We are performing mechanistic studies of new bacteriochlorin and fullerene photosynthesizers, and have collaborated with chemistry groups at various institutions to test newly synthesized potential photosensitizers in various biomedical applications. In collaboration with Tim Wharton and Lynntech, Inc. in Texas, and also with Long Chiang, at U Mass Lowell we are exploring the use of fullerenes as anticancer and antimicrobial photosensitizers. Fullerenes are based on the recently discovered allotrope of carbon (C60 cages) that have been chemically modified to dramatically improve their performance in PDT applications.
In collaboration with Professor Jon Lindsey at NCSU and NIRvana Pharmaceuticals we also study stable fully synthetic bacteriochlorin photosensitizers that have high optical absorbance in the near-infrared region of the spectrum (700-900-nm) where tissue penetration of light is maximal. Insertion of metal atoms into the central position of tetrapyrroles such as bacteriochlorins may change their photophysical properties and alter the photochemical pathways that proceed from the triplet state.
These studies have involved developing new assays for various kinds of reactive oxygen species (singlet oxygen, superoxide, hydroxyl radical, hydroperoxides) that appear to be involved in the cytotoxic effects.
Tegos GP, Demidova TN, Arcila-Lopez D, Lee H, Gali H, Wharton T, Hamblin MR . Cationic fullerenes are effective and selective antimicrobial photosensitizers. Chem Biol, 2005, 12: 1127-1135
Borbas KE, Mroz P, Hamblin MR, and Lindsey JS. Bioconjugatable porphyrins bearing a compact swallowtail motif for water solubility. Bioconj Chem, 2006, 17: 638-653
Mroz P, Pawlak A, Satti M, Lee H, Wharton T, Gali H, Sarna T and Hamblin MR. Functionalized fullerenes mediate photodynamic killing of cancer cells: Type I versus Type II photochemical mechanism. Free Radical Biol Med, 2007 Sep 1;43(5):711-9.
Mroz P, Tegos GP, Gali H, Wharton T, Sarna T, Hamblin MR, Photodynamic therapy with fullerenes, Photochem Photobiol Sci, 2007, 6, 1139 - 1149
Kee HL, Bhaumik J, Diers JR, Mroz P, Hamblin MR, Bocian DF, Lindsey JS, Holten D. Photophysical characterization of imidazolium-substituted Pd(II), In(III), and Zn(II) porphyrins as photosensitizers for photodynamic therapy. J Photochem Photobiol A, 2008, 200: 346–355.
Mroz P, Bhaumik J, Aly Z, Kamal Z, Khalid L, Kee HL, Bocian DF, Holten D, Lindsey JS, Hamblin MR, Imidazole metalloporphyrins as photosensitizers for photodynamic therapy: role of molecular charge, central metal and hydroxyl radical production. Cancer Lett, 2009. 282:63-76
Mroz P, Huang YY, Szokalska A, Zhiyentayev T, Janjua S, Nifli AP,. Sherwood ME, Ruzié C, Borbas KE, Fan D, Krayer M, Balasubramanian T, Yang E, Kee HL, Kirmaier C, Diers JR, Bocian DF, Holten D, Lindsey JS, Hamblin MR. Innovative stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy. FASEB J, 2010, 24, 3160–3170
Chen Z, Zhou S, Chen J, Deng Y, Luo Z, Chen H, Hamblin MR, Huang M. Pentalysine b-Carbonylphthalocyanine Zinc: An Effective Tumor-Targeting Photosensitizer for Photodynamic Therapy. ChemMedChem, 2010, 5(6):890-8.
Huang L , Terakawa M, Zhiyentayev T, Huang Y-Y, Sawayama, Y, Jahnke A, Tegos, GP, Wharton T, Hamblin MR. Innovative cationic fullerenes as broad-spectrum light-activated antimicrobials. Nanomedicine: Nanotechnology, Biology, and Medicine, 2010, 6(3), 442 – 452.
