Near-infrared emitting fluorophore-doped calcium phosphate nanoparticles for in vivo imaging of human breast cancer

Erhan I. Altinoǧlu, Timothy J. Russin, James M. Kaiser, Brian M. Barth, Peter C. Eklund, Mark Kester, James Hansell Adair

Research output: Contribution to journalArticle

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Abstract

Early detection is a crucial element for the timely diagnosis and successful treatment of all human cancers but is limited by the sensitivity of current imaging methodologies. We have synthesized and studied bioresorbable calcium phosphate nanoparticles (CPNPs) in which molecules of the near-infrared (NIR) emitting fluorophore, indocyanine green (ICG), are embedded. The ICG-CPNPs demonstrate exceptional colloidal and optical characteristics. Suspensions consisting of 16 nm average diameter particles are colloidally stable in physiological solutions (phosphate buffered 0.15 M saline (PBS), pH 7.4) with carboxylate or polyethylene glycol (PEG) surface functionality. ICG-doped CPNPs exhibit significantly greater intensity at the maximum emission wavelength relative to the free constituent fluorophore, consistent with the multiple molecules encapsulated per particle. The quantum efficiency per molecule of the ICG-CPNPs is 200% greater at 0.049 ± 0.003 over the free fluorophore in PBS. Photostability based on fluorescence half-life of encapsulated ICG in PBS is 500% longer under typical clinical imaging conditions relative to the free dye. PEGylated ICG-CPNPs accumulate in solid, 5 mm diameter xenograft breast adenocarcinoma tumors via enhanced retention and permeability (EPR) within 24 h after systemic tail vein injection in a nude mouse model. Ex situ tissue imaging further verifies the facility of the ICG-CPNPs for deep-tissue imaging with NIR signals detectable from depths up to 3 cm in porcine muscle tissue. Our ex vivo and in vivo experiments verify the promise of the NIR CPNPs for diagnostic imaging in the early detection of solid tumors.

Original languageEnglish (US)
Pages (from-to)2075-2084
Number of pages10
JournalACS Nano
Volume2
Issue number10
DOIs
StatePublished - Oct 1 2008

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Indocyanine Green
calcium phosphates
Fluorophores
Calcium phosphate
breast
cancer
Nanoparticles
Infrared radiation
Imaging techniques
nanoparticles
phosphates
Phosphates
Tissue
Molecules
Tumors
tumors
molecules
Medical imaging
muscles
calcium phosphate

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Altinoǧlu, E. I., Russin, T. J., Kaiser, J. M., Barth, B. M., Eklund, P. C., Kester, M., & Adair, J. H. (2008). Near-infrared emitting fluorophore-doped calcium phosphate nanoparticles for in vivo imaging of human breast cancer. ACS Nano, 2(10), 2075-2084. https://doi.org/10.1021/nn800448r
Altinoǧlu, Erhan I. ; Russin, Timothy J. ; Kaiser, James M. ; Barth, Brian M. ; Eklund, Peter C. ; Kester, Mark ; Adair, James Hansell. / Near-infrared emitting fluorophore-doped calcium phosphate nanoparticles for in vivo imaging of human breast cancer. In: ACS Nano. 2008 ; Vol. 2, No. 10. pp. 2075-2084.
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Altinoǧlu, EI, Russin, TJ, Kaiser, JM, Barth, BM, Eklund, PC, Kester, M & Adair, JH 2008, 'Near-infrared emitting fluorophore-doped calcium phosphate nanoparticles for in vivo imaging of human breast cancer', ACS Nano, vol. 2, no. 10, pp. 2075-2084. https://doi.org/10.1021/nn800448r

Near-infrared emitting fluorophore-doped calcium phosphate nanoparticles for in vivo imaging of human breast cancer. / Altinoǧlu, Erhan I.; Russin, Timothy J.; Kaiser, James M.; Barth, Brian M.; Eklund, Peter C.; Kester, Mark; Adair, James Hansell.

In: ACS Nano, Vol. 2, No. 10, 01.10.2008, p. 2075-2084.

Research output: Contribution to journalArticle

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Altinoǧlu EI, Russin TJ, Kaiser JM, Barth BM, Eklund PC, Kester M et al. Near-infrared emitting fluorophore-doped calcium phosphate nanoparticles for in vivo imaging of human breast cancer. ACS Nano. 2008 Oct 1;2(10):2075-2084. https://doi.org/10.1021/nn800448r