Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles
Excessive inflammation and failed resolution of the inflammatory response are underlying components of numerous conditions such as arthritis, cardiovascular disease, and cancer. Hence, therapeutics that dampen inflammation and enhance resolution are of considerable interest. In this study, we demons...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2013
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| Online Access: | http://hdl.handle.net/1721.1/83355 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0002-6910-1905 https://orcid.org/0000-0003-4255-0492 |
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| author | Farokhzad, Omid C. Gadde, Suresh Kamaly, Nazila Fredman, Gabrielle Subramanian, Manikandan Pesic, Aleksandar Cheung, Louis Fayad, Zahi A. Tabas, Ira Langer, Robert S |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Farokhzad, Omid C. Gadde, Suresh Kamaly, Nazila Fredman, Gabrielle Subramanian, Manikandan Pesic, Aleksandar Cheung, Louis Fayad, Zahi A. Tabas, Ira Langer, Robert S |
| author_sort | Farokhzad, Omid C. |
| collection | MIT |
| description | Excessive inflammation and failed resolution of the inflammatory response are underlying components of numerous conditions such as arthritis, cardiovascular disease, and cancer. Hence, therapeutics that dampen inflammation and enhance resolution are of considerable interest. In this study, we demonstrate the proresolving activity of sub–100-nm nanoparticles (NPs) containing the anti-inflammatory peptide Ac2-26, an annexin A1/lipocortin 1-mimetic peptide. These NPs were engineered using biodegradable diblock poly(lactic-co-glycolic acid)-b-polyethyleneglycol and poly(lactic-co-glycolic acid)-b-polyethyleneglycol collagen IV–targeted polymers. Using a self-limited zymosan-induced peritonitis model, we show that the Ac2-26 NPs (100 ng per mouse) were significantly more potent than Ac2-26 native peptide at limiting recruitment of polymononuclear neutrophils (56% vs. 30%) and at decreasing the resolution interval up to 4 h. Moreover, systemic administration of collagen IV targeted Ac2-26 NPs (in as low as 1 µg peptide per mouse) was shown to significantly block tissue damage in hind-limb ischemia-reperfusion injury by up to 30% in comparison with controls. Together, these findings demonstrate that Ac2-26 NPs are proresolving in vivo and raise the prospect of their use in chronic inflammatory diseases such as atherosclerosis. |
| first_indexed | 2024-09-23T11:46:27Z |
| format | Article |
| id | mit-1721.1/83355 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:46:27Z |
| publishDate | 2013 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/833552022-09-27T21:49:22Z Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles Farokhzad, Omid C. Gadde, Suresh Kamaly, Nazila Fredman, Gabrielle Subramanian, Manikandan Pesic, Aleksandar Cheung, Louis Fayad, Zahi A. Tabas, Ira Langer, Robert S Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Langer, Robert Farokhzad, Omid C. Gadde, Suresh Kamaly, Nazila Excessive inflammation and failed resolution of the inflammatory response are underlying components of numerous conditions such as arthritis, cardiovascular disease, and cancer. Hence, therapeutics that dampen inflammation and enhance resolution are of considerable interest. In this study, we demonstrate the proresolving activity of sub–100-nm nanoparticles (NPs) containing the anti-inflammatory peptide Ac2-26, an annexin A1/lipocortin 1-mimetic peptide. These NPs were engineered using biodegradable diblock poly(lactic-co-glycolic acid)-b-polyethyleneglycol and poly(lactic-co-glycolic acid)-b-polyethyleneglycol collagen IV–targeted polymers. Using a self-limited zymosan-induced peritonitis model, we show that the Ac2-26 NPs (100 ng per mouse) were significantly more potent than Ac2-26 native peptide at limiting recruitment of polymononuclear neutrophils (56% vs. 30%) and at decreasing the resolution interval up to 4 h. Moreover, systemic administration of collagen IV targeted Ac2-26 NPs (in as low as 1 µg peptide per mouse) was shown to significantly block tissue damage in hind-limb ischemia-reperfusion injury by up to 30% in comparison with controls. Together, these findings demonstrate that Ac2-26 NPs are proresolving in vivo and raise the prospect of their use in chronic inflammatory diseases such as atherosclerosis. National Heart, Lung, and Blood Institute (Program of Excellence in Nanotechnology Award Contract HHSN268201000045C) National Institutes of Health (U.S.) (Grant CA151884) Prostate Cancer Research Foundation (Award in Nanotherapeutics) 2013-12-30T15:57:44Z 2013-12-30T15:57:44Z 2013-03 2012-12 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/83355 Kamaly, N., et al. "Development and in Vivo Efficacy of Targeted Polymeric Inflammation- Resolving Nanoparticles." Proceedings of the National Academy of Sciences of the United States of America 110 16 (2013): 6506-11. https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0002-6910-1905 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1073/pnas.1303377110 Proceedings of the National Academy of Sciences 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 National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Farokhzad, Omid C. Gadde, Suresh Kamaly, Nazila Fredman, Gabrielle Subramanian, Manikandan Pesic, Aleksandar Cheung, Louis Fayad, Zahi A. Tabas, Ira Langer, Robert S Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles |
| title | Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles |
| title_full | Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles |
| title_fullStr | Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles |
| title_full_unstemmed | Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles |
| title_short | Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles |
| title_sort | development and in vivo efficacy of targeted polymeric inflammation resolving nanoparticles |
| url | http://hdl.handle.net/1721.1/83355 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0002-6910-1905 https://orcid.org/0000-0003-4255-0492 |
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