The Protein Corona Does Not Influence Receptor-Mediated Targeting of Virus-like Particles

Abstract

Protein corona formation has been regarded as an obstacle to developing diagnostic and therapeutic nanoparticles for in vivo applications. Serum proteins that assemble around nanoparticles can hinder their targeting efficiency. Virus-based nanoparticles should be naturally predisposed to evade such barriers in host organisms. Here, we demonstrate that virus-like particles derived from mouse polyomavirus do not form a rich protein corona. These particles can be efficiently targeted to cells that overproduce transferrin receptors, e.g., cancer cells, by conjugating transferrin to the particle surface. In this study, we provide evidence that the interaction of virus-like particles with their newly assigned target receptor is not obstructed by serum proteins. The particles enter target cells via a clathrin-dependent endocytic pathway that is not naturally used by the virus. Our results support the notion that the natural properties of virus-like particles make them well-suited for development of nanosized theranostic tools resistant to detargeting by protein coronas.

Enhancing Immunity with Nanomedicine: Employing Nanoparticles to Harness the Immune System

“…98 Recently, researchers identified that the ability of polyomavirus-based VLPs to engage their target receptors was not affected by the protein corona. 99 These VLPs maintained target specificity and were internalized into cancer cells via clathrin-dependent endocytosis in the presence of human serum. These findings fit with the idea that viruses have evolved mechanisms of immune avoidance that ameliorate their ability to deliver enclosed genetic material.…”

“…The findings of Alam et al are particularly interesting because VLP-based vaccine platforms may circumvent challenges associated with protein corona formation such as interfering with targeting . Recently, researchers identified that the ability of polyomavirus-based VLPs to engage their target receptors was not affected by the protein corona . These VLPs maintained target specificity and were internalized into cancer cells via clathrin-dependent endocytosis in the presence of human serum.…”

Protein nanoparticles directed cancer imaging and therapy

“…VLPs inherit the advantages of proteins and can be genetically modified with targeting peptides, whereas inorganic nanoparticles are generally modified with the targeting ligands through direct chemical coupling or through the use of organic polymer linkers [ 150 ]. In addition, studies have shown that the targeting ability of VLPs will not be adversely affected by protein corona [ 151 ]. However, when silica was modified with transferrin, the protein corona formed on the surface of silica would shield transferrin, making it lose the ability to bind with transferrin receptors.…”

Insights into Characterization Methods and Biomedical Applications of Nanoparticle–Protein Corona

“…The formation of serum PCs around NPs is generally considered to hinder the targeting efficiency of NPs. In the case of serum proteins coated with transferrin (Tf) functionalized virus-like particles, recent studies have indicated that they can successfully target cancer cells with transferrin receptors via the covalent coupling of Tf molecules on the capsid surface, i.e., the PCs have no effect on their uptake into tumor cells [133]. Tuning PCs by modulating the surface chemistry of NPs opens up great potential for the regulation of the non-specific cellular uptake of NP-PC complexes and for improving the therapeutic efficacy of nanomedicines.…”

“…successfully target cancer cells with transferrin receptors via the covalent coupling of Tf molecules on the capsid surface, i.e., the PCs have no effect on their uptake into tumor cells [133]. Tuning PCs by modulating the surface chemistry of NPs opens up great potential for the regulation of the nonspecific cellular uptake of NP-PC complexes and for improving the therapeutic efficacy of nanomedicines.…”