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Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors
Open accessAbstract
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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“Increased mechanical stress can collapse blood vessels, leading to hypoxia, thereby promoting more aggressive cancer phenotypes, and reducing drug delivery89,100–105.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [100]
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Cites
Nanocarriers as an emerging platform for cancer therapy
Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., & Langer, R. (2007) · Nature Nanotechnology · doi:10.1038/nnano.2007.387 · Cited by 8,710
Recent advances with liposomes as pharmaceutical carriers
Torchilin, V. P. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1632 · Cited by 5,282
Nanoparticle therapeutics: an emerging treatment modality for cancer
Davis, M. E., Chen, Z., & Shin, D. M. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2614 · Cited by 4,233
Delivering nanomedicine to solid tumors
Jain, R. K., & Stylianopoulos, T. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.139 · Cited by 3,265
Self-citationOlive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., et al. (2009) · Science · doi:10.1126/science.1171362 · Cited by 3,170
Collagens—structure, function, and biosynthesis
Gelse, K. (2003) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2003.08.002 · Cited by 2,777
Losartan, an AT1 Antagonist, Prevents Aortic Aneurysm in a Mouse Model of Marfan Syndrome
Habashi, J. P., Judge, D. P., Holm, T. M., Cohn, R. D., Loeys, B. L., Cooper, T. K., Myers, L., Klein, E. C., Liu, G., Calvi, C., et al. (2006) · Science · doi:10.1126/science.1124287 · Cited by 1,794
Molecular mechanisms of drug resistance
Longley, D., & Johnston, P. (2005) · The Journal of Pathology · doi:10.1002/path.1706 · Cited by 1,726
Role of extracellular matrix assembly in interstitial transport in solid tumors.
Netti, P. A., Berk, D. A., Swartz, M. A., Grodzinsky, A. J., & Jain, R. K. (2000) · PubMed · Cited by 1,165
Self-citationDynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation
Brown, E. B., McKee, T. D., DiTomaso, E., Pluen, A., Seed, B., Boucher, Y., & Jain, R. K. (2003) · Nature Medicine · doi:10.1038/nm879 · Cited by 844
Self-citationAngiotensin II Blockade and Aortic-Root Dilation in Marfan's Syndrome
Brooke, B. S., Habashi, J. P., Judge, D. P., Patel, N. D., Loeys, B., & Dietz, H. C. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0706585 · Cited by 840
Cohn, R. D., van Erp, C., Habashi, J. P., Soleimani, A. A., Klein, E. C., Lisi, M. T., Gamradt, M., Rhys, C. M. A., Holm, T. M., Loeys, B., et al. (2007) · Nature Medicine · doi:10.1038/nm1536 · Cited by 672
Senzer, N. N., Kaufman, H. L., AMATRUDA, T. T., Nemunaitis, M., Reid, T. R., Daniels, G. A., Gonzalez, R. C., Glaspy, J. A., Whitman, E. D., Harrington, K. J., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.3675 · Cited by 617
Pluen, A., Boucher, Y., Ramanujan, S., McKee, T. D., Gohongi, T., di Tomaso, E., Brown, E. B., Izumi, Y., Campbell, R. B., Berk, D. A., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081626898 · Cited by 613
Self-citationHu, J. C. C., Coffin, R. S., Davis, C. J., Graham, N. J., Groves, N., GUEST, P. J., Harrington, K. J., James, N. D., Love, C., McNeish, I. A., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0759 · Cited by 571
Diffusion and Convection in Collagen Gels: Implications for Transport in the Tumor Interstitium
Ramanujan, S., Pluen, A., McKee, T. D., Brown, E. B., Boucher, Y., & Jain, R. K. (2002) · Biophysical Journal · doi:10.1016/s0006-3495(02)73933-7 · Cited by 554
Self-citationDo inhibitors of angiotensin-I-converting enzyme protect against risk of cancer?
