Cited by 734Nanoparticle-Based Drug DeliveryCancer Cells and MetastasisCellular Mechanics and Interactions

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Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors

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Diop-Frimpong, Benjamin, Chauhan, Vikash P., Krane, Stephen, Boucher, Yves, Jain, Rakesh K.·2011·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1018892108PMC PMC3041115

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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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Authors: Diop-Frimpong, B., Chauhan, V. P., Krane, S., Boucher, Y., & Jain, R. K.
Affiliations: Harvard University (US)
Corresponding author: Jain, Rakesh K.
ORCID: Chauhan, Vikash P.
Boucher, Yves
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2011-01-31
Volume: 108
Issue: 7
Pages: 2909-2914
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1018892108
PMC: PMC3041115
OpenAlex: W2098054841
Cited by: 733
References: 54
Citations by year: 2026: 38 · 2025: 51 · 2024: 63 · 2023: 55 · 2022: 65 · 2021: 77 · 2020: 84 · 2019: 47 · 2018: 43 · 2017: 51 · 2016: 40 · 2015: 40 · 2014: 20 · 2013: 28 · 2012: 24
FWCI: 10.23
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Funders: U.S. Department of Defense (W81XWH1010016, W81XWH)
AstraZeneca
FibroGen
Astellas Pharma
National Cancer Institute (W81XWH-10-1-0016, R01 CA 85140, R01CA98706, R01CA085140, P01CA080124, R01CA098706, P01-CA-80124)
Topics: Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords: losartan, collagen I synthesis, desmoplasia, tumor stroma, nanotherapeutics, drug penetration, oncolytic herpes simplex virus, pegylated liposomal doxorubicin, cancer-associated fibroblasts, breast cancer, pancreatic cancer, skin cancer, antifibrotic agents, tumor microenvironment
MeSH terms: Analysis of Variance, Animals, Breast Neoplasms, Carcinoma, Collagen, Dose-Response Relationship, Drug, Doxorubicin, Female, Humans, Immunohistochemistry, Pancreatic Neoplasms, Polyethylene Glycols, Skin Neoplasms, Polymerase Chain Reaction, Drug Delivery Systems, Mice, SCID, DNA Primers, Simplexvirus, Losartan, Nanotechnology, Fluorescence Recovery After Photobleaching, Oncolytic Virotherapy, Mice

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Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors

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