Alexander L. Klibanov

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Primary Appointment

Associate Professor, Medicine- Cardiovascular Medicine

Education

  • MS, Chemistry, Moscow State University, Moscow Russia
  • PhD, Biochemistry, USSR Cardiology Research Center, Moscow, Russia

Research Interests

Targeted delivery of therapeutic and diagnostic imaging agents.

Research Description

Ultrasound imaging is a widespread and inexpensive non-invasive diagnostic technique. Ultrasound contrast agents offer a flexible platform that can be used for diagnostic imaging as a blood pool marker (tissue perfusion), as a targeted marker for imaging of inflammation, angiogenesis, and also as adjunct microdevices for enhanced targeted drug delivery and gene therapy.
In diagnostic imaging, detection of contrast material offers high sensitivity (individual micron-sized particles can be visualized in vitro and in vivo by ultrasound medical imaging systems). We prepare and analyze such ultrasound contrast materials, attach targeting ligands (antibodies, peptides) and plasmid DNA to their surface for targeting and ultrasound-enhanced delivery. Using colloid chemistry-based approaches, stable microbubbles with extended circulation lifetime are designed; polymer brush coating is applied to ensure enhanced stability.

Personal Statement

Ultrasound imaging is a widespread and inexpensive non-invasive diagnostic technique. Ultrasound contrast agents offer a flexible platform that can be used for diagnostic imaging as a blood pool marker (tissue perfusion), as a targeted marker for imaging of inflammation, angiogenesis, and also as adjunct microdevices for enhanced targeted drug delivery and gene therapy. In diagnostic imaging, detection of contrast material offers high sensitivity (individual micron-sized particles can be visualized in vitro and in vivo by ultrasound medical imaging systems). We prepare and analyze such ultrasound contrast materials, attach targeting ligands (antibodies, peptides) and plasmid DNA to their surface for targeting and ultrasound-enhanced delivery. Using colloid chemistry-based approaches, stable microbubbles with extended circulation lifetime are designed; polymer brush coating is applied to ensure enhanced stability.

Selected Publications

Rychak JJ, Klibanov AL, Nucleic acid delivery with microbubbles and ultrasound., 2014; Advanced drug delivery reviews. 72() 82-93. PMID: 24486388

Erdbrügger U, Rudy CK, E Etter M, Dryden KA, Yeager M, Klibanov AL, Lannigan J, Imaging flow cytometry elucidates limitations of microparticle analysis by conventional flow cytometry., 2014; Cytometry. Part A : the journal of the International Society for Analytical Cytology. 85(9) 756-70. PMID: 24903900

Kilroy JP, Klibanov AL, Wamhoff BR, Bowles DK, Hossack JA, Localized in Vivo Model Drug Delivery with Intravascular Ultrasound and Microbubbles., 2014; Ultrasound in medicine & biology. 40(10) 2458-67. PMID: 25130449

Wang S, Mauldin FW, Klibanov AL, Hossack JA, Shear forces from flow are responsible for a distinct statistical signature of adherent microbubbles in large vessels., 2013; Molecular imaging. 12(6) 396-408. PMID: 23981785 | PMCID: PMC4061764

Wang S, Hossack JA, Klibanov AL, Mauldin FW, Binding dynamics of targeted microbubbles in response to modulated acoustic radiation force., 2013; Physics in medicine and biology. 59(2) 465-84. PMID: 24374866 | PMCID: PMC4068277

Kilroy JP, Klibanov AL, Wamhoff BR, Hossack J, Intravascular ultrasound catheter to enhance microbubble-based drug delivery via acoustic radiation force., 2012; IEEE transactions on ultrasonics, ferroelectrics, and frequency control. 59(10) 2156-66. PMID: 23143566

Naresh NK, Xu Y, Klibanov AL, Vandsburger MH, Meyer CH, Leor J, Kramer CM, French BA, Epstein FH, Monocyte and/or macrophage infiltration of heart after myocardial infarction: MR imaging by using T1-shortening liposomes., 2012; Radiology. 264(2) 428-35. PMID: 22723500 | PMCID: PMC3401349

