Abstract:
:The effect of charge on the cellular uptake, localization and phototoxicity of conjugates between chlorin(e6) (ce6) and poly-L-lysine was studied in vitro. These conjugates (average MW 35-55 kDa) were synthesized to have polycationic, polyanionic or neutral charges. Two human cell lines (A431 epidermoid carcinoma cells and EA.hy926 hybrid endothelial cells) were studied and the cellular uptake of ce6 delivered by the conjugates of varying charge and free ce6 was measured at conjugate ce6 equivalent concentrations up to 0.4 microM. Uptake was time and concentration dependent and temperature dependent in the case of neutral and anionic conjugates. Relative uptake at 6 h for A431 cells was 73:15:4:1 and for EA.hy926 cells was 63:11:3:1 for cationic, anionic, neutral and free ce67 respectively, but EA.hy926 cells took up 1.5-2 times as much ce6 from all the conjugates as A431 cells. Localization as studied by fluorescence microscopy indicated that the cationic conjugate was in aggregates bound to the plasma membrane, while the other forms were internalized in organelles and membranes. Phototoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) assay after irradiation with 5-20 J cm2 of 666 nm light. In contrast to the uptake, the order of phototoxicity for both cell types per mole of ce6 uptake per cell was neutral > anionic > cationic > free ce6. Polymeric ce6 conjugates bearing positive, negative and neutral charges may have different tissue-localizing properties and could play a role in photodynamic therapy.
journal_name
Photochem Photobioljournal_title
Photochemistry and photobiologyauthors
Soukos NS,Hamblin MR,Hasan Tdoi
10.1111/j.1751-1097.1997.tb01916.xsubject
Has Abstractpub_date
1997-04-01 00:00:00pages
723-9issue
4eissn
0031-8655issn
1751-1097journal_volume
65pub_type
杂志文章abstract::The XPA gene-deficient mouse, an animal model of xeroderma pigmentosum (XP), develops enhanced photobiologic reactions including acute inflammation, immunosuppression and skin carcinogenesis, because of the defect in the excision repair of ultraviolet-induced DNA lesions. The results strongly suggest that nuclear DNA ...
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