Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors
Harvard University · Massachusetts General Hospital · +1 more institution
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…
Citation impact
- FWCI
- 12.42
- Percentile
- 100%
- References
- 55
Authors
5- BDBenjamin Diop-Frimpong
Harvard University, Massachusetts General Hospital, Massachusetts Institute of Technology
- VPVikash P. Chauhan
Harvard University, Massachusetts General Hospital
- SMStephen M. Krane
Harvard University, Massachusetts General Hospital
- YBYves Boucher
Harvard University, Massachusetts General Hospital
- RKRakesh K. JainCorresponding
Harvard University, Massachusetts General Hospital
Topics & keywords
- Losartan
- Nanomedicine
- Cancer research
- Pharmacology
- Doxorubicin
- Stromal cell
- Angiotensin II
- Distribution (mathematics)
- Good health and well-being