Huang YY, Mroz P, Zhiyentayev T, Sharma SK, Balasubramanian T, Ruzié C, Borbas KE, Fan D, Krayer M, Yang E, Kee HL, Kirmaier C, Diers JR, Bocian DF, Holten D, Lindsey JS, Hamblin MR. In Vitro Photodynamic Therapy and Quantitative Structure-Activity Relationship Studies with Stable Synthetic Near-Infrared-Absorbing Bacteriochlorin Photosensitizers. J Med Chem, 2010, 53(10):4018-27
Huang L, Huang YY, Mroz P, Tegos GP, Zhiyentayev T, Sharma SK, Lu Z, Balasubramanian T, Krayer M, Ruzié C, Yang E, Kee HL, Kirmaier C, Diers JR, Bocian DF, Holten D, Lindsey JS, Hamblin MR. Stable Synthetic Cationic Bacteriochlorins As Selective Antimicrobial Photosensitizers. Antimicrob Agents Chemother, 2010, 54; 3834–3841
Chiang LY, Padmawar PA, Rogers-Haley JE, So G, Canteenwala T, Thota S, Tan LS, Pritzker K, Huang YY, Sharma SK, Kurup DB, Hamblin, MR. Wilson BC, Urbas A. Synthesis and characterization of highly photoresponsive fullerenyl dyads with a close chromophore antenna–C60 contact and effective photodynamic potential. J Mater. Chem., 2010, 20, 5280 – 5293
Ragàs X, Sánchez-García D, Ruiz-González R, Dai T, Agut M, Hamblin MR, Nonell S. Cationic Porphycenes as Potential Photosensitizers for Antimicrobial Photodynamic Therapy. J Med Chem. 2010, 53(21):7796-7803.
Lu Z, Dai T, Huang L, Kurup DB, Tegos GP, Jahnke A, Wharton T, Hamblin, MR. Photodynamic therapy with a cationic functionalized fullerene rescues mice from fatal wound infections. Nanomedicine UK. 2010; 5(10):1525-33.
Mroz P, Xia Y, Asanuma D, Konopko A, Zhiyentayev T, Huang YY, Sharma SK, Dai T, Khan UJ, Wharton T, Hamblin MR, Intraperitoneal photodynamic therapy mediated by a fullerene in a mouse model of abdominal dissemination of colon adenocarcinoma. Nanomedicine, 2011, 7(6):965-74.
Mizuno K, Zhiyentayev T, Huang L, Khalil1 S, Nasim F, Tegos GP, Gali H, Jahnke A, Wharton T, Hamblin MR. Antimicrobial photodynamic therapy with functionalized fullerenes: Quantitative structure-activity relationships. J Nanomedic Nanotechnol 2011, 2:2 http://dx.doi.org/10.4172/2157-7439.1000109.
Sharma SK Chiang LY, Hamblin MR, Photodynamic therapy with fullerenes in vivo: reality or a dream? Nanomedicine (UK), 2011, Dec;6(10):1813-25.
Huang YY, Sharma SK, Dai T, Chung H, Yaroslavsky A, Garcia-Diaz M, Chang J, Chiang LY, Hamblin MR, Can Nanotechnology Potentiate Photodynamic Therapy? Nanotech Rev, 2012, 1(2), 111-146. doi: 10.1515/ntrev-2011-0005
Li P, Zhou G, Zhu X, Li G, Yan P, Shen L, Xu Q, Hamblin MR. Photodynamic therapy with hyperbranched poly(ether-ester) chlorin(e6) nanoparticles on human tongue carcinoma CAL-27 cells. Photodiagnosis Photodyn Ther. 2012 Mar;9(1):76-82.
Wang M, Huang L, Sharma SK, Jeon S, Thota S, Sperandio FF, Nayka S, Chang J, Hamblin MR, Chiang LY. Synthesis and photodynamic effect of new highly photostable decacationically armed - and fullerene decaiodide monoadducts to target pathogenic bacteria and cancer cells. J Med Chem. 2012 May 10;55(9):4274-85.
Thota S, Wang M, Jeon S, Maragani S, Hamblin MR, Chiang LY. Synthesis and characterization of positively charged pentacationic fullerene monoadducts for antimicrobial photodynamic inactivation. Molecules. 2012 May 7;17(5):5225-43.
García-Díaz M, Kawakubo M, Mroz P, Sagristà ML, Mora M, Nonell S, Hamblin MR. Cellular and vascular effects of the photodynamic agent temocene are modulated by the delivery vehicle. J Control Release, 2012 Sep 10;162(2):355-63.