Nanotechnology-based molecular photoacoustic and photothermal flow cytometry platform for in-vivo detection and killing of circulating cancer stem cells.
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.
Galanzha
Ekaterina I
EI
Department of Biological and Agricultural Engineering and Institute for Nanoscale Materials Science and Engineering, University of Arkansas, Fayetteville, AR, 72701, USA. egalanzha@uams.edu
Kim
Jin-Woo
JW
Zharov
Vladimir P
VP
D055011:Ablation Techniques; D000162:Acoustics; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D001775:Blood Circulation; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D002352:Carrier Proteins / Q000378:metabolism; D016923:Cell Death; D005434:Flow Cytometry / Q000379:methods*; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006046:Gold / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism; D008027:Light; D008280:Magnetics; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D036103:Nanotechnology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010789:Phototherapy; D011956:Receptors, Cell Surface / Q000378:metabolism; D013696:Temperature
D000906:Antibodies; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; D006046:Gold; D005492:Folic Acid