Skip to main content
Log in

Development of Novel Nanocarrier-Based Near-Infrared Optical Probes for In Vivo Tumor Imaging

  • Original Paper
  • Published:
Journal of Fluorescence Aims and scope Submit manuscript

Abstract

Optical imaging with near-infrared (NIR) fluorescent probes is a useful diagnostic technology for in vivo tumor detection. Our plan was to develop novel NIR fluorophore-micelle complex probes. IC7-1 and IC7-2 were synthesized as novel lipophilic NIR fluorophores, which were encapsulated in an amphiphilic polydepsipeptide micelle “lactosome”. The fluorophore-micelle complexes IC7-1 lactosome and IC7-2 lactosome were evaluated as NIR fluorescent probes for in vivo tumor imaging. IC7-1 and IC7-2 were synthesized and then encapsulated in lactosomes. The optical properties of IC7-1, IC7-2, IC7-1 lactosome and IC7-2 lactosome were measured. IC7-1 lactosome and IC7-2 lactosome were administered to tumor-bearing mice, and fluorescence images were acquired for 48 h. IC7-1 and IC7-2 were successfully synthesized in 12% and 6.3% overall yield, and maximum emission wavelengths in chloroform were observed at 858 nm and 897 nm, respectively. Aqueous buffered solutions of IC7-1 lactosome and IC7-2 lactosome showed similar fluorescence spectra in chloroform and higher or comparable quantum yields and higher photostability compared with ICG. Both lactosome probes specifically visualized tumor tissue 6 h post-administration. IC7-1 lactosome and IC7-2 lactosome could be promising NIR probes for in vivo tumor imaging.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

References

  1. Weissleder R, Pittet MJ (2008) Imaging in the era of molecular oncology. Nature 452(7187):580–589

    Article  PubMed  CAS  Google Scholar 

  2. Willmann JK, van Bruggen N, Dinkelborg LM, Gambhir SS (2008) Molecular imaging in drug development. Nat Rev Drug Discov 7(7):591–607

    Article  PubMed  CAS  Google Scholar 

  3. Ntziachristos V, Ripoll J, Wang LV, Weissleder R (2005) Looking and listening to light: the evolution of whole-body photonic imaging. Nat Biotechnol 23(3):313–320

    Article  PubMed  CAS  Google Scholar 

  4. Weissleder R (2001) A clearer vision for in vivo imaging. Nat Biotechnol 19(4):316–317

    Article  PubMed  CAS  Google Scholar 

  5. Dzurinko VL, Gurwood AS, Price JR (2004) Intravenous and indocyanine green angiography. Optometry 75(12):743–755

    Article  PubMed  Google Scholar 

  6. Landsman ML, Kwant G, Mook GA, Zijlstra WG (1976) Light-absorbing properties, stability, and spectral stabilization of indocyanine green. J Appl Physiol 40(4):575–583

    PubMed  CAS  Google Scholar 

  7. Sakka SG (2007) Assessing liver function. Curr Opin Crit Care 13(2):207–214

    Article  PubMed  Google Scholar 

  8. Makino A, Kizaka-Kondoh S, Yamahara R, Hara I, Kanzaki T, Ozeki E, Hiraoka M, Kimura S (2009) Near-infrared fluorescence tumor imaging using nanocarrier composed of poly(L-lactic acid)-block-poly(sarcosine) amphiphilic polydepsipeptide. Biomaterials 30(28):5156–5160

    Article  PubMed  CAS  Google Scholar 

  9. Makino A, Yamahara R, Ozeki E, Kimura S (2007) Preparation of novel polymer assemblies, “lactosome”, composed of Poly(L-lactic acid) and poly(sarcosine). Chem Lett 36(10):1220–1221

    Article  CAS  Google Scholar 

  10. Lee H, Mason JC, Achilefu S (2006) Heptamethine cyanine dyes with a robust C–C bond at the central position of the chromophore. J Org Chem 71(20):7862–7865

    Article  PubMed  CAS  Google Scholar 

  11. Strekowski L, Lipowska M, Patonay G (1992) Substitution reactions of a nucleofugal group in heptamethine cyanine dyes. Synthesis of an isothiocyanato derivative for labeling of proteins with a near-infrared chromophore. J Org Chem 57(17):4578–4580

    Article  CAS  Google Scholar 

  12. Constantin TP, Silva GL, Robertson KL, Hamilton TP, Fague K, Waggoner AS, Armitage BA (2008) Synthesis of new fluorogenic cyanine dyes and incorporation into RNA fluoromodules. Org Lett 10(8):1561–1564

    Article  PubMed  CAS  Google Scholar 

  13. Ballou B, Ernst LA, Waggoner AS (2005) Fluorescence imaging of tumors in vivo. Curr Med Chem 12(7):795–805

    Article  PubMed  CAS  Google Scholar 

  14. Mujumdar RB, Ernst LA, Mujumdar SR, Lewis CJ, Waggoner AS (1993) Cyanine dye labeling reagents: sulfoindocyanine succinimidyl esters. Bioconjug Chem 4(2):105–111

    Article  PubMed  CAS  Google Scholar 

  15. Kobayashi H, Koyama Y, Barrett T, Hama Y, Regino CA, Shin IS, Jang BS, Le N, Paik CH, Choyke PL, Urano Y (2007) Multimodal nanoprobes for radionuclide and five-color near-infrared optical lymphatic imaging. ACS Nano 1(4):258–264

    Article  PubMed  CAS  Google Scholar 

  16. Koyama Y, Barrett T, Hama Y, Ravizzini G, Choyke PL, Kobayashi H (2007) In vivo molecular imaging to diagnose and subtype tumors through receptor-targeted optically labeled monoclonal antibodies. Neoplasia 9(12):1021–1029

    Article  PubMed  CAS  Google Scholar 

  17. Licha K (2002) Contrast agents for optical imaging. Top Curr Chem 222:1–29

    Article  CAS  Google Scholar 

  18. Derfus AM, Chan CWC, Bhatia SN (2004) Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 4(1):11–18

    Article  CAS  Google Scholar 

  19. Kirchner C, Liedl T, Kudera S, Pellegrino T, Munoz Javier A, Gaub HE, Stolzle S, Fertig N, Parak WJ (2005) Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett 5(2):331–338

    Article  PubMed  CAS  Google Scholar 

  20. Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46(12 Pt 1):6387–6392

    PubMed  CAS  Google Scholar 

  21. Senior JH (1987) Fate and behavior of liposomes in vivo: a review of controlling factors. Crit Rev Ther Drug Carrier Systems 3(2):123–193

    CAS  Google Scholar 

  22. Gupta B, Revagadea N, Hilbornb J (2007) Poly(lactic acid) fiber: an overview. Prog Polym Sci 32(4):455–482

    Article  CAS  Google Scholar 

  23. Tsai G, Lane HY, Yang P, Chong MY, Lange N (2004) Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry 55(5):452–456

    Article  PubMed  CAS  Google Scholar 

  24. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65(1–2):271–284

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

This study was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. Part of this study was supported by the New Energy and Industrial Technology Development Organization (NEDO), Japan. We thank Dojindo Laboratories (Kumamoto, Japan) for supporting the syntheses of IC7-1 and IC7-2.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hideo Saji.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shimizu, Y., Temma, T., Hara, I. et al. Development of Novel Nanocarrier-Based Near-Infrared Optical Probes for In Vivo Tumor Imaging. J Fluoresc 22, 719–727 (2012). https://doi.org/10.1007/s10895-011-1007-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10895-011-1007-z

Keywords

Navigation