Photothermolysis by laser-induced microbubbles generated around gold nanorod clusters selectively formed in leukemia cells

Dmitri Lapotko; Ekaterina Lukianova-Hleb; Sergei Zhdanok; Betty Rostro; Rebecca Simonette; Jason Hafner; Marina Konopleva; Michael Andreeff; Andre Conjusteau; Alexander Oraevsky

doi:10.1117/12.771660

28 February 2008 Photothermolysis by laser-induced microbubbles generated around gold nanorod clusters selectively formed in leukemia cells

Dmitri Lapotko, Ekaterina Lukianova-Hleb, Sergei Zhdanok, Betty Rostro, Rebecca Simonette, Jason Hafner, Marina Konopleva, Michael Andreeff, Andre Conjusteau, Alexander Oraevsky

Author Affiliations +

Proceedings Volume 6856, Photons Plus Ultrasound: Imaging and Sensing 2008: The Ninth Conference on Biomedical Thermoacoustics, Optoacoustics, and Acousto-optics; 68560K (2008) https://doi.org/10.1117/12.771660
Event: SPIE BiOS, 2008, San Jose, California, United States

Abstract

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.

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Dmitri Lapotko, Ekaterina Lukianova-Hleb, Sergei Zhdanok, Betty Rostro, Rebecca Simonette, Jason Hafner, Marina Konopleva, Michael Andreeff, Andre Conjusteau, and Alexander Oraevsky "Photothermolysis by laser-induced microbubbles generated around gold nanorod clusters selectively formed in leukemia cells", Proc. SPIE 6856, Photons Plus Ultrasound: Imaging and Sensing 2008: The Ninth Conference on Biomedical Thermoacoustics, Optoacoustics, and Acousto-optics, 68560K (28 February 2008); https://doi.org/10.1117/12.771660

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