Skip to main content

Advertisement

Log in

Infrared fluorescence imaging of infarcted hearts with Ag2S nanodots

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Ag2S nanodots have already been demonstrated as promising near-infrared (NIR-II, 1.0–1.45 μm) emitting nanoprobes with low toxicity, high penetration and high resolution for in vivo imaging of, for example, tumors and vasculature. In this work, we have systematically investigated the potential application of functionalized Ag2S nanodots for accurate imaging of damaged myocardium tissues after a myocardial infarction induced by either partial or global ischemia. Ag2S nanodots surface-functionalized with the angiotensin II peptide (ATII) have shown over 10-fold enhanced binding efficiency to damaged tissues than non-specifically (PEG) functionalized Ag2S nanodots due to their interaction with the upregulated angiotensin II receptor type I (AT1R). It is demonstrated how the NIR-II images generated by ATII-functionalized Ag2S nanodots contain valuable information about the location and extension of damaged tissue in the myocardium allowing for a proper identification of the occluded artery as well as an indirect evaluation of the damage level. The potential application of Ag2S nanodots in the near future for in vivo imaging of myocardial infarction was also corroborated by performing proof of concept whole body imaging experiments.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. WHO; World Heart Federation; World Stroke Organization. Global Atlas on Cardiovascular Disease Prevention and Control; World Health Organization in Collaboration with the World Heart Federation and the World Stroke Organization: Geneva, 2011; pp 155

    Google Scholar 

  2. Luengo-Fernández, R.; Leal, J.; Gray, A.; Petersen, S.; Rayner, M. Cost of cardiovascular diseases in the United Kingdom. Heart 2006, 92, 1384–1389.

    Article  Google Scholar 

  3. Mahmoudi, M.; Yu, M.; Serpooshan, V.; Wu, J. C.; Langer, R.; Lee, R. T.; Karp, J. M.; Farokhzad, O. C. Multiscale technologies for treatment of ischemic cardiomyopathy. Nat. Nanotechnol. 2017, 12, 845–855.

    Article  Google Scholar 

  4. Ximendes, E. C.; Rocha, U.; del Rosal, B.; Vaquero, A.; Sanz-Rodríguez, F.; Monge, L.; Ren, F. Q.; Vetrone, F.; Ma, D. L.; García-Solé, J. et al. In vivo ischemia detection by luminescent nanothermometers. Adv. Health. Mater. 2017, 6, 1601195.

    Article  Google Scholar 

  5. Ruvinov, E.; Dvir, T.; Leor, J.; Cohen, S. Myocardial repair: From salvage to tissue reconstruction. Expert Rev. Cardiovasc. Ther. 2008, 6, 669–686.

    Article  Google Scholar 

  6. Flachskampf, F. A.; Schmid, M.; Rost, C.; Achenbach, S.; DeMaria, A. N.; Daniel, W. G. Cardiac imaging after myocardial infarction. Eur. Heart J. 2011, 32, 272–283.

    Article  Google Scholar 

  7. Mulder, W. J.; Griffioen, A. W.; Strijkers, G. J.; Cormode, D. P.; Nicolay, K.; Fayad, Z. A. Magnetic and fluorescent nanoparticles for multimodality imaging. Nanomedicine 2007, 2, 307–324.

    Article  Google Scholar 

  8. Lozano, O.; Torres-Quintanilla, A.; García-Rivas, G. Nanomedicine for the cardiac myocyte: Where are we? J. Control. Release 2018, 271, 149–165.

    Article  Google Scholar 

  9. Hu, J.; Ortgies, D. H.; Martín Rodríguez, E.; Rivero, F.; Aguilar Torres, R.; Alfonso, F.; Fernández, N.; Carreño-Tarragona, G.; Monge, L.; Sanz-Rodriguez, F. et al. Optical nanoparticles for cardiovascular imaging. Adv. Opt. Mater. 2018, 6, 1800626.

    Article  Google Scholar 

  10. Dvir, T.; Bauer, M.; Schroeder, A.; Tsui, J. H.; Anderson, D. G.; Langer, R.; Liao, R.; Kohane, D. S. Nanoparticles targeting the infarcted heart. Nano Lett. 2011, 11, 4411–4414.

    Article  Google Scholar 

  11. Jiang, W. S.; Rutherford, D.; Vuong, T.; Liu, H. N. Nanomaterials for treating cardiovascular diseases: A review. Bioact. Mater. 2017, 2, 185–198.

