Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors
Name
Diop-Frimpong-2011-Feb-Losartan inhibits co.pdf
Size
1.15 MB
Format
Adobe PDF
Checksum (MD5)
a4e87ffd665d705ca63dc7a82725701d
Author(s)
Diop-Frimpong, Benjamin
Chauhan, Vikash P.
Krane, Stephen
Boucher, Yves
Jain, Rakesh K.
Date Issued
February 2011
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences (U.S.)
Citation
Diop-Frimpong, B. et al. “Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors.” Proceedings of the National Academy of Sciences 108 (2011): 2909-2914. ©2011 by the National Academy of Sciences.
Version
Final published version
Abstract
The dense collagen network in tumors significantly reduces the penetration and efficacy of nanotherapeutics. We tested whether losartan—a clinically approved angiotensin II receptor antagonist with noted antifibrotic activity—can enhance the penetration and efficacy of nanomedicine. We found that losartan inhibited collagen I production by carcinoma-associated fibroblasts isolated from breast cancer biopsies. Additionally, it led to a dose-dependent reduction in stromal collagen in desmoplastic models of human breast, pancreatic, and skin tumors in mice. Furthermore, losartan improved the distribution and therapeutic efficacy of intratumorally injected oncolytic herpes simplex viruses. Finally, it also enhanced the efficacy of i.v. injected pegylated liposomal doxorubicin (Doxil). Thus, losartan has the potential to enhance the efficacy of nanotherapeutics in patients with desmoplastic tumors.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1073/pnas.1018892108
