Linear and multivalent PEGylation of the tobacco mosaic virus and the effects on its biological properties

Frontiers in Virology

Virology

Reca Marian Caballero¹  Nicole F. Steinmetz²  Stephen L. Craig³  Ivonne González-Gamboa⁴ 

[1] Department of Bioengineering, University of California, San Diego, La Jolla, CA, United States;Department of Bioengineering, University of California, San Diego, La Jolla, CA, United States;Department of Nanoengineering, University of California, San Diego, La Jolla, CA, United States;Department of Radiology, University of California, San Diego, La Jolla, CA, United States;Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States;Institute for Materials Discovery and Design, University of California, San Diego, La Jolla, CA, United States;Center for Nano-Immuno Engineering, University of California, San Diego, La Jolla, CA, United States;Center for Engineering in Cancer, University of California, San Diego, La Jolla, CA, United States;Department of Chemistry, Duke University, Durham, NC, United States;Department of Nanoengineering, University of California, San Diego, La Jolla, CA, United States;

关键词: plant virus;    tobacco mosaic virus;    PEGylation;    cell uptake;    immune evasion;    protein corona;   

DOI  :  10.3389/fviro.2023.1184095

 received in 2023-03-11, accepted in 2023-05-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

Plant virus-based nanoparticles (VNPs) offer a bioinspired approach to the delivery of drugs and imaging agents. The chemical addressability, biocompatibility, and scalable manufacturability of VNPs make them a promising alternative to synthetic delivery platforms. However, VNPs, just like other proteinaceous or synthetic nanoparticles (NPs), are readily recognized and cleared by the immune system and mechanisms such as opsonization and phagocytosis. Shielding strategies, such as PEGylation, are commonly used to mitigate premature NP clearance. Here, we investigated polyethylene glycol (PEG) coatings on the tobacco mosaic virus (TMV), which was used as a model nanocarrier system. Specifically, we evaluated the effects of linear and multivalent PEG coatings at varying chain lengths on serum protein adsorption, antibody recognition, and macrophage uptake. Linear and multivalent PEGs of molecular weights 2,000 and 5,000 Da were successfully grafted onto the TMV at ≈ 20%–60% conjugation efficiencies, and the degree of cross-linking as a function of PEG valency and length was determined. PEGylation resulted in the modulation of TMV–macrophage interactions and reduced corona formation as well as antibody recognition. Linear and multivalent PEG 5,000 formulations (but not PEG 2,000 formulations) reduced α-TMV antibody recognition, whereas shorter, multivalent PEG coatings significantly reduced α-PEG recognition—this highlights an interesting interplay between the NP and the PEG itself in potential antigenicity and should be an important consideration in PEGylation strategies. This work provides insight into the PEGylation of VNPs, which may improve the possibility of their implementation in clinical applications.

【 授权许可】

Unknown   
Copyright © 2023 Caballero, González-Gamboa, Craig and Steinmetz