    Article  Google Scholar 

  12. Stendahl, J. C.; Sinusas, A. J. Nanoparticles for cardiovascular imaging and therapeutic delivery, Part 1: Compositions and features. J. Nucl. Med. 2015, 56, 1469–1475.

    Article  Google Scholar 

  13. Sharma, R.; Kwon, S. New applications of nanoparticles in cardiovascular imaging. J. Exp. Nanosci. 2007, 2, 115–126.

    Article  Google Scholar 

  14. Taillefer, R.; Tamaki, N. New Radiotracers in Cardiac Imaging: Principles and Applications; Appleton & Lange: Stamford, Connecticut, 1999.

    Google Scholar 

  15. Sosnovik, D. E.; Schellenberger, E. A.; Nahrendorf, M.; Novikov, M. S.; Matsui, T.; Dai, G.; Reynolds, F.; Grazette, L.; Rosenzweig, A.; Weissleder, R. et al. Magnetic resonance imaging of cardiomyocyte apoptosis with a novel magneto-optical nanoparticle. Magn. Reson. Med. 2005, 54, 718–724.

    Article  Google Scholar 

  16. Ruan, S. B.; Wan, J. Y.; Fu, Y.; Han, K.; Li, X.; Chen, J. T.; Zhang, Q. Y.; Shen, S.; He, Q.; Gao, H. L. PEGylated fluorescent carbon nanoparticles for noninvasive heart imaging. Bioconjug. Chem. 2014, 25, 1061–1068.

    Article  Google Scholar 

  17. Lundy, D. J.; Chen, K. H.; Toh, E. K. W.; Hsieh, P. C. H. Distribution of systemically administered nanoparticles reveals a size-dependent effect immediately following cardiac ischaemia-reperfusion injury. Sci. Rep. 2016, 6, 25613.

    Article  Google Scholar 

  18. Lipinski, M. J.; Albelda, M. T.; Frias, J. C.; Anderson, S. A.; Luger, D.; Westman, P. C.; Escarcega, R. O.; Hellinga, D. G.; Waksman, R.; Arai, A. E. et al. Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium. Cardiovasc. Revasc. Med. 2016, 17, 106–112.

    Article  Google Scholar 

  19. Sosnovik, D. E.; Nahrendorf, M.; Deliolanis, N.; Novikov, M.; Aikawa, E.; Josephson, L.; Rosenzweig, A.; Weissleder, R.; Ntziachristos, V. Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo. Circulation 2007, 115, 1384–1391.

    Article  Google Scholar 

  20. Nahrendorf, M.; Sosnovik, D. E.; Waterman, P.; Swirski, F. K.; Pande, A. N.; Aikawa, E.; Figueiredo, J. L.; Pittet, M. J.; Weissleder, R. Dual channel optical tomographic imaging of leukocyte recruitment and protease activity in the healing myocardial infarct. Circ. Res. 2007, 100, 1218–1225.

    Article  Google Scholar 

  21. Ferreira, M. P. A.; Ranjan, S.; Kinnunen, S.; Correia, A.; Talman, V.; Mäkilä, E.; Barrios-Lopez, B.; Kemell, M.; Balasubramanian, V.; Salonen, J. et al. Drug-loaded multifunctional nanoparticles targeted to the endocardial layer of the injured heart modulate hypertrophic signaling. Small 2017, 13, 1701276.

    Article  Google Scholar 

  22. Sosnovik, D. E.; Garanger, E.; Aikawa, E.; Nahrendorf, M.; Figuiredo, J. L.; Dai, G. P.; Reynolds, F.; Rosenzweig, A.; Weissleder, R.; Josephson, L. Molecular MRI of cardiomyocyte apoptosis with simultaneous delayedenhancement MRI distinguishes apoptotic and necrotic myocytes in vivo: Potential for midmyocardial salvage in acute ischemia. Circ. Cardiovasc. Imaging 2009, 2, 460–467.

    Article  Google Scholar 

  23. Bashkatov, A. N.; Genina, E. A.; Tuchin, V. V. Optical properties of skin, subcutaneous, and muscle tissues: A review. J. Innov. Opt. Health Sci. 2011, 4, 9–38.

