperitoneal administration of anti-pyretic acetaminophen, APAP) followed by intravenous administration of the same probe. (Reprinted by permission from Macmillan Publishers Ltd, Nature Biotechnology [19], ©2014)
Fig. 3
Fig. 3 a) Optical spectra and b) TEM images of α-(NaYbF4:0.5% Tm3+)/CaF2 core/shell UCNPs. c) Merged upconversion FL (980-nm laser excitation) and bright-field image of a cuvette filled with the same UCNPs under pork tissue (left) and bright-field image of the pork tissue in a side view (right). d) Upconversion FL (980-nm laser excitation, left) and merged (right) images of a BALB/c mouse injected intravenously with the same UCNPs coated by hyaluronic acid. (Reprinted from permission from [26], ©2010 American Chemical Society)
Fig. 4
Fig. 4 a) Schematic diagram of the peroxalate-backboned polymer nanoparticle as a ROS-activated CL nanoprobe. b) In vivo CL imaging of peritoneal inflammatory model after administration of CL nanoprobe. (Reprinted by permission from Macmillan Publishers Ltd, Nature Materials [31], ©2007)
Fig. 5
Fig. 5 a) Schematic diagram of Pluronic nanoparticle with dense co-integration of CPPO and antracence dye (BDSA) as a ROS-activated CL nanoprobe. b-d) In vivo CL images of murine disease models of acute inflammation (a), rheumatic arthritis (b), and cancer (c) after systemic administration of CL nanoprobe. (Reprinted with permission from [36], ©2015, American Chemical Society)
Fig. 6
Fig. 6 a) Normalized absorption spectra of A431 cells labeled with the spherical AuNPs with or without the targeting ligand (left) and US and PA images of tumor-mimicking ex vivo mouse tissue (right) under laser illumination (right). (Reprinted with permission from [40], ©2009 American Chemical Society) b-c) TEM image (b, left) and optical absorption efficiency (b, right) of the rod-shaped AuNPs and US and PA image (c) of the AuNP-implanted mouse hind limb. Arrows show the locations of implanted gelled nanorod solution. (Reprinted with permission from [42], with permission from AIP Publishing)
Fig. 7
Fig. 7 US and PA images (a) and time dependent-PA signals (b) of SWCNT-injected mice. The images show the plane of one vertical slice (white dotted line) through the tumor. The US show the skin and tumor boundaries. (Reprinted by permission from Macmillan Publishers Ltd, Nature Nanotechnology [45], ©2008)
Fig. 8
Fig. 8 a) Schematic diagram of radioluminescent 198Au-incorporated NCs and Cerenkov luminescence images of EMT-6 tumor-bearing mice at 2 and 24 h post-injection after tail vain injection of the PEGylated 198Au-doped AuNCs. (Reprinted with permission from [51], ©2013, American Chemical Scoiety) b) Co-registered in vivo luminescence and X-ray images of the tumor-bearing mice at 24 h post-injection of the different types of 198Au-doped nanostructures. (Reprinted with permission from [52], ©2014, American Chemical Society)
Fig. 9
Fig. 9 a) Representative whole-body coronal PET (upper) and luminescence (bottom) images of U87MG tumor-bearing mice at the predetermined time points after intravenous injection of 64Cu-doped Q-dot 580. White and black arrows indicate the locations of tumor and liver, respectively. (Reprinted with permission from [53], ©2014, American Chemical Society) b) CRET images of U87MG tumor-bearing mice at 6 h post-injection of 64CuCl2, GSH-[64Cu]CIS/ZnS, and PEGylated GSH-[64Cu]CIS/ZnS Q-dots, respectively. Circles indicate the location of tumor area. (Reprinted with permission from [54], ©2015, American Chemical Society)
Fig. 10
Fig. 10 Utilization of NIR dye as a dual-modality (FL/PA) probe. (Reprinted with permission from [65], ©2014, American Chemical Society)
Fig. 11
Fig. 11 Procedure of pre- and intra-operative identification of sentinel lymph node using ICG-99mTc-Nanocolloid. (Reprinted from [89], ©2011, with permission from Elsevier)

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