Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance
In order to understand the role of plasma proteins in the rapid liver clearance of dextran-coated superparamagnetic iron oxide (SPIO) in vivo, we analyzed the full repertoire of SPIO-binding blood proteins using novel two-dimensional differential mass spectrometry approach. The identified proteins s...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2012
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| Online Access: | http://hdl.handle.net/1721.1/75311 https://orcid.org/0000-0002-1293-2097 |
| _version_ | 1826208158000873472 |
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| author | Simberg, Dmitri Park, Ji-Ho Karmali, Priya P. Zhang, Wan-Ming Merkulov, Sergei McCrae, Keith Bhatia, Sangeeta N. Sailor, Michael Ruoslahti, Erkki |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Simberg, Dmitri Park, Ji-Ho Karmali, Priya P. Zhang, Wan-Ming Merkulov, Sergei McCrae, Keith Bhatia, Sangeeta N. Sailor, Michael Ruoslahti, Erkki |
| author_sort | Simberg, Dmitri |
| collection | MIT |
| description | In order to understand the role of plasma proteins in the rapid liver clearance of dextran-coated superparamagnetic iron oxide (SPIO) in vivo, we analyzed the full repertoire of SPIO-binding blood proteins using novel two-dimensional differential mass spectrometry approach. The identified proteins showed specificity for surface domains of the nanoparticles: mannan-binding lectins bound to the dextran coating, histidine-rich glycoprotein and kininogen bound to the iron oxide part, and the complement lectin and contact clotting factors were secondary binders. Nanoparticle clearance studies in knockout mice suggested that these proteins, as well as several previously identified opsonins, do not play a significant role in the SPIO clearance. However, both the dextran coat and the iron oxide core remained accessible to specific probes after incubation of SPIO in plasma, suggesting that the nanoparticle surface could be available for recognition by macrophages, regardless of protein coating. These data provide guidance to rational design of bioinert, long-circulating nanoparticles. |
| first_indexed | 2024-09-23T14:01:26Z |
| format | Article |
| id | mit-1721.1/75311 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:01:26Z |
| publishDate | 2012 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/753112022-10-01T18:36:26Z Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance Simberg, Dmitri Park, Ji-Ho Karmali, Priya P. Zhang, Wan-Ming Merkulov, Sergei McCrae, Keith Bhatia, Sangeeta N. Sailor, Michael Ruoslahti, Erkki Harvard University--MIT Division of Health Sciences and Technology Bhatia, Sangeeta N. In order to understand the role of plasma proteins in the rapid liver clearance of dextran-coated superparamagnetic iron oxide (SPIO) in vivo, we analyzed the full repertoire of SPIO-binding blood proteins using novel two-dimensional differential mass spectrometry approach. The identified proteins showed specificity for surface domains of the nanoparticles: mannan-binding lectins bound to the dextran coating, histidine-rich glycoprotein and kininogen bound to the iron oxide part, and the complement lectin and contact clotting factors were secondary binders. Nanoparticle clearance studies in knockout mice suggested that these proteins, as well as several previously identified opsonins, do not play a significant role in the SPIO clearance. However, both the dextran coat and the iron oxide core remained accessible to specific probes after incubation of SPIO in plasma, suggesting that the nanoparticle surface could be available for recognition by macrophages, regardless of protein coating. These data provide guidance to rational design of bioinert, long-circulating nanoparticles. National Cancer Institute (U.S.) (Grant CA119335) National Cancer Institute (U.S.) (Grant CA124427) 2012-12-10T15:01:11Z 2012-12-10T15:01:11Z 2009-04 2009-01 Article http://purl.org/eprint/type/JournalArticle 0142-9612 1878-5905 http://hdl.handle.net/1721.1/75311 Simberg, Dmitri et al. “Differential Proteomics Analysis of the Surface Heterogeneity of Dextran Iron Oxide Nanoparticles and the Implications for Their in Vivo Clearance.” Biomaterials 30.23-24 (2009): 3926–3933. https://orcid.org/0000-0002-1293-2097 en_US http://dx.doi.org/10.1016/j.biomaterials.2009.03.056 Biomaterials Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Elsevier PMC |
| spellingShingle | Simberg, Dmitri Park, Ji-Ho Karmali, Priya P. Zhang, Wan-Ming Merkulov, Sergei McCrae, Keith Bhatia, Sangeeta N. Sailor, Michael Ruoslahti, Erkki Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance |
| title | Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance |
| title_full | Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance |
| title_fullStr | Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance |
| title_full_unstemmed | Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance |
| title_short | Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance |
| title_sort | differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance |
| url | http://hdl.handle.net/1721.1/75311 https://orcid.org/0000-0002-1293-2097 |
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