Linked Life Data

21417439

Source:http://linkedlifedata.com/resource/pubmed/id/21417439

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-6-6
pubmed:abstractText
The clinical development of siRNA cancer therapeutics is limited by the poor interstitial transport and inefficient transfection in solid tumors. We have shown that paclitaxel pretreatment, by inducing apoptosis, causes expansion of the interstitial space and thereby improves nanoparticle delivery and transport in tumor interstitium (referred to as paclitaxel tumor priming) and efficacy of nanomedicines in tumor-bearing animals. The present study evaluated whether paclitaxel tumor priming improves the delivery and transfection of siRNA in 2- and 3-dimensional cultures of human oropharyngeal carcinoma FaDu cells. We used the fluorescent siGLO and confocal microcopy to monitor transport, and used survivin siRNA and immunostaining and immunoblotting to monitor transfection. Survivin is a chemoresistance gene/protein, inducible by chemotherapy. siRNA was loaded in cationic liposomes. The results showed that pretreatment with 50-200 nM paclitaxel (24 or 48 h before siRNA) enhanced the total uptake of siGLO into monolayers (?15%, p < 0.05), and the depth of penetration into 3-dimensional spheroids and tumor fragment histocultures (2.1- to 2.5-times greater area under the penetration-depth curve). In both monolayer cells and histocultures, paclitaxel pretreatment induced survivin upregulation (p < 0.05). Survivin siRNA alone decreased the survivin levels in a dose-dependent manner, and applying survivin siRNA after paclitaxel pretreatment completely abolished the paclitaxel-induced survivin increases. These findings indicate that paclitaxel tumor priming did not compromise the siRNA functionality. In summary, paclitaxel tumor priming improved the penetration, transfection and functionality of siRNA in tumors, thus offering a promising and practical means to develop chemo-siRNA cancer gene therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1543-8392
pubmed:author
pubmed:issnType
Electronic
pubmed:day
6
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
833-40
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Paclitaxel tumor-priming enhances siRNA delivery and transfection in 3-dimensional tumor cultures.
pubmed:affiliation
College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural