Mikhail Berezin, PhD
Washington University School of Medicine
Department of Radiology
Campus Box 8225
510 S. Kingshighway Blvd., Barnard Bldg., Room 6604A
St. Louis, MO 63110
Dr. Berezin’s lab focuses on the development of novel optically active probes ranging from small molecules to nanoparticles, and the development of optical instrumentation for spectroscopy and imaging using knowledge of excited states. Our research interest lies in the investigation and application of molecular excited states and their reactions for medical imaging and clinical treatment. Excited states are the cornerstone of a variety of chemical, physical, and biological phenomena. The ability to probe, investigate, and control excited states is one of the largest achievements of modern science. Currently we are involved in the three projects described below:
Optically active nanothermometers for diagnostics and treatment
The thermal ablation of tumors is an alternative method to overcome the problems associated with open surgery and is founded upon the idea of destroying tumors through the direct application of heat to the tumor site. Thermal treatment of tumors, however, is hindered if the tumor is in close proximity to vital organs sensitive to overheating. Therefore, control over the heating process is of critical importance to ensure uniform and adequate heating of the tumor. We are currently developing an optically guided method to control and improve thermal ablation with temperature sensitive nanoparticles (nanothermometers). The principle of temperature sensitivity of the nanothermometers is based on thermally induced fluorescence. At a normal body temperature, the nanoparticles are invisible; upon heating, the nanoparticles generate fluorescence and become visible. The fluorescence signal will serve two purposes: 1) report the degree of ablation and 2) provide an optical map of the treated area.
On-Off activatable fluorescence probes for imaging
Our lab recently started developing fluorescence based imaging agents for lung related diseases. Pulmonary responses to acute lung injury are mediated through enhanced production of reactive oxygen species (ROS) and nitric oxide (NO) by alveolar macrophages. A continuous measurement of the ROS and NO level in vivo is critical for a prompt selection of an appropriate therapy and monitoring its outcome. We synthesize ROS and NO activatable fluorescent sensors by incorporating fluorophores into a nanoparticle polymethine platform. The sensors are designed to be completely quenched in the absence of the targeted molecule (ROS or NO). In the presence of the ROS or NO sensor fluorescence between 700 and 900 nm will be restored. This range is often used in in-vivo imaging due to the transparency of the tissue, thus providing a method for diagnosing lung pathologies and monitoring the effect of therapy.
Designing optically active molecules in the extended NIR region
To minimize the problem with scattering and absorption of photons in tissues while increasing the penetration depth we propose to use utilized the extended NIR (exNIR) dye with an optical range from 1000-1400 nm. This region is mostly free from water and other endogenous chromophores, leaving this optical window absorption transparent with virtually no autofluorescence. We are currently synthesizing targeted exNIR fluorescent dyes and nanoparticles with high quantum yield for in vivo imaging and building an exNIR imager.
Moscow Institute of Oil and Gas/Institute of Organic Chemistry, Academy of Science, Moscow, Russia, 1991, PhD, Chemistry
- Akers, W., Zhang, Z., Fuhrhop, R., Berezin, MY., Ye, Y. Agee, A., Guo, K., Lanza, G., Achilefu, S. Targeting of ανβ3-Integrins Expressed on Tumor Tissue and Neovasculature Using Fluorescent Small Molecules and Nanoparticles, Nanomedicine, 2010, 5 (5), 715-26, PMCID: PMC2914325
- Wang W., Zhegalova NG., Gustafson TP., Zhou A., Sher J., Achilefu S., Berezin OY., Berezin MY. Sensitivity of activatable reactive oxygen species probes by fluorescence spectroelectrochemistry, Analyst, 2013, 138, 4363-4369, PMCID: PMC3722072
- Magalotti S., Gustafson TP., Cao Q., Abendschein D., Pierce R., Berezin MY., Akers WJ. Evaluation of Inflammatory Response to Acute Ischemia Using Near-Infrared Fluorescent Reactive Oxygen Sensors, Mol Imaging Biol , 2013, 15 (4), page 423-430
- Gustafson,TP., Yan,P., Newton, P., Hunter, DA., Achilefu, S., Akers, WJ., Mackinnon, SE., Johnson., PJ and Berezin, MY. A NIR Dye for Development of Peripheral Nerve Targeted Probes, Med.Chem.Commun, 2012 2012,3, 685-690, PMID: 24575295 [PubMed] PMCID: PMC3932509
- Wood, MD., Berezin, MY, Akers, W., Mackinnon, SE, Molecular Imaging: The Future of Peripheral Nerve Injury Diagnosis, American Society for Peripheral Nerve Newsletter, 2013, 3 (5) p. 3
- Berezin, MY, Akers, W., Guo, K, Fischer, GM., Daltrozzo, E., Zumbusch, A., Achilefu, S. Long Fluorescence Lifetime Molecular Probes Based on Near Infrared Pyrrolopyrrole Cyanine Fluorophores for in vivo imaging, Biophys. J. 2009, 97, L22-L24 PMCID: PMC2770609
- Gustafson, TP., Cao Q., Achilefu, S., Berezin, MY. Defining a Polymethine Dye for Fluorescence Anisotropy Applications in the NIR Spectral Range, ChemPhysChem, 2012, 13(3):716-23 PMID: 22302715 [PubMed - indexed for MEDLINE] PMCID: PMC3969755
- Berezin MY, Achilefu S, Fluorescence Lifetime Measurements and Biological Imaging, Chem Rev. 2010 110(5): 2641–2684, PMCID: PMC2924670, NIHMSID: NIHMS220622
- Berezin MY, Guo K, Akers W, Livingston J, Solomon M, Lee H, Liang K, Agee A, Achilefu S, Rational Approach To Select Small Peptide Molecular Probes Labeled with Fluorescent Cyanine Dyes for in Vivo Optical Imaging, Biochemistry, 2011, PMCID: PMC3068226
- Zhegalova, NG., Gonzales, G., Berezin, MY., Synthesis of nitric oxide probes with fluorescence lifetime sensitivity, Org. Biomol. Chem., 2013, 11 (47), 8228 – 8234