title: Aminophthalocyanine-Mediated Photodynamic Inactivation of Leishmania tropica.
abstract: Photodynamic inactivation ofLeishmaniaspp. requires the cellular uptake of photosensitizers, e.g., endocytosis of silicon(IV)-phthalocyanines (PC) axially substituted with bulky ligands. We report here that when substituted with amino-containing ligands, the PCs (PC1 and PC2) were endocytosed and displayed improved potency againstLeishmania tropicapromastigotes and axenic amastigotesin vitro The uptake of these PCs by bothLeishmaniastages followed saturation kinetics, as expected. Sensitive assays were developed for assessing the photodynamic inactivation ofLeishmaniaspp. by rendering them fluorescent in two ways: transfecting promastigotes to express green fluorescent protein (GFP) and loading them with carboxyfluorescein succinimidyl ester (CFSE). PC-sensitizedLeishmania tropicastrains were seen microscopically to lose their motility, structural integrity, and GFP/CFSE fluorescence after exposure to red light (wavelength, ∼650 nm) at a fluence of 1 to 2 J cm(-2) Quantitative fluorescence assays based on the loss of GFP/CFSE from liveLeishmania tropicashowed that PC1 and PC2 dose dependently sensitized both stages for photoinactivation, consistent with the results of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay.Leishmania tropicastrains are >100 times more sensitive than their host cells or macrophages to PC1- and PC2-mediated photoinactivation, judging from the estimated 50% effective concentrations (EC50s) of these cells. Axial substitution of the PC with amino groups instead of other ligands appears to increase its leishmanial photolytic activity by up to 40-fold. PC1 and PC2 are thus potentially useful for photodynamic therapy of leishmaniasis and for oxidative photoinactivation ofLeishmaniaspp. for use as vaccines or vaccine carriers.
authors.affiliation: Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al-Qahtani
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Saad
authors.initials: S
authors.lastname: Alkahtani
authors.affiliation: Department of Microbiology/Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.
authors.forename: Bala
authors.initials: B
authors.lastname: Kolli
authors.affiliation: Department of Microbiology/Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Tripathi
authors.affiliation: Department of Microbiology/Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Dutta
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Abdullah A
authors.initials: AA
authors.lastname: Al-Kahtane
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong.
authors.forename: Xiong-Jie
authors.initials: XJ
authors.lastname: Jiang
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong.
authors.forename: Dennis K P
authors.initials: DK
authors.lastname: Ng
authors.affiliation: Department of Microbiology/Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA kwangpoo.chang@rosalindfranklin.edu.
authors.forename: Kwang Poo
authors.initials: KP
authors.lastname: Chang
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology*; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000494:pharmacology*; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D054833:Isoindoles; D007895:Leishmania tropica / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008018:Life Cycle Stages / Q000187:drug effects*; D008027:Light; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000378:metabolism
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000588:Amines; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007211:Indoles; D054833:Isoindoles; D017319:Photosensitizing Agents; D013388:Succinimides; D049452:Green Fluorescent Proteins; C013647:phthalocyanine
references.citation: Lasers Med Sci. 2015 Jan;30(1):347-54
references.pmid: 25288263
references.citation: Free Radic Biol Med. 2014 Dec;77:230-8
references.pmid: 25266330
references.citation: Br J Dermatol. 2015 May;172(5):1192-3
references.pmid: 25963215
references.citation: Expert Opin Drug Deliv. 2014 Apr;11(4):579-97
references.pmid: 24620861
references.citation: Antimicrob Agents Chemother. 2015 Sep;59(9):5804-13
references.pmid: 26169411
references.citation: J Biol Chem. 2002 Apr 26;277(17):14902-9
references.pmid: 11836252
references.citation: Int J Immunopathol Pharmacol. 2004 Sep-Dec;17(3):245-54
references.pmid: 15461858
references.citation: Mol Cell Biol. 1992 Sep;12(9):4112-22
references.pmid: 1324414
references.citation: Cancer Lett. 1995 Jul 13;93(2):255-9
references.pmid: 7621437
references.citation: Radiat Res. 1998 Nov;150(5 Suppl):S146-56
references.pmid: 9806617
references.citation: Antimicrob Agents Chemother. 2005 Nov;49(11):4474-84
references.pmid: 16251285
references.citation: Infect Immun. 2007 Feb;75(2):1017-24
references.pmid: 17118986
references.citation: Exp Parasitol. 2008 Apr;118(4):629-36
references.pmid: 18164705
references.citation: Eukaryot Cell. 2008 Jul;7(7):1146-57
references.pmid: 18487349
references.citation: Eur J Immunol. 2009 Jan;39(1):178-91
references.pmid: 19053149
references.citation: Dalton Trans. 2009 Jun 7;(21):4129-35
references.pmid: 19452061
references.citation: Mol Oncol. 2010 Jun;4(3):284-300
references.pmid: 20466604
references.citation: J Control Release. 2010 Nov 1;147(3):368-76
references.pmid: 20727925
references.citation: Expert Rev Anticancer Ther. 2010 Nov;10(11):1797-809
references.pmid: 21080805
references.citation: Methods Mol Biol. 2011;720:309-26
references.pmid: 21318882
references.citation: PLoS One. 2011;6(6):e20786
references.pmid: 21673971
references.citation: Exp Parasitol. 2011 Aug;128(4):353-6
references.pmid: 21575635
references.citation: J Med Chem. 2011 Jan 13;54(1):320-30
references.pmid: 21138268
references.citation: Photodermatol Photoimmunol Photomed. 2011 Oct;27(5):254-6
references.pmid: 21950631
references.citation: Lasers Surg Med. 2011 Sep;43(7):755-67
references.pmid: 22057503
references.citation: Eukaryot Cell. 2012 Apr;11(4):430-41
references.pmid: 22307976
references.citation: Photochem Photobiol. 2012 May-Jun;88(3):620-5
references.pmid: 22211765
references.citation: J Photochem Photobiol B. 2012 Dec 5;117:157-63
references.pmid: 23123595
references.citation: Lasers Surg Med. 2012 Dec;44(10):850-5
references.pmid: 23184450
references.citation: Br J Dermatol. 2015;172(5):1364-70
references.pmid: 25363817