Hyaluronic Acid Coated Chitosan Nanoparticles Reduced the Immunogenicity of the Formed Protein Corona

Abdulaziz Almalik,Assim A Alfadda,Majed A Majrashi,Ali H Alhasan,Afshan Masood,Ibrahim Alradwan,Haitham Alrabiah,Nicola Tirelli,Hicham Benabdelkamel,Waleed M Alghamdi,Ibrahim O Alanazi

doi:10.1038/s41598-017-10836-7

Abdulaziz Almalik, Assim A Alfadda + Show 9 more

Open Access

https://doi.org/10.1038/s41598-017-10836-7

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Journal: Scientific Reports	Publication Date: Sep 5, 2017
Citations: 131	License type: open-access

Affiliation: King Saud University, University of Manchester

Abstract

Studying the interactions of nanoparticles (NPs) with serum proteins is necessary for the rational development of nanocarriers. Optimum surface chemistry is a key consideration to modulate the formation of the serum protein corona (PC) and the resultant immune response. We investigated the constituent of the PC formed by hyaluronic acid-coated chitosan NPs (HA-CS NPs). Non-decorated chitosan NPs (CS NPs) and alginate-coated chitosan NPs (Alg-CS NPs) were utilized as controls. Results show that HA surface modifications significantly reduced protein adsorption relative to controls. Gene Ontology analysis demonstrates that HA-CS NPs were the least immunogenic nanocarriers. Indeed, less inflammatory proteins were adsorbed onto HA-CS NPs as opposed to CS and Alg-CS NPs. Interestingly, HA-CS NPs differentially adsorbed two unique anti-inflammatory proteins (ITIH4 and AGP), which were absent from the PC of both controls. On the other hand, CS and Alg-CS NPs selectively adsorbed a proinflammatory protein (Clusterin) that was not found on the surfaces of HA-CS NPs. While further studies are needed to investigate abilities of the PCs of only ITIH4 and AGP to modulate the interaction of NPs with the host immune system, our results suggest that this proof-of-concept could potentially be utilized to reduce the immunogenicity of a wide range of nanomaterials.

Highlights

Nanomaterials prepared from polysaccharides have been extensively exploited for drug delivery, because of their natural origin, chemical functionality, biodegradability, and good biocompatibility
We report a proteomics analysis of bovine serum proteins associated to the three kinds of particles, using proteome-mapping techniques followed by Gene Ontology analysis
CS, hyaluronic acid (HA)-CS, and Alg-chitosan NPs (CS NPs) were prepared using a previously optimized methodology[8] and subsequently characterized in buffers and in serum in order to understand their interactions with biological molecules

Summary

Protein Corona

Abdulaziz Almalik[1], Hicham Benabdelkamel[2], Afshan Masood[2], Ibrahim O. CS and Alg-CS NPs selectively adsorbed a proinflammatory protein (Clusterin) that was not found on the surfaces of HA-CS NPs. While further studies are needed to investigate abilities of the PCs of only ITIH4 and AGP to modulate the interaction of NPs with the host immune system, our results suggest that this proof-of-concept could potentially be utilized to reduce the immunogenicity of a wide range of nanomaterials. When CS is the main component of the NPs (CS NPs), these systems possess a cationic surface, which significantly reduces their circulation time and bioavailability upon exposure to a biological environment[8, 9] When these NPs are decorated with anionic polysaccharides, such as hyaluronic acid (HA) or alginate (Alg), both protein adsorption and the rate of macrophage uptake decreased[10, 11]. We report a proteomics analysis of bovine serum proteins associated to the three kinds of particles, using proteome-mapping techniques followed by Gene Ontology analysis

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