    Article  Google Scholar 

  24. Smith, A. M.; Mancini, M. C.; Nie, S. M. Second window for in vivo imaging. Nat. Nanotechnol. 2009, 4, 710–711.

    Article  Google Scholar 

  25. Jaque, D.; Richard, C.; Viana, B.; Soga, K.; Liu, X. G.; García Solé, J. Inorganic nanoparticles for optical bioimaging. Adv. Opt. Photonics 2016, 8, 1–103.

    Article  Google Scholar 

  26. Welsher, K.; Sherlock, S. P.; Dai, H. J. Deep-tissue anatomical imaging of mice using carbon nanotube fluorophores in the second near-infrared window. Proc. Natl. Acad. Sci. USA 2011, 108, 8943–8948.

    Article  Google Scholar 

  27. Villa, I.; Vedda, A.; Cantarelli, I. X.; Pedroni, M.; Piccinelli, F.; Bettinelli, M.; Speghini, A.; Quintanilla, M.; Vetrone, F.; Rocha, U. et al. 1.3 μm emitting SrF2:Nd3+ nanoparticles for high contrast in vivo imaging in the second biological window. Nano Res. 2015, 8, 649–665.

    Article  Google Scholar 

  28. del Rosal, B.; Villa, I.; Jaque, D.; Sanz-Rodríguez, F. In vivo autofluorescence in the biological windows: The role of pigmentation. J. Biophotonics 2016, 9, 1059–1067.

    Article  Google Scholar 

  29. Zhang, Y. J.; Liu, Y. S.; Li, C. Y.; Chen, X. Y.; Wang, Q. B. Controlled synthesis of Ag2S quantum dots and experimental determination of the exciton Bohr radius. J. Phys. Chem. C 2014, 118, 4918–4923.

    Article  Google Scholar 

  30. Sadovnikov, S. I.; Gusev, A. I. Recent progress in nanostructured silver sulfide: From synthesis and nonstoichiometry to properties. J. Mater. Chem. A 2017, 5, 17676–17704.

    Article  Google Scholar 

  31. Hu, F.; Li, C. Y.; Zhang, Y. J.; Wang, M.; Wu, D. M.; Wang, Q. B. Real-time in vivo visualization of tumor therapy by a near-infrared-II Ag2S quantum dot-based theranostic nanoplatform. Nano Res. 2015, 8, 1637–1647.

    Article  Google Scholar 

  32. Kubie, L.; King, L. A.; Kern, M. E.; Murphy, J. R.; Kattel, S.; Yang, Q.; Stecher, J. T.; Rice, W. D.; Parkinson, B. A. Synthesis and characterization of ultrathin silver sulfide nanoplatelets. ACS Nano 2017, 11, 8471–8477.

    Article  Google Scholar 

  33. Li, C. Y.; Li, F.; Zhang, Y. J.; Zhang, W. J.; Zhang, X. E.; Wang, Q. B. Real-time monitoring surface chemistry-dependent in vivo behaviors of protein nanocages via encapsulating an NIR-II Ag2S quantum dot. ACS Nano 2015, 9, 12255–12263.

    Article  Google Scholar 

  34. Zhang, Y.; Hong, G. S.; Zhang, Y. J.; Chen, G. C.; Li, F.; Dai, H. J.; Wang, Q. B. Ag2S Quantum dot: A bright and biocompatible fluorescent nanoprobe in the second near-infrared window. ACS Nano 2012, 6, 3695–3702.

    Article  Google Scholar 

  35. Hong, G. S.; Robinson, J. T.; Zhang, Y. J.; Diao, S.; Antaris, A. L.; Wang, Q. B.; Dai, H. J. In vivo fluorescence imaging with Ag2S quantum dots in the second near-infrared region. Angew. Chem., Int. Ed. 2012, 51, 9818–9821.

    Article  Google Scholar 

  36. Wu, C. X.; Zhang, Y. J.; Li, Z.; Li, C. Y.; Wang, Q. B. A novel photoacoustic nanoprobe of ICG@PEG-Ag2S for atherosclerosis targeting and imaging in vivo. Nanoscale 2016, 8, 12531–12539.

    Article  Google Scholar 

  37. Zhang, Y.; Zhang, Y. J.; Hong, G. S.; He, W.; Zhou, K.; Yang, K.; Li, F.; Chen, G. C.; Liu, Z.; Dai, H. J. et al. Biodistribution, pharmacokinetics and toxicology of Ag2S near-infrared quantum dots in mice. Biomaterials 2013, 34, 3639–3646.

