25 April 2005 Laser activated nanothermolysis of leukemia cells monitored by photothermal microscopy
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We are developing new diagnostic and therapeutic technologies for leukemia based on selective targeting of leukemia cells with gold nanoparticles and thermomechanical destruction of the tumor cells with laser-induced microbubbles. Clusters of spherical gold nanoparticles that have strong optical absorption of laser pulses at 532 nm served as nucleation sites of vapor microbubbles. The nanoparticles were targeted selectively to leukemia cells using leukemia-specific surface receptors and a set of two monoclonal antibodies. Application of a primary myeloid-specific antibody to tumor cells followed by targeting the cells with 30-nm nanoparticles conjugated with a secondary antibody (IgG) resulted in formation of nanoparticulate clusters due to aggregation of IgGs. Formation of clusters resulted in substantial decrease of the damage threshold for target cells. The results encourage development of Laser Activated Nanothermolysis as a Cell Elimination Therapy (LANCET) for leukemia. The proposed technology can be applied separately or in combination with chemotherapy for killing leukemia cells without damage to other blood cells. Potential applications include initial reduction of concentration of leukemia cells in blood prior to chemotherapy and treatment of residual tumor cells after the chemotherapy. Laser-induced bubbles in individual cells and cell damage were monitored by analyzing profile of photothermal response signals over the entire cell after irradiation with a single 10-ns long laser pulse. Photothermal microscopy was utilized for imaging formation of microbubbles around nanoparticulate clusters.
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Dmitri Lapotko, Dmitri Lapotko, Ekaterina Lukianova, Ekaterina Lukianova, Alexander Shnip, Alexander Shnip, George Zheltov, George Zheltov, Michail Potapnev, Michail Potapnev, Valeriy Savitsky, Valeriy Savitsky, Olga Klimovich, Olga Klimovich, Alexander Oraevsky, Alexander Oraevsky, } "Laser activated nanothermolysis of leukemia cells monitored by photothermal microscopy", Proc. SPIE 5697, Photons Plus Ultrasound: Imaging and Sensing 2005: The Sixth Conference on Biomedical Thermoacoustics, Optoacoustics, and Acousto-optics, (25 April 2005); doi: 10.1117/12.596372; https://doi.org/10.1117/12.596372

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