Lever, A. F., Hole, D. J., Gillis, C. R., McCallum, I. R., McInnes, G. T., MacKinnon, P. L., Meredith, P., Murray, L. S., Reid, J. L., & Robertson, J. W. K. (1998) · The Lancet · doi:10.1016/s0140-6736(98)03228-0 · Cited by 542
Transforming growth factor-β in cancer and metastasis
Jakowlew, S. B. (2006) · Cancer and Metastasis Reviews · doi:10.1007/s10555-006-9006-2 · Cited by 529
Nemunaitis, J. J., Khuri, F. R., Ganly, I., Arseneau, J. C., Posner, M. R., Vokes, E. E., Kuhn, J. A., McCarty, T. M., Landers, S., Blackburn, A., et al. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.2.289 · Cited by 470
Angiotensin receptors: a new role in cancer?
Deshayes, F., & Nahmias, C. (2005) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2005.07.009 · Cited by 437
Schieffer, B., Wirger, A., Meybrunn, M., Seitz, S., Holtz, J., Riede, U. N., & Drexler, H. (1994) · Circulation · doi:10.1161/01.cir.89.5.2273 · Cited by 420
McKee, T. D., Grandi, P., Mok, W., Alexandrakis, G., Insin, N., Zimmer, J. P., Bawendi, M. G., Boucher, Y., Breakefield, X. O., & Jain, R. K. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2242 · Cited by 397
Self-citationLim, D., Lutucuta, S., Bachireddy, P., Youker, K. A., Evans, A. J., Entman, M. L., Roberts, R., & Marian, A. J. (2001) · Circulation · doi:10.1161/01.cir.103.6.789 · Cited by 387
Rodríguez‐Vita, J., Sánchez‐López, E., Esteban, V., Rupérez, M., Egido, J., & Ruiz‐Ortega, M. (2005) · Circulation · doi:10.1161/01.cir.0000165133.84978.e2 · Cited by 326
The renin-angiotensin system and malignancy
Ager, E. I., Neo, J. H., & Christophi, C. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn171 · Cited by 296
Wolf, G. (2006) · Kidney International · doi:10.1038/sj.ki.5001846 · Cited by 292
Extravascular diffusion in normal and neoplastic tissues.
Nugent, L. J., & Jain, R. K. (1984) · PubMed · Cited by 290
Self-citationClinical Pharmacokinetics of Losartan
Sica, D. A., Gehr, T. W. B., & Ghosh, S. S. (2005) · Clinical Pharmacokinetics · doi:10.2165/00003088-200544080-00003 · Cited by 260
Yang, F., Chung, A. C. K., Huang, X. R., & Lan, H. Y. (2009) · Hypertension · doi:10.1161/hypertensionaha.109.136531 · Cited by 258
Tumor Blood Flow-Characterization, Modifications, and Role in Hyperthermia
Jain, R. K., & Ward-Hartley, K. A. (1984) · IEEE Transactions on Sonics and Ultrasonics · doi:10.1109/t-su.1984.31536 · Cited by 225
Self-citationAngiotensin receptor antagonists: focus on losartan
Johnston, C. I. (1995) · The Lancet · doi:10.1016/s0140-6736(95)92411-6 · Cited by 212
Kim, J.-H., Lee, Y.-S., Kim, H., Huang, J.-H., Yoon, A. R., & Yun, C. (2006) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djj397 · Cited by 211
Regression of Renal Vascular and Glomerular Fibrosis
Boffa, J., Lu, Y., Placier, S., Stefański, A., Dussaule, J., & Chatziantoniou, C. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000060574.38107.3b · Cited by 188
Rhodes, D. R., Ateeq, B., Cao, Q., Tomlins, S. A., Mehra, R., Laxman, B., Sundaram, S. K., Lonigro, R. J., Helgeson, B. E., Bhojani, M. S., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900351106 · Cited by 178
Miyajima, A., Kosaka, T., Asano, T., Asano, T., Seta, K., Kawai, T., & Hayakawa, M. (2002) · PubMed · Cited by 158
Fujita, M. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh324 · Cited by 156
Matrix Metalloproteinases-1 and -8 Improve the Distribution and Efficacy of an Oncolytic Virus
