Publication Date:
2010-04-10
Description:
Poor penetration of anticancer drugs into tumors can be an important factor limiting their efficacy. We studied mouse tumor models to show that a previously characterized tumor-penetrating peptide, iRGD, increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing coadministered drugs to penetrate into extravascular tumor tissue. Importantly, this effect did not require the drugs to be chemically conjugated to the peptide. Systemic injection with iRGD improved the therapeutic index of drugs of various compositions, including a small molecule (doxorubicin), nanoparticles (nab-paclitaxel and doxorubicin liposomes), and a monoclonal antibody (trastuzumab). Thus, coadministration of iRGD may be a valuable way to enhance the efficacy of anticancer drugs while reducing their side effects, a primary goal of cancer therapy research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881692/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881692/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sugahara, Kazuki N -- Teesalu, Tambet -- Karmali, Priya Prakash -- Kotamraju, Venkata Ramana -- Agemy, Lilach -- Greenwald, Daniel R -- Ruoslahti, Erkki -- CA104898/CA/NCI NIH HHS/ -- CA115410/CA/NCI NIH HHS/ -- CA119335/CA/NCI NIH HHS/ -- CA119414/CA/NCI NIH HHS/ -- CA124427/CA/NCI NIH HHS/ -- CA30199/CA/NCI NIH HHS/ -- P01 CA104898/CA/NCI NIH HHS/ -- P01 CA104898-050002/CA/NCI NIH HHS/ -- P30 CA030199/CA/NCI NIH HHS/ -- P30 CA030199-19/CA/NCI NIH HHS/ -- R01 CA115410/CA/NCI NIH HHS/ -- R01 CA115410-04/CA/NCI NIH HHS/ -- R01 CA119414/CA/NCI NIH HHS/ -- R01 CA119414-05/CA/NCI NIH HHS/ -- R01 CA124427/CA/NCI NIH HHS/ -- R01 CA124427-04/CA/NCI NIH HHS/ -- U54 CA119335-04/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2010 May 21;328(5981):1031-5. doi: 10.1126/science.1183057. Epub 2010 Apr 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vascular Mapping Laboratory, Center for Nanomedicine, Sanford-Burnham Medical Research Institute at University of California at Santa Barbara, Biology II Building, University of California, Santa Barbara, CA 93106-9610, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20378772" target="_blank"〉PubMed〈/a〉
Keywords:
Albumin-Bound Paclitaxel
;
Albumins/administration & dosage/pharmacokinetics/therapeutic use
;
Animals
;
Antibodies, Monoclonal/administration & dosage/pharmacokinetics/therapeutic use
;
Antibodies, Monoclonal, Humanized
;
Antineoplastic Agents/*administration & dosage/pharmacokinetics/therapeutic use
;
Antineoplastic Combined Chemotherapy Protocols/*administration &
;
dosage/pharmacokinetics/therapeutic use
;
Capillary Permeability/drug effects
;
Doxorubicin/administration & dosage/pharmacokinetics/therapeutic use
;
Humans
;
Liposomes
;
Mice
;
Neoplasms/blood supply/*drug therapy/metabolism
;
Neuropilin-1/metabolism
;
Oligopeptides/*administration & dosage/metabolism/pharmacokinetics/pharmacology
;
Paclitaxel/administration & dosage/pharmacokinetics/therapeutic use
;
Permeability
;
Trastuzumab
;
Xenograft Model Antitumor Assays
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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