    Article  Google Scholar 

  38. Li, C. Y.; Zhang, Y. J.; Wang, M.; Zhang, Y.; Chen, G. C.; Li, L.; Wu, D. M.; Wang, Q. B. In vivo real-time visualization of tissue blood flow and angiogenesis using Ag2S quantum dots in the NIR-II window. Biomaterials 2014, 35, 393–400.

    Article  Google Scholar 

  39. Santos, H. D. A.; Ruiz, D.; Lifante, G.; Jacinto, C.; Juarez, B. H.; Jaque, D. Time resolved spectroscopy of infrared emitting Ag2S nanocrystals for subcutaneous thermometry. Nanoscale 2017, 9, 2505–2513.

    Article  Google Scholar 

  40. Santos, H. D. A.; Ximendes, E. C.; del Carmen Iglesias-de la Cruz, M.; Chaves-Coira, I.; del Rosal, B.; Jacinto, C.; Monge, L.; Rubia-Rodríguez, I.; Ortega, D.; Mateos, S. et al. In vivo early tumor detection and diagnosis by infrared luminescence transient nanothermometry. Adv. Funct. Mater. 2018, 28, 1803924.

    Article  Google Scholar 

  41. Chang, P. J.; Cheng, H. Y.; Lin, W. W.; Li, X. R.; Zhao, F. Y. A stable and active AgxS crystal preparation and its performance as photocatalyst. Chin. J. Catal. 2015, 36, 564–571.

    Article  Google Scholar 

  42. Yang, T.; Tang, Y. A.; Liu, L.; Lv, X. Y.; Wang, Q. L.; Ke, H. T.; Deng, Y. B.; Yang, H.; Yang, X. L.; Liu, G. et al. Size-dependent Ag2S nanodots for second near-infrared fluorescence/photoacoustics imaging and simultaneous photothermal therapy. ACS Nano 2017, 11, 1848–1857.

    Article  Google Scholar 

  43. Hong, G. S.; Lee, J. C.; Jha, A.; Diao, S.; Nakayama, K. H.; Hou, L. Q.; Doyle, T. C.; Robinson, J. T.; Antaris, A. L.; Dai, H. J. et al. Near-infrared II fluorescence for imaging hindlimb vessel regeneration with dynamic tissue perfusion measurement. Circ. Cardiovasc. Imaging 2014, 7, 517–525.

    Article  Google Scholar 

  44. Hennig, R.; Pollinger, K.; Tessmar, J.; Goepferich, A. Multivalent targeting of AT1 receptors with angiotensin II-functionalized nanoparticles. J. Drug Target. 2015, 23, 681–689.

    Article  Google Scholar 

  45. Molavi, B.; Chen, J. W.; Mehta, J. L. Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK. Am. J. Physiol. Heart. Circ. Physiol. 2006, 291, H687–H693.

    Article  Google Scholar 

  46. Nio, Y.; Matsubara, H.; Murasawa, S.; Kanasaki, M.; Inada, M. Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction. J. Clin. Invest. 1995, 95, 46–54.

    Article  Google Scholar 

  47. Busche, S.; Gallinat, S.; Bohle, R. M.; Reinecke, A.; Seebeck, J.; Franke, F.; Fink, L.; Zhu, M. Y.; Sumners, C.; Unger, T. Expression of angiotensin AT1 and AT2 receptors in adult rat cardiomyocytes after myocardial infarction: A single-cell reverse transcriptase-polymerase chain reaction study. Am. J. Pathol. 2000, 157, 605–611.

    Article  Google Scholar 

  48. Bell, R. M.; Mocanu, M. M.; Yellon, D. M. Retrograde heart perfusion: The Langendorff technique of isolated heart perfusion. J. Mol. Cell. Cardiol. 2011, 50, 940–950.

    Article  Google Scholar 

  49. Ostadal, B.; Netuka, I.; Maly, J.; Besik, J.; Ostadalova, I. Gender differences in cardiac ischemic injury and protection—experimental aspects. Exp. Biol. Med. 2009, 234, 1011–1019.

    Article  Google Scholar 

  50. Jeong, S.; Jung, Y.; Bok, S.; Ryu, Y. M.; Lee, S.; Kim, Y. E.; Song, J.; Kim, M.; Kim, S. Y.; Ahn, G. O. et al. Multiplexed in vivo imaging using size-controlled quantum dots in the second near-infrared window. Adv. Health. Mater. 2018, 7, 1800695.

