Linked Life Data

15034722

Source:http://linkedlifedata.com/resource/pubmed/id/15034722

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-5-12
pubmed:abstractText
The subcellular localization, efficacy and photooxidative mechanism of three new photosensitizing porphycenes (HexoTMPn, PeloTMPn, CpoTMPn) for photodynamic therapy with different substituents at position 9 of the tetrapyrrole macrocycle were investigated in vitro using different human skin-derived cell lines (HaCaT, SCL I, SCL II) with the aim of customizing the side-chain chemistry to accelerate cellular uptake and so enhance photodynamic activity. Cells were incubated with a porphycene and costained with organelle-specific markers. Subcellular localization was determined by fluorescence microscopy. Also, cells were incubated with different sensitizer concentrations (0-1000 nmol/l) and irradiated by an incoherent light source (lambda(em) = 600-750 nm, 40 mW/cm(2), 24 J/cm(2)) with/without quenchers or enhancers (NaN(3), histidine, mannitol or D(2)O). Cell viability was assessed. All porphycenes were localized in perinuclear lysosomes and induced a decrease in mitochondrial activity following irradiation. HexoTMPn was the most efficient in all three cell lines (EC(50) in HaCaT cells: HexoTMPn 14 nmol/l, CpoTMPn 62 nmol/l, PeloTMPn 89 nmol/l). Addition of either NaN(3) or histidine reduced the phototoxicity significantly. Due to the short lifetime of singlet oxygen, the sites of sensitizer localization are the initial subcellular targets. The cytotoxicity of each sensitizer varied depending on singlet oxygen quantum yield and cell line. Despite the different chemical structures, the biological effects were not very distinct, since they seemed to be mostly determined by the tetrapyrrole ring and only slightly modified by the substituent at position 9. Also, there was only a narrow margin between biological compatibility and efficacy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0340-3696
pubmed:author
pubmed:issnType
Print
pubmed:volume
295
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
535-41
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Structure-activity relationships of three differently substituted 2,7,12,17-tetrakis-(beta-methoxyethyl) porphycene derivatives in vitro.
pubmed:affiliation
Department of Dermatology, University of Regensburg, 93042 Regensburg, Germany.
pubmed:publicationType
Journal Article