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...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
National Academy of Sciences (U.S.),
2011-09-23T18:46:47Z.
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| Subjects: | |
| Online Access: | Get fulltext |
| Summary: | 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. National Cancer Institute (U.S.) (P01CA80124) National Cancer Institute (U.S.) (R01CA85140) National Cancer Institute (U.S.) (R01CA98706) United States. Dept. of Defense (fellowship W91ZSQ7342N607) United States. Dept. of Defense (innovator award W91ZSQ7342N607) |
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