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.
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References
Weissleder R, Pittet MJ (2008) Imaging in the era of molecular oncology. Nature 452(7187):580–589
Willmann JK, van Bruggen N, Dinkelborg LM, Gambhir SS (2008) Molecular imaging in drug development. Nat Rev Drug Discov 7(7):591–607
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
Weissleder R (2001) A clearer vision for in vivo imaging. Nat Biotechnol 19(4):316–317
Dzurinko VL, Gurwood AS, Price JR (2004) Intravenous and indocyanine green angiography. Optometry 75(12):743–755
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
Sakka SG (2007) Assessing liver function. Curr Opin Crit Care 13(2):207–214
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
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
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
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
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
Ballou B, Ernst LA, Waggoner AS (2005) Fluorescence imaging of tumors in vivo. Curr Med Chem 12(7):795–805
Mujumdar RB, Ernst LA, Mujumdar SR, Lewis CJ, Waggoner AS (1993) Cyanine dye labeling reagents: sulfoindocyanine succinimidyl esters. Bioconjug Chem 4(2):105–111
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
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
Licha K (2002) Contrast agents for optical imaging. Top Curr Chem 222:1–29
Derfus AM, Chan CWC, Bhatia SN (2004) Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 4(1):11–18
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
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
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
Gupta B, Revagadea N, Hilbornb J (2007) Poly(lactic acid) fiber: an overview. Prog Polym Sci 32(4):455–482
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
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
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.
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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
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DOI: https://doi.org/10.1007/s10895-011-1007-z