Burke CW, Suk JS, Kim AJ, Hsiang YH, Klibanov AL, Hanes J, Price RJ, Markedly enhanced skeletal muscle transfection achieved by the ultrasound-targeted delivery of non-viral gene nanocarriers with microbubbles., 2012; Journal of controlled release : official journal of the Controlled Release Society. 162(2) 414-21. PMID: 22800583 | PMCID: PMC3438364

Unnikrishnan S, Klibanov AL, Microbubbles as ultrasound contrast agents for molecular imaging: preparation and application., 2012; AJR. American journal of roentgenology. 199(2) 292-9. PMID: 22826389

Phillips LC, Klibanov AL, Wamhoff BR, Hossack JA, Localized ultrasound enhances delivery of rapamycin from microbubbles to prevent smooth muscle proliferation., 2011; Journal of controlled release : official journal of the Controlled Release Society. 154(1) 42-9. PMID: 21549778 | PMCID: PMC3148278

Burke CW, Klibanov AL, Sheehan JP, Price RJ, Inhibition of glioma growth by microbubble activation in a subcutaneous model using low duty cycle ultrasound without significant heating., 2011; Journal of neurosurgery. 114(6) 1654-61. PMID: 21214331

Patil AV, Rychak JJ, Klibanov AL, Hossack JA, Real-time technique for improving molecular imaging and guiding drug delivery in large blood vessels: in vitro and ex vivo results., 2011; Molecular imaging. 10(4) 238-47. PMID: 21521555 | PMCID: PMC3127411

Phillips LC, Dhanaliwala AH, Klibanov AL, Hossack JA, Wamhoff BR, Focused ultrasound-mediated drug delivery from microbubbles reduces drug dose necessary for therapeutic effect on neointima formation--brief report., 2011; Arteriosclerosis, thrombosis, and vascular biology. 31(12) 2853-5. PMID: 21960561 | PMCID: NIHMS332721

Phillips LC, Klibanov AL, Wamhoff BR, Hossack JA, Targeted gene transfection from microbubbles into vascular smooth muscle cells using focused, ultrasound-mediated delivery., 2010; Ultrasound in medicine & biology. 36(9) 1470-80. PMID: 20800174 | PMCID: PMC2930891

Tlaxca JL, Anderson CR, Klibanov AL, Lowrey B, Hossack JA, Alexander JS, Lawrence MB, Rychak JJ, Analysis of in vitro transfection by sonoporation using cationic and neutral microbubbles., 2010; Ultrasound in medicine & biology. 36(11) 1907-18. PMID: 20800945 | PMCID: PMC2996233

Ferrante EA, Pickard JE, Rychak J, Klibanov A, Ley K, Dual targeting improves microbubble contrast agent adhesion to VCAM-1 and P-selectin under flow., 2009; Journal of controlled release : official journal of the Controlled Release Society. 140(2) 100-7. PMID: 19666063 | PMCID: PMC2783796

Patil AV, Rychak JJ, Allen JS, Klibanov AL, Hossack JA, Dual frequency method for simultaneous translation and real-time imaging of ultrasound contrast agents within large blood vessels., 2009; Ultrasound in medicine & biology. 35(12) 2021-30. PMID: 19828229 | PMCID: PMC2790010

Phillips LC, Klibanov AL, Bowles DK, Ragosta M, Hossack JA, Wamhoff BR, Focused in vivo delivery of plasmid DNA to the porcine vascular wall via intravascular ultrasound destruction of microbubbles., 2009; Journal of vascular research. 47(3) 270-4. PMID: 19923850 | PMCID: PMC2865392

Hernot S, Klibanov AL, Microbubbles in ultrasound-triggered drug and gene delivery., 2008; Advanced drug delivery reviews. 60(10) 1153-66. PMID: 18486268 | PMCID: PMC2720159

Chappell JC, Song J, Burke CW, Klibanov AL, Price RJ, Targeted delivery of nanoparticles bearing fibroblast growth factor-2 by ultrasonic microbubble destruction for therapeutic arteriogenesis., 2008; Small (Weinheim an der Bergstrasse, Germany). 4(10) 1769-77. PMID: 18720443 | PMCID: PMC2716217

Song J, Klibanov AL, Hossack JA, Price RJ, Acoustic attenuation by contrast agent microbubbles in superficial tissue markedly diminishes petechiae bioeffects in deep tissue., 2008; Investigative radiology. 43(5) 322-9. PMID: 18424953 | PMCID: PMC2714264