Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors
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 lo...
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| Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 7; pp. 2909 - 2914 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
National Academy of Sciences
15.02.2011
National Acad Sciences |
| Subjects | |
| Online Access | Get full text |
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| 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. |
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| AbstractList | 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. 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.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. 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. [PUBLICATION ABSTRACT] |
| Author | Jain, Rakesh K Chauhan, Vikash P Krane, Stephen Boucher, Yves Diop-Frimpong, Benjamin |
| Author_xml | – sequence: 1 fullname: Diop-Frimpong, Benjamin – sequence: 2 fullname: Chauhan, Vikash P – sequence: 3 fullname: Krane, Stephen – sequence: 4 fullname: Boucher, Yves – sequence: 5 fullname: Jain, Rakesh K |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21282607$$D View this record in MEDLINE/PubMed |
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| Snippet | The dense collagen network in tumors significantly reduces the penetration and efficacy of nanotherapeutics. We tested whether losartan--a clinically approved... The dense collagen network in tumors significantly reduces the penetration and efficacy of nanotherapeutics. We tested whether losartan—a clinically approved... The dense collagen network in tumors significantly reduces the penetration and efficacy of nanotherapeutics. We tested whether losartan - a clinically approved... |
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| SubjectTerms | Analysis of Variance angiotensin II Animals antagonists Antineoplastics Biological Sciences biopsy breast neoplasms Breast Neoplasms - drug therapy Cancer Carcinoma - drug therapy collagen Collagen - biosynthesis Collagens DNA Primers - genetics Dosage dose response Dose-Response Relationship, Drug doxorubicin Doxorubicin - administration & dosage Doxorubicin - analogs & derivatives Drug Delivery Systems - methods Drug therapy Female fibroblasts Fluorescence Recovery After Photobleaching herpes simplex Humans Immunohistochemistry Losartan - pharmacokinetics Losartan - pharmacology Medical treatment Mice Mice, SCID nanomedicine Nanoparticles Nanoscience Nanotechnology - methods Oncolytic Virotherapy - methods Pancreatic neoplasms Pancreatic Neoplasms - drug therapy patients Pharmacology Physical Sciences Polyethylene Glycols - administration & dosage Polymerase Chain Reaction Protein synthesis Proteins Receptors Simplexvirus skin neoplasms Skin Neoplasms - drug therapy Tumors Viruses |
| Title | Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors |
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