DF/HCC Program Affiliation

Gynecologic Cancer

Research Abstract

Photodynamic therapy is a relatively new and exciting approach for treating cancers and other diseases. Many new photosensitizers have been developed in recent years, but it is still not clear what is the basic mechanism of the tumor localizing effect, and hence the optimum structure and formulation of the photosensitizer for any particular application is uncertain.

My particular area of interest is in the preparation and investigation of macromolecular conjugates of photosensitizers. Large molecules have very different biodistribution and pharmacokinetics compared to the small molecules which are generally used as photosensitizers. In addition it may be possible to use conjugates of photosensitizers with specifically targeted macromolecules to cancer cells and other defined cells and organs. I am also interested in the use of PDT to generate long-term specific anti-tumor immunity in immunocompetent mouse tumor models, and its relation to specific PDT parameters.

Examples of the above approaches are,

(a) the use of monoclonal antibody photosensitizer conjugates directed towards tumor associated antigens to target metastatic ovarian and colorectal cancer.

(b) the use of conjugates with polyamino acids which can vary in size, charge and hydrophobicity and can therefore produce different pharmacokinetics, biodistributions and enhanced phototoxicities.

(c) targeting pathogenic bacteria which may produce wound infections or other diseases with polycationic photosensitizer conjugates

(d) the use of conjugates with serum proteins such as albumin and lipoproteins which could have improved tumor targeting properties and specificity for macrophage type cells.

(e) the use of macromolecular conjugates to direct photosensitizers to subcellular locations such as lysosomes, mitochondria and membranes, where they could either increase the cytotoxic effect, or conversely not kill the cell but induce it to express cytokines or growth factors which could be advantageous in such areas as wound healing.

Publications

• Demidova-Rice TN, Salomatina EV, Yaroslavsky AN, Herman IM, Hamblin MR.Low-level light stimulates excisional wound healing in mice.Lasers Surg Med 2007 Oct;39(9):706-15.
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• Castano AP, Dai T, Yaroslavsky I, Cohen R, Apruzzese WA, Smotrich MH, Hamblin MR.Low-level laser therapy for zymosan-induced arthritis in rats: Importance of illumination time.Lasers Surg Med 2007 Jul;39(6):543-50.
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• Tegos GP, Demidova TN, Arcila-Lopez D, Lee H, Wharton T, Gali H, Hamblin MR.Cationic fullerenes are effective and selective antimicrobial photosensitizers.Chem Biol 2005 Oct;12(10):1127-35.
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• Hamblin MR, Viveiros J, Yang C, Ahmadi A, Ganz RA, Tolkoff MJ.Helicobacter pylori accumulates photoactive porphyrins and is killed by visible light.Antimicrob Agents Chemother 2005 Jul;49(7):2822-7.
  15980355
• Shi L, Takahashi K, Dundee J, Shahroor-Karni S, Thiel S, Jensenius JC, Gad F, Hamblin MR, Sastry KN, Ezekowitz RA.Mannose-binding Lectin-deficient Mice Are Susceptible to Infection with Staphylococcus aureus.J Exp Med 2004 May 17;199(10):1379-90.
  15148336
• Hamblin MR, Hasan T.Photodynamic therapy: a new antimicrobial approach to infectious disease?.Photochem Photobiol Sci 2004 May;3(5):436-50.
  15122361
• Hamblin MR, Miller JL, Rizvi I, Ortel B, Maytin EV, Hasan T.Pegylation of a chlorin(e6) polymer conjugate increases tumor targeting of photosensitizer.Cancer Res 2001 Oct 1;61(19):7155-62.
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• Hamblin MR, Miller JL, Ortel B.Scavenger-receptor targeted photodynamic therapy.Photochem Photobiol 2000 Oct;72(4):533-40.
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