Mok, W., Boucher, Y., & Jain, R. K. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-3107 · Cited by 153
Self-citationMollenhauer, J. A., Roether, I., & Kern, H. F. (1987) · Pancreas · doi:10.1097/00006676-198701000-00003 · Cited by 145
Lavoie, P., Robitaille, G., Agharazii, M., Ledbetter, S., Lebel, M., & Larivière, R. (2005) · Journal of Hypertension · doi:10.1097/01.hjh.0000182521.44440.c5 · Cited by 141
Pancreatic Cancer: Pathobiology, Treatment Options, and Drug Delivery
Li, J., Wientjes, M. G., & Au, J. L. ‐. (2010) · The AAPS Journal · doi:10.1208/s12248-010-9181-5 · Cited by 120
TGF-β in the pathogenesis and prevention of disease: a matter of aneurysmic proportions
Dietz, H. C. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42014 · Cited by 118
Arafat, H. A., Gong, Q., Chipitsyna, G. I., Rizvi, A., Saa, C. T., & Yeo, C. J. (2007) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2007.01.067 · Cited by 111
Relaxin-Expressing, Fiber Chimeric Oncolytic Adenovirus Prolongs Survival of Tumor-Bearing Mice
Ganesh, S., Edick, M. G., Idamakanti, N., Abramova, M., VanRoey, M. J., Robinson, M. J., Yun, C., & Jooss, K. U. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4260 · Cited by 96
Angiotensin-(1-7) Reduces Fibrosis in Orthotopic Breast Tumors
Cook, K. L., Metheny‐Barlow, L. J., Tallant, E. A., & Gallagher, P. E. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1136 · Cited by 92
Angiotensin inhibition and malignancies: a review
Rosenthal, T., & Gavras, I. (2009) · Journal of Human Hypertension · doi:10.1038/jhh.2009.21 · Cited by 83
Angiotensin converting enzyme inhibitors for cancer treatment?
Nielsen, D. L., Jensen, B. V., Eriksen, J., Skovsgaard, T., & Lindberg, H. (2004) · Acta Oncologica · doi:10.1080/02841860310022346 · Cited by 77
Dexamethasone reduces the interstitial fluid pressure in a human colon adenocarcinoma xenograft.
Kristjansen, P. E. G., Boucher, Y., & Jain, R. K. (1993) · PubMed · Cited by 75
Self-citationOtake, A. H., Mattar, A. L., Freitas, H., Machado, C. M. L., Nonogaki, S., Fujihara, C. K., Zatz, R., & Chammas, R. J. (2009) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-009-1136-0 · Cited by 58
Toblli, J. E., Ferder, L., Stella, I., de Cavanagh, E. M. V., Angerosa, M., & Inserra, F. (2002) · The Journal of Urology · doi:10.1016/s0022-5347(05)64519-3 · Cited by 58
Effect of angiotensin II induced hypertension on tumor blood flow and interstitial fluid pressure.
Zlotecki, R. A., Boucher, Y., Lee, I., Baxter, L. T., & Jain, R. K. (1993) · PubMed · Cited by 57
Self-citationYoshiji, H. (2009) · Oncology Reports · doi:10.3892/or_00000445 · Cited by 49
Breitbach, C. J., Reid, T. R., Burke, J., Bell, J. C., & Kirn, D. H. (2010) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2010.02.001 · Cited by 42
Chamberlain, J. S. (2007) · Nature Medicine · doi:10.1038/nm0207-125 · Cited by 26
Khalil, A., Tullus, K., Bakhiet, M., BURMAN, L. G., Jaremko, G., & Brauner, A. (2000) · The Journal of Urology · doi:10.1016/s0022-5347(05)67492-7 · Cited by 25
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Metadata
- Authors
- Diop-Frimpong, B., Chauhan, V. P., Krane, S., Boucher, Y., & Jain, R. K.
- Affiliations
- Harvard University (US)
- Corresponding author
- Jain, Rakesh K.
- 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
- 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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