Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner
The blood vessels of cancerous tumours are leaky and poorly organized. This can increase the interstitial fluid pressure inside tumours and reduce blood supply to them, which impairs drug delivery. Anti-angiogenic therapies—which ‘normalize’ the abnormal blood vessels in tumours by making them less...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2013
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| Online Access: | http://hdl.handle.net/1721.1/81989 https://orcid.org/0000-0003-2220-4365 |
| _version_ | 1826212565859958784 |
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| author | Chauhan, Vikash P. Stylianopoulos, Triantafyllos Chen, Ou Kamoun, Walid S. Bawendi, Moungi G. Fukumura, Dai Jain, Rakesh K. Martin, John Daniel Popovic, Zoran |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Chauhan, Vikash P. Stylianopoulos, Triantafyllos Chen, Ou Kamoun, Walid S. Bawendi, Moungi G. Fukumura, Dai Jain, Rakesh K. Martin, John Daniel Popovic, Zoran |
| author_sort | Chauhan, Vikash P. |
| collection | MIT |
| description | The blood vessels of cancerous tumours are leaky and poorly organized. This can increase the interstitial fluid pressure inside tumours and reduce blood supply to them, which impairs drug delivery. Anti-angiogenic therapies—which ‘normalize’ the abnormal blood vessels in tumours by making them less leaky—have been shown to improve the delivery and effectiveness of chemotherapeutics with low molecular weights, but it remains unclear whether normalizing tumour vessels can improve the delivery of nanomedicines. Here, we show that repairing the abnormal vessels in mammary tumours, by blocking vascular endothelial growth factor receptor-2, improves the delivery of smaller nanoparticles (diameter, 12 nm) while hindering the delivery of larger nanoparticles (diameter, 125 nm). Using a mathematical model, we show that reducing the sizes of pores in the walls of vessels through normalization decreases the interstitial fluid pressure in tumours, thus allowing small nanoparticles to enter them more rapidly. However, increased steric and hydrodynamic hindrances, also associated with smaller pores, make it more difficult for large nanoparticles to enter tumours. Our results further suggest that smaller (~12 nm) nanomedicines are ideal for cancer therapy due to their superior tumour penetration. |
| first_indexed | 2024-09-23T15:25:26Z |
| format | Article |
| id | mit-1721.1/81989 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:25:26Z |
| publishDate | 2013 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/819892021-09-10T15:09:55Z Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner Chauhan, Vikash P. Stylianopoulos, Triantafyllos Chen, Ou Kamoun, Walid S. Bawendi, Moungi G. Fukumura, Dai Jain, Rakesh K. Martin, John Daniel Popovic, Zoran Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Chemistry Martin, John Daniel Popovic, Zoran Chen, Ou Bawendi, Moungi G. The blood vessels of cancerous tumours are leaky and poorly organized. This can increase the interstitial fluid pressure inside tumours and reduce blood supply to them, which impairs drug delivery. Anti-angiogenic therapies—which ‘normalize’ the abnormal blood vessels in tumours by making them less leaky—have been shown to improve the delivery and effectiveness of chemotherapeutics with low molecular weights, but it remains unclear whether normalizing tumour vessels can improve the delivery of nanomedicines. Here, we show that repairing the abnormal vessels in mammary tumours, by blocking vascular endothelial growth factor receptor-2, improves the delivery of smaller nanoparticles (diameter, 12 nm) while hindering the delivery of larger nanoparticles (diameter, 125 nm). Using a mathematical model, we show that reducing the sizes of pores in the walls of vessels through normalization decreases the interstitial fluid pressure in tumours, thus allowing small nanoparticles to enter them more rapidly. However, increased steric and hydrodynamic hindrances, also associated with smaller pores, make it more difficult for large nanoparticles to enter tumours. Our results further suggest that smaller (~12 nm) nanomedicines are ideal for cancer therapy due to their superior tumour penetration. ImClone Systems Incorporated National Institutes of Health (U.S.) (P01-CA080124) National Institutes of Health (U.S.) (R01-CA126642) National Institutes of Health (U.S.) (R01-CA115767) National Institutes of Health (U.S.) (R01-CA096915) National Institutes of Health (U.S.) (R01-CA085140) National Institutes of Health (U.S.) (R01-CA098706) National Institutes of Health (U.S.) (T32-CA073479) United States. Dept. of Defense (Breast Cancer Research Innovator Award W81XWH-10-1-0016) 2013-11-04T20:15:36Z 2013-11-04T20:15:36Z 2012-04 2011-12 Article http://purl.org/eprint/type/JournalArticle 1748-3387 1748-3395 http://hdl.handle.net/1721.1/81989 Chauhan, Vikash P., Triantafyllos Stylianopoulos, John D. Martin, Zoran Popović, Ou Chen, Walid S. Kamoun, Moungi G. Bawendi, Dai Fukumura, and Rakesh K. Jain. “Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner.” Nature Nanotechnology 7, no. 6 (April 8, 2012): 383-388. https://orcid.org/0000-0003-2220-4365 en_US http://dx.doi.org/10.1038/nnano.2012.45 Nature Nanotechnology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Chauhan, Vikash P. Stylianopoulos, Triantafyllos Chen, Ou Kamoun, Walid S. Bawendi, Moungi G. Fukumura, Dai Jain, Rakesh K. Martin, John Daniel Popovic, Zoran Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner |
| title | Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner |
| title_full | Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner |
| title_fullStr | Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner |
| title_full_unstemmed | Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner |
| title_short | Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner |
| title_sort | normalization of tumour blood vessels improves the delivery of nanomedicines in a size dependent manner |
| url | http://hdl.handle.net/1721.1/81989 https://orcid.org/0000-0003-2220-4365 |
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