Polymeric Nanoparticles with Neglectable Protein Corona
Open Access
- 6 April 2020
- Vol. 16 (18), e1907574
- https://doi.org/10.1002/smll.201907574
Abstract
The current understanding of nanoparticle–protein interactions indicates that they rapidly adsorb proteins upon introduction into a living organism. The formed protein corona determines thereafter identity and fate of nanoparticles in the body. The present study evaluates the protein affinity of three core‐crosslinked polymeric nanoparticles with long circulation times, differing in the hydrophilic polymer material forming the particle surface, namely poly(N‐2‐hydroxypropylmethacrylamide) (pHPMA), polysarcosine (pSar), and poly(ethylene glycol) (PEG). This includes the nanotherapeutic CPC634, which is currently in clinical phase II evaluation. To investigate possible protein corona formation, the nanoparticles are incubated in human blood plasma and separated by asymmetrical flow field‐flow fractionation (AF4). Notably, light scattering shows no detectable differences in particle size or polydispersity upon incubation with plasma for all nanoparticles, while in gel electrophoresis, minor amounts of proteins can be detected in the particle fraction. Label‐free quantitative proteomics is additionally applied to analyze and quantify the composition of the proteins. It proves that some proteins are enriched, but their concentration is significantly less than one protein per particle. Thus, most of the nanoparticles are not associated with any proteins. Therefore, this work underlines that polymeric nanoparticles can be synthesized, for which a protein corona formation does not take place.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (SFB 1066)
This publication has 73 references indexed in Scilit:
- Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surfaceNature Nanotechnology, 2013
- Physical−Chemical Aspects of Protein Corona: Relevance to in Vitro and in Vivo Biological Impacts of NanoparticlesJournal of the American Chemical Society, 2011
- Achieving Highly Effective Nonfouling Performance for Surface-Grafted Poly(HPMA) via Atom-Transfer Radical PolymerizationLangmuir, 2010
- An overview on field-flow fractionation techniques and their applications in the separation and characterization of polymersProgress in Polymer Science, 2009
- Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticlesProceedings of the National Academy of Sciences, 2007
- Clearance of Beta-2-Microglobulin and Middle Molecules in HaemodiafiltrationPublished by S. Karger AG ,2007
- Silver staining of proteins in polyacrylamide gelsNature Protocols, 2006
- Absolute Quantification of Proteins by LCMSEMolecular & Cellular Proteomics, 2006
- Effect of physicochemical modification on the biodistribution and tumor accumulation of HPMA copolymersJournal of Controlled Release, 2005
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970