Linked Life Data

10328226

Source:http://linkedlifedata.com/resource/pubmed/id/10328226

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-6-25
pubmed:abstractText
Photosensitizers, molecules that produce active oxygen species upon activation by visible light, are currently being used in photodynamic therapy (PDT) to treat cancer and other conditions, where limitations include normal cells and tissue damage and associated side effects, and the fact that cytotoxic effects are largely restricted to the plasma and other peripheral membranes. In this study, we used insulin-containing conjugates to which variants of the simian-virus-SV40 large-tumor antigen (T-ag) nuclear localization signal (NLS) were linked in order to target the photosensitizer chlorin e6 to the nucleus. NLSs were included either as peptides coupled co-valently to the carrier bovine serum albumin, or within the coding sequence of beta-galactosidase fusion proteins. The most potent photosensitizing conjugate was the NLS-containing T-ag beta-galactosidase fusion protein (P10)-(chlorin e6)-insulin, exhibiting an EC50 more than 2400-fold lower than the value for free chlorin e6, and more than 15-fold lower than that of an NLS-deficient beta-galactosidase-(chlorin e6)-insulin construct, thus demonstrating that NLSs can increase the photosensitizing activity of chlorin e6. Attenuated adenoviruses were used to increase the nuclear delivery of conjugates through its endosomal-membrane-disrupting activity. In the case of the NLS-containing P10-conjugate, co-incubation with adenovirus increased the proportion of cells whose nuclear photosensitizing activity was higher than that in the cytoplasm by 2.5-fold. This use of adenoviruses in conjunction with photosensitizers has clear implications for achieving efficient cell-type-specific PDT.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
734-40
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Adenoviruses synergize with nuclear localization signals to enhance nuclear delivery and photodynamic action of internalizable conjugates containing chlorin e6.
pubmed:affiliation
Biophysical Laboratory, Russian Institute of Agricultural Biotechnology, Moscow.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't