    Article  Google Scholar 

  51. Benayas, A.; Ren, F. Q.; Carrasco, E.; Marzal, V.; del Rosal, B.; Gonfa, B. A.; Juarranz, Á Sanz-Rodríguez, F.; Jaque, D.; García-Solé, J. et al. PbS/CdS/ZnS quantum dots: A multifunctional platform for in vivo nearinfrared low-dose fluorescence imaging. Adv. Funct. Mater. 2015, 25, 6650–6659.

    Article  Google Scholar 

  52. Robinson, J. T.; Hong, G. S.; Liang, Y. Y.; Zhang, B.; Yaghi, O. K.; Dai, H. J. In vivo fluorescence imaging in the second near-infrared window with long circulating carbon nanotubes capable of ultrahigh tumor uptake. J. Am. Chem. Soc. 2012, 134, 10664–10669.

    Article  Google Scholar 

  53. Bhavane, R.; Starosolski, Z.; Stupin, I.; Ghaghada, K. B.; Annapragada, A. NIR-II fluorescence imaging using indocyanine green nanoparticles. Sci. Rep. 2018, 8, 14455.

    Article  Google Scholar 

  54. Carr, J. A.; Franke, D.; Caram, J. R.; Perkinson, C. F.; Saif, M.; Askoxylakis, V.; Datta, M.; Fukumura, D.; Jain, R. K.; Bawendi, M. G. et al. Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green. Proc. Natl. Acad. Sci. USA 2018, 115, 4465–4470.

    Article  Google Scholar 

  55. Ortgies, D. H.; Tan, M. L.; Ximendes, E. C.; del Rosal, B.; Hu, J.; Xu, L.; Wang, X. D.; Martín Rodríguez, E.; Jacinto, C.; Fernandez, N. et al. Lifetime-encoded infrared-emitting nanoparticles for in vivo multiplexed imaging. ACS Nano 2018, 12, 4362–4368.

    Article  Google Scholar 

  56. Yang, B. C.; Li, D. Y.; Phillips, M. I.; Mehta, P.; Mehta, J. L. Myocardial angiotensin II receptor expression and ischemia-reperfusion injury. Vasc. Med. 1998, 3, 121–130.

    Article  Google Scholar 

  57. Anversa, P.; Leri, A.; Li, B. S.; Liu, Y.; Di Somma, S.; Kajstura, J. Ischemic cardiomyopathy and the cellular renin-angiotensin system. J. Heart Lung Transplant. 2000, 19, S1–S11.

    Article  Google Scholar 

  58. Sato, M.; Engelman, R. M.; Otani, H.; Maulik, N.; Rousou, J. A.; Flack III, J. E.; Deaton, D. W.; Das, D. K. Myocardial protection by preconditioning of heart with losartan, an angiotensin II type 1-receptor blocker: Implication of bradykinin-dependent and bradykinin-independent mechanisms. Circulation 2000, 102, III346–III351.

    Google Scholar 

  59. Greish, K. Enhanced permeability and retention (EPR) effect for anticancer nanomedicine drug targeting. In Cancer Nanotechnology: Methods and Protocols. Grobmyer, S. R.; Moudgil, B. M., Eds.; Humana Press: Totowa, N.J., 2010.

    Google Scholar 

  60. Wang, L. V.; Hu, S. Photoacoustic tomography: In vivo imaging from organelles to organs. Science 2012, 335, 1458–1462.

    Article  Google Scholar 

Download references

Acknowledgements

This work was partially supported by the Ministerio de Economía y Competitividad de España (MAT2016-75362-C3-1-R) and (MAT2017-83111R), by the Instituto de Salud Carlos III (PI16/ 00812), by the Comunidad Autónoma de Madrid (B2017/BMD-3867RENIMCM), and co-financed by the European Structural and investment fond. Additional funding was provided by the European Commission Horizon 2020 project NanoTBTech, the Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal project IMP18_38 (2018/0265), and also by COST action CM1403. D. H. O. is grateful to the Instituto de Salud Carlos III for a Sara Borrell scholarship (No. CD17/00210).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daniel Jaque.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ortgies, D.H., García-Villalón, Á.L., Granado, M. et al. Infrared fluorescence imaging of infarcted hearts with Ag2S nanodots. Nano Res. 12, 749–757 (2019). https://doi.org/10.1007/s12274-019-2280-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-019-2280-4

Keywords

Navigation