Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles
Mass transport of drug delivery vehicles is guided by particle properties, such as size, shape, composition, and surface chemistry, as well as biomolecules and serum proteins that adsorb to the particle surface. In an attempt to identify serum proteins influencing cellular associations and biodistri...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
SAGE Publishing
2011-01-01
|
Series: | Molecular Imaging |
Online Access: | https://doi.org/10.2310/7290.2011.00008 |
_version_ | 1826904080943939584 |
---|---|
author | Rita E. Serda Elvin Blanco Aaron Mack Susan J. Stafford Sarah Amra Qingpo Li Anne van de Ven Takemi Tanaka Vladimir P. Torchilin John E. Wiktorowicz Mauro Ferrari |
author_facet | Rita E. Serda Elvin Blanco Aaron Mack Susan J. Stafford Sarah Amra Qingpo Li Anne van de Ven Takemi Tanaka Vladimir P. Torchilin John E. Wiktorowicz Mauro Ferrari |
author_sort | Rita E. Serda |
collection | DOAJ |
description | Mass transport of drug delivery vehicles is guided by particle properties, such as size, shape, composition, and surface chemistry, as well as biomolecules and serum proteins that adsorb to the particle surface. In an attempt to identify serum proteins influencing cellular associations and biodistribution of intravascularly injected particles, we used two-dimensional gel electrophoresis and mass spectrometry to identify proteins eluted from the surface of cationic and anionic silicon microparticles. Cationic microparticles displayed a 25-fold greater abundance of Ig light variable chain, fibrinogen, and complement component 1 compared to their anionic counterparts. Anionic microparticles were found to accumulate in equal abundance in murine liver and spleen, whereas cationic microparticles showed preferential accumulation in the spleen. Immunohistochemistry supported macrophage uptake of both anionic and cationic microparticles in the liver, as well as evidence of association of cationic microparticles with hepatic endothelial cells. Furthermore, scanning electron micrographs supported cellular competition for cationic microparticles by endothelial cells and macrophages. Despite high macrophage content in the lungs and tumor, microparticle uptake by these cells was minimal, supporting differences in the repertoire of surface receptors expressed by tissue-specific macrophages. In summary, particle surface chemistry drives selective binding of serum components impacting cellular interactions and biodistribution. |
first_indexed | 2024-03-07T17:02:49Z |
format | Article |
id | doaj.art-5163b520c78d46f5887c593203ea88e0 |
institution | Directory Open Access Journal |
issn | 1536-0121 |
language | English |
last_indexed | 2025-02-17T08:05:30Z |
publishDate | 2011-01-01 |
publisher | SAGE Publishing |
record_format | Article |
series | Molecular Imaging |
spelling | doaj.art-5163b520c78d46f5887c593203ea88e02025-01-03T00:11:36ZengSAGE PublishingMolecular Imaging1536-01212011-01-011010.2310/7290.2011.0000810.2310_7290.2011.00008Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon MicroparticlesRita E. SerdaElvin BlancoAaron MackSusan J. StaffordSarah AmraQingpo LiAnne van de VenTakemi TanakaVladimir P. TorchilinJohn E. WiktorowiczMauro FerrariMass transport of drug delivery vehicles is guided by particle properties, such as size, shape, composition, and surface chemistry, as well as biomolecules and serum proteins that adsorb to the particle surface. In an attempt to identify serum proteins influencing cellular associations and biodistribution of intravascularly injected particles, we used two-dimensional gel electrophoresis and mass spectrometry to identify proteins eluted from the surface of cationic and anionic silicon microparticles. Cationic microparticles displayed a 25-fold greater abundance of Ig light variable chain, fibrinogen, and complement component 1 compared to their anionic counterparts. Anionic microparticles were found to accumulate in equal abundance in murine liver and spleen, whereas cationic microparticles showed preferential accumulation in the spleen. Immunohistochemistry supported macrophage uptake of both anionic and cationic microparticles in the liver, as well as evidence of association of cationic microparticles with hepatic endothelial cells. Furthermore, scanning electron micrographs supported cellular competition for cationic microparticles by endothelial cells and macrophages. Despite high macrophage content in the lungs and tumor, microparticle uptake by these cells was minimal, supporting differences in the repertoire of surface receptors expressed by tissue-specific macrophages. In summary, particle surface chemistry drives selective binding of serum components impacting cellular interactions and biodistribution.https://doi.org/10.2310/7290.2011.00008 |
spellingShingle | Rita E. Serda Elvin Blanco Aaron Mack Susan J. Stafford Sarah Amra Qingpo Li Anne van de Ven Takemi Tanaka Vladimir P. Torchilin John E. Wiktorowicz Mauro Ferrari Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles Molecular Imaging |
title | Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles |
title_full | Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles |
title_fullStr | Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles |
title_full_unstemmed | Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles |
title_short | Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles |
title_sort | proteomic analysis of serum opsonins impacting biodistribution and cellular association of porous silicon microparticles |
url | https://doi.org/10.2310/7290.2011.00008 |
work_keys_str_mv | AT ritaeserda proteomicanalysisofserumopsoninsimpactingbiodistributionandcellularassociationofporoussiliconmicroparticles AT elvinblanco proteomicanalysisofserumopsoninsimpactingbiodistributionandcellularassociationofporoussiliconmicroparticles AT aaronmack proteomicanalysisofserumopsoninsimpactingbiodistributionandcellularassociationofporoussiliconmicroparticles AT susanjstafford proteomicanalysisofserumopsoninsimpactingbiodistributionandcellularassociationofporoussiliconmicroparticles AT sarahamra proteomicanalysisofserumopsoninsimpactingbiodistributionandcellularassociationofporoussiliconmicroparticles AT qingpoli proteomicanalysisofserumopsoninsimpactingbiodistributionandcellularassociationofporoussiliconmicroparticles AT annevandeven proteomicanalysisofserumopsoninsimpactingbiodistributionandcellularassociationofporoussiliconmicroparticles AT takemitanaka proteomicanalysisofserumopsoninsimpactingbiodistributionandcellularassociationofporoussiliconmicroparticles AT vladimirptorchilin proteomicanalysisofserumopsoninsimpactingbiodistributionandcellularassociationofporoussiliconmicroparticles AT johnewiktorowicz proteomicanalysisofserumopsoninsimpactingbiodistributionandcellularassociationofporoussiliconmicroparticles AT mauroferrari proteomicanalysisofserumopsoninsimpactingbiodistributionandcellularassociationofporoussiliconmicroparticles |