Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2010-7-14
pubmed:abstractText
Cisplatin is a first line chemotherapy for most types of cancer. However, its use is dose-limited due to severe nephrotoxicity. Here we report the rational engineering of a novel nanoplatinate inspired by the mechanisms underlying cisplatin bioactivation. We engineered a novel polymer, glucosamine-functionalized polyisobutylene-maleic acid, where platinum (Pt) can be complexed to the monomeric units using a monocarboxylato and an O --> Pt coordinate bond. We show that at a unique platinum to polymer ratio, this complex self-assembles into a nanoparticle, which releases cisplatin in a pH-dependent manner. The nanoparticles are rapidly internalized into the endolysosomal compartment of cancer cells, and exhibit an IC50 (4.25 +/- 0.16 microM) comparable to that of free cisplatin (3.87 +/- 0.37 microM), and superior to carboplatin (14.75 +/- 0.38 microM). The nanoparticles exhibited significantly improved antitumor efficacy in terms of tumor growth delay in breast and lung cancers and tumor regression in a K-ras(LSL/+)/Pten(fl/fl) ovarian cancer model. Furthermore, the nanoparticle treatment resulted in reduced systemic and nephrotoxicity, validated by decreased biodistribution of platinum to the kidney as quantified using inductively coupled plasma spectroscopy. Given the universal need for a better platinate, we anticipate this coupling of nanotechnology and structure-activity relationship to rationally reengineer cisplatin could have a major impact globally in the clinical treatment of cancer.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-10458260, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-11151361, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-11156411, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-11356986, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-12086869, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-14728945, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-15161693, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-15619626, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-15738981, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-15807631, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-16489089, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-17446929, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-17625587, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-17891134, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-18697944, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-18712584, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-18978032, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-19009590, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-20043662, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-3512077, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-7641188, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-8012948, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-8088411, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-8525382, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-8932544, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-9506354, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-9605750, http://linkedlifedata.com/resource/pubmed/commentcorrection/20616005-99034
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
13
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12435-40
pubmed:dateRevised
2010-9-30
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Harnessing structure-activity relationship to engineer a cisplatin nanoparticle for enhanced antitumor efficacy.
pubmed:affiliation
Department of Medicine, Brigham and Women's Hospital, Cambridge, MA 02139, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural