The hard protein corona of stealth liposomes is sparse

Abstract

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Pay Attention to Biological Nanoparticles when Studying the Protein Corona on Nanomedicines

“…Conversely, it could also be argued that specific proteins (that is, dysopsonins) binding to PEG chains might contribute to the stealth‐like properties of PEGylated liposomes in blood . Along these lines, the amount of proteins on PEGylated liposomes, reported in terms of the protein binding value P B (gram (protein) per mol (liposome lipids)), varies surprisingly across studies; P B ranges from approximately 5 to 120 g mol −1 in vitro in mouse plasma, and even >1000 g mol −1 in vivo in humans . Hence, we cannot clearly conclude from these studies whether the long circulation time of PEGylated liposomes is a consequence of reduced or increased protein binding; or put in another way, whether PEGylated liposomes are coated with a protein corona or not.…”

“…However, this or similar assays for determination of protein concentrations do not distinguish whether the proteins in a sample are bound to the isolated liposomes, or are just co‐eluting/‐precipitating with the liposomes. Running a blank plasma sample without liposomes (control sample) can, however, be used to assess whether bio‐nanoparticle contamination is an issue. As the presence of a protein corona should give rise to an increased protein content in the isolate when liposomes are added to the plasma, the increase over the background can be used to calculate the true protein corona content.…”

“…Hopefully, this commentary will start a constructive discussion about whether improvements are needed for the quantitative assessment of protein corona. To this end, we would like to stress the importance of including proper controls to justify the true amount and the specific proteins that comprise the protein corona on the recovered nanomedicine; for example, by subjecting control plasma/serum to the same purification procedures as the nanomedicine‐containing samples . In case the protein content in such a nanomedicine‐free sample is relatively high and/or the nanomedicine concentration is low, the background protein content could account for a significant amount of the protein corona in the “apparent” nanomedicine isolate.…”

Quantitative Protein Corona Composition and Dynamics on Carbon Nanotubes in Biological Environments

“…[4,20] Consequent work has sought to mitigate corona formation by nanoparticle surface passivation with polymers such as polyethylene glycol (PEG) to abrogate protein adsorption and sterically stabilize the nanoparticle.Ofnote,PEGylation of liposomes,amodel nanoparticle for delivery,has been demonstrated to decrease protein adsorption and maintain some functionality of surface-exposed targeting moieties. [21][22][23] Yet, such strategies can display variable efficacyd epending on the underlying nanoparticle and bioenvironmental factors. [24,25] Although many studies classify protein corona composition around specific nanoparticle systems,s ignificant debate persists as to which protein and nanoparticle characteristics are most important in determining corona composition, and how different biological environments contribute to compositional and temporal corona heterogeneity.…”

Quantitative Protein Corona Composition and Dynamics on Carbon Nanotubes in Biological Environments

“…Consequent work has sought to mitigate corona formation by nanoparticle surface passivation with polymers such as polyethylene glycol (PEG) to abrogate protein adsorption and sterically stabilize the nanoparticