Photo of Brian Polizzotti,  PhD

Brian Polizzotti, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-4693


brian.polizzotti@childrens.harvard.edu

Brian Polizzotti, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Pediatrics, Harvard Medical School
  • Staff Scientist, Cardiology, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Hypoxia is recognized as a major factor contributing to radioresistance, and in prostate cancer, is directly associated with shorter times to biochemical relapse and metastasis. Radiation therapy generates radical DNA species that are readily reversible under hypoxic conditions; however, oxygen chemically fixes this damage by oxidizing the DNA radicals to yield peroxides that ultimately result in DNA strand breaks and cell death. This renders hypoxic tumors ~3x more resistant to radiation than well oxygenated ones. Attempts to improve tumor oxygenation by altering the oxygen carrying capacity of blood (i.e. hyperbaric oxygen, respiratory hyperoxia, and carbogen, hemoglobin-based agents and perfluorocabon based emulsions) have had limited success in various clinical trials, and is most likely due to an abnormal tumor microenvironment. Our laboratory has pioneered the fabrication of polymer-shelled hollow microparticles (PHMs) that can rapidly load and release concentrated oxygen at controlled rates in response to changes in the partial pressure of the surrounding fluid. We are interested in using these systems to actively reverse tumor hypoxia during radiotherapy.

Publications

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  • Black KJ, Lock AT, Thomson LM, Cole AR, Tang X, Polizzotti BD, Kheir JN. Hemodynamic Effects of Lipid-Based Oxygen Microbubbles via Rapid Intravenous Injection in Rodents. 2017. PubMed
  • Kheir JN, Polizzotti BD. Reply to Span et al.: Rational design of oxygen microparticles for radiation therapy. Proc Natl Acad Sci U S A 2016; 113:E8010. PubMed
  • Seekell RP, Lock AT, Peng Y, Cole AR, Perry DA, Kheir JN, Polizzotti BD. Oxygen delivery using engineered microparticles. Proc Natl Acad Sci U S A 2016; 113:12380-12385. PubMed
  • Polizzotti BD, Ganapathy B, Haubner BJ, Penninger JM, Kühn B. A cryoinjury model in neonatal mice for cardiac translational and regeneration research. Nat Protoc 2016; 11:542-52. PubMed
  • Ganapathy B, Nandhagopal N, Polizzotti BD, Bennett D, Asan A, Wu Y, Kühn B. Neuregulin-1 Administration Protocols Sufficient for Stimulating Cardiac Regeneration in Young Mice Do Not Induce Somatic, Organ, or Neoplastic Growth. PLoS ONE 2016; 11:e0155456. PubMed
  • Polizzotti BD, Ganapathy B, Walsh S, Choudhury S, Ammanamanchi N, Bennett DG, Dos Remedios CG, Haubner BJ, Penninger JM, Kühn B. Neuregulin stimulation of cardiomyocyte regeneration in mice and human myocardium reveals a therapeutic window. Sci Transl Med 2015; 7:281ra45. PubMed
  • Polizzotti BD, Thomson LM, O'Connell DW, McGowan FX, Kheir JN. Optimization and characterization of stable lipid-based, oxygen-filled microbubbles by mixture design. J. Biomed. Mater. Res. Part B Appl. Biomater. 2014; 102:1148-56. PubMed
  • Thomson LM, Polizzotti BD, McGowan FX, Kheir JN. Manufacture of concentrated, lipid-based oxygen microbubble emulsions by high shear homogenization and serial concentration. 2014. PubMed
  • Bersell K, Choudhury S, Mollova M, Polizzotti BD, Ganapathy B, Walsh S, Wadugu B, Arab S, Kühn B. Moderate and high amounts of tamoxifen in αMHC-MerCreMer mice induce a DNA damage response, leading to heart failure and death. Dis Model Mech 2013; 6:1459-69. PubMed
  • Kheir JN, Polizzotti BD, Thomson LM, O'Connell DW, Black KJ, Lee RW, Wilking JN, Graham AC, Bell DC, McGowan FX. Bulk manufacture of concentrated oxygen gas-filled microparticles for intravenous oxygen delivery. Adv Healthc Mater 2013; 2:1131-41. PubMed
  • Polizzotti BD, Arab S, Kühn B. Intrapericardial delivery of gelfoam enables the targeted delivery of periostin Peptide after myocardial infarction by inducing fibrin clot formation. PLoS ONE 2012; 7:e36788. PubMed
  • DeForest CA, Polizzotti BD, Anseth KS. Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments. Nat Mater 2009; 8:659-64. PubMed
  • Polizzotti BD, Fairbanks BD, Anseth KS. Three-dimensional biochemical patterning of click-based composite hydrogels via thiolene photopolymerization. Biomacromolecules 2008; 9:1084-7. PubMed
  • Polizzotti BD, Maheshwari R, Vinkenborg J, Kiick KL. Effects of Saccharide Spacing and Chain Extension on Toxin Inhibition by Glycopolypeptides of Well-Defined Architecture. Macromolecules 2011; 40:7103-7110. PubMed
  • Polizzotti BD, Kiick KL. Effects of polymer structure on the inhibition of cholera toxin by linear polypeptide-based glycopolymers. Biomacromolecules 2006; 7:483-90. PubMed
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