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Chemical camouflage of nanospheres with a poorly reactive surface: towards development of stealth and target-specific nanocarriers
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A two-step approach is described to chemically camouflage the inert surface of model polystyrene nanospheres of 60 nm in diameter against recognition by the body's defenses. The first step was based on the strong protein adsorbing potency of polystyrene, and the second step utilized the chemical reactivity of the adsorbed proteins for conjugation with cyanuric chloride-activated methoxypoly(ethyleneglycol)5000, mPEG5000. Bovine serum albumin (BSA) and rat IgG were used as models of non-immune and immune proteins, respectively. The maximum adsorbance values for both proteins were near expectation for a close-packed monolayer. Adsorption isotherms studies and analysis of the hydrodynamic thickness of the adsorbed protein layer confirmed the close-packed side-on mode of adsorption for BSA and the end-on mode of adsorption for IgG, respectively. Nucleophiles on the adsorbed proteins were then reacted with cyanuric chloride activated mPEG5000. The average poly(ethyleneglycol) (PEG) content for a 60-nm nanospheres was found to be 13.7+/-0.4 micromol PEG/micromol BSA and 3.6+/-0.3 micromol PEG/micromol IgG. The interaction of both PEG-bearing nanospheres with the hydrophobic column material octyl-agarose indicated surface heterogeneity among the nanospheres. Only nanospheres with the most hydrophilic phenotype (approximately 70% of the total population) exhibited stealth properties after intravenous injection to rats. In contrast to the described approach, incubation of uncoated nanospheres with preformed BSA-mPEG5000 conjugates failed to produce long circulating entities. For design of splenotropic particles cyanuric chloride-activated mPEG5000 was conjugated to BSA-coated polystyrene beads of 225 nm in diameter. Despite their stealth property to hepatic Kupffer cell recognition, these nanospheres were cleared by the splenic red pulp macrophages.
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“Attaching PEG or other hydrophilic polymers to the surface of the nanoparticles can partially shield them from immune recognition [151, 152].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [151]
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Fisicaro, E., Compari, C., Duce, E., Viscardi, G., & Quagliotto, P. (2004)
Micelles: Polymeric and Lipid-Core Drug Delivery Systems
Musacchio, T., & Torchilin, V. P. (2016) · Taylor & Francis eBooks · doi:10.1081/e-ebpp-120052264
Metadata
- Authors
- Moghimi, S. M.
- Affiliations
- University of Brighton (GB)
- Corresponding author
- Moghimi, S.M
- ORCID
- Moghimi, S.M
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
- Publisher
- Elsevier BV
- Published
- 2002-06
- Volume
- 1590
- Issue
- 1-3
- Pages
- 131-139
- ISSN
- 0167-4889 (ISSN-L)
- OpenAlex
- W2032095873
- Cited by
- 103
- References
- 23
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 7 · 2012: 5
- FWCI
- 4.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (publishedVersion)
- PubMed (publishedVersion)
- University of Brighton Repository (University of Brighton) (submittedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- chemical camouflage, polystyrene nanospheres, protein adsorption, bovine serum albumin, cyanuric chloride, PEGylation, protein adsorption isotherms, octyl-agarose, Kupffer cells
- MeSH terms
- Adsorption, Animals, Cattle, Drug Carriers, Immunoglobulin G, Injections, Intravenous, Kupffer Cells, Macrophages, Male, Microscopy, Electron, Microspheres, Particle Size, Polyethylene Glycols, Polystyrenes, Serum Albumin, Bovine, Spleen, Surface Properties, Tissue Distribution, Rats, Wistar, Nanotechnology, Rats
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