Abstract
In-vivo multicolor photoacoustic (PA) flow cytometry for ultrasensitive molecular detection of the CD44+ circulating tumor cells (CTCs) is demonstrated on a mouse model of human breast cancer. Targeting of CTCs with stem-like phenotype, which are naturally shed from parent tumors, was performed with functionalized gold and magnetic nanoparticles. Results in vivo were verified in vitro with a multifunctional microscope, which integrates PA, photothermal (PT), fluorescent and transmission modules. Magnet-induced clustering of magnetic nanoparticles in individual cells significantly amplified PT and PA signals. The novel noninvasive platform, which integrates multispectral PA detection and PT therapy with a potential for multiplex targeting of many cancer biomarkers using multicolor nanoparticles, may prospectively solve grand challenges in cancer research for diagnosis and purging of undetectable yet tumor-initiating cells in circulation before they form metastasis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Ablation Techniques
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Acoustics*
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Animals
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Antibodies / immunology
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Antibodies / metabolism
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Blood Circulation*
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Breast Neoplasms / genetics
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Breast Neoplasms / pathology
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Breast Neoplasms / physiopathology
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Breast Neoplasms / therapy
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Carrier Proteins / metabolism
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Cell Death
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Flow Cytometry / methods*
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Folate Receptors, GPI-Anchored
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Folic Acid / metabolism
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Gene Expression Regulation, Neoplastic
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Gold / chemistry
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Gold / metabolism
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Humans
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Hyaluronan Receptors / immunology
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Hyaluronan Receptors / metabolism
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Light*
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Magnetics
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Metal Nanoparticles / chemistry
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Mice
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Nanotechnology*
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology*
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Phototherapy
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Receptors, Cell Surface / metabolism
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Temperature*
Substances
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Antibodies
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Carrier Proteins
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Folate Receptors, GPI-Anchored
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Hyaluronan Receptors
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Receptors, Cell Surface
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Gold
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Folic Acid