TY - GEN
T1 - Photothermolysis by laser-induced microbubbles generated around gold nanorod clusters selectively formed in leukemia cells
AU - Lapotko, Dmitri
AU - Lukianova-Hleb, Ekaterina
AU - Zhdanok, Sergei
AU - Rostro, Betty
AU - Simonette, Rebecca
AU - Hafner, Jason
AU - Konopleva, Marina
AU - Andreeff, Michael
AU - Conjusteau, Andre
AU - Oraevsky, Alexander
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2008
Y1 - 2008
N2 - In an effort of developing clinical LANTCET (laser-activated nano-thermolysis as cell elimination technology) we achieved selective destruction of individual tumor cells through laser generation of vapor microbubbles around clusters of light absorbing gold nanorods (GNR) selectively formed in target tumor cells. Among all gold nanoparticles, nanorods offer the highest optical absorption in the near-infrared. We applied covalent conjugates of gold nanorods with targeting vectors such as monoclonal antibodies CD33 (specific for Acute Myeloid Leukemia), while GNR conjugates with polyethylene-glycol (PEG) were used as nonspecific targeting control. GNR clusters were formed inside the tumor cells at 37°C due to endocytosis of large concentration of nanorods accumulated on the surface of tumor cells targeted at 4°C. Formation of GNR clusters significantly reduces the threshold of tumor cell damage making LANTCET safe for normal cells. Appearance of GNR clusters was verified directly with optical resonance scattering microscopy. LANTCET was performed in vitro with living cells of (1) model myeloid K562 cells (CD33 positive), (2) primary human bone marrow CD33-positive blast cells from patients diagnosed with acute myeloid leukemia. Laser-induced microbubbles were generated and detected with a photothermal microscope equipped with a tunable Ti-Sa pulsed laser. GNT cluster formation caused a 100-fold decrease in the threshold optical fluence for laser microbubble generation in tumor cells compared with that in normal cells under the same targeting and irradiation conditions. Combining imaging based on resonance optical scattering with photothermal imaging of microbubbles, we developed a method for detection, image-guided treatment and monitoring of LANTCET. Pilot experiments were performed in flow mode bringing LANTCET closer to reality of clinical procedure of purging tumor cells from bone marrow grafts.
AB - In an effort of developing clinical LANTCET (laser-activated nano-thermolysis as cell elimination technology) we achieved selective destruction of individual tumor cells through laser generation of vapor microbubbles around clusters of light absorbing gold nanorods (GNR) selectively formed in target tumor cells. Among all gold nanoparticles, nanorods offer the highest optical absorption in the near-infrared. We applied covalent conjugates of gold nanorods with targeting vectors such as monoclonal antibodies CD33 (specific for Acute Myeloid Leukemia), while GNR conjugates with polyethylene-glycol (PEG) were used as nonspecific targeting control. GNR clusters were formed inside the tumor cells at 37°C due to endocytosis of large concentration of nanorods accumulated on the surface of tumor cells targeted at 4°C. Formation of GNR clusters significantly reduces the threshold of tumor cell damage making LANTCET safe for normal cells. Appearance of GNR clusters was verified directly with optical resonance scattering microscopy. LANTCET was performed in vitro with living cells of (1) model myeloid K562 cells (CD33 positive), (2) primary human bone marrow CD33-positive blast cells from patients diagnosed with acute myeloid leukemia. Laser-induced microbubbles were generated and detected with a photothermal microscope equipped with a tunable Ti-Sa pulsed laser. GNT cluster formation caused a 100-fold decrease in the threshold optical fluence for laser microbubble generation in tumor cells compared with that in normal cells under the same targeting and irradiation conditions. Combining imaging based on resonance optical scattering with photothermal imaging of microbubbles, we developed a method for detection, image-guided treatment and monitoring of LANTCET. Pilot experiments were performed in flow mode bringing LANTCET closer to reality of clinical procedure of purging tumor cells from bone marrow grafts.
KW - Cell damage
KW - Gold nanoparticle cluster
KW - Laser-induced bubble
KW - Purging
KW - Tumor cell
UR - http://www.scopus.com/inward/record.url?scp=42149086536&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42149086536&partnerID=8YFLogxK
U2 - 10.1117/12.771660
DO - 10.1117/12.771660
M3 - Conference contribution
AN - SCOPUS:42149086536
SN - 9780819470317
T3 - Progress in Biomedical Optics and Imaging - Proceedings of SPIE
BT - Photons Plus Ultrasound
T2 - 9th Conference on Photons Plus Ultrasound: Imaging and Sensing 2008
Y2 - 20 January 2008 through 23 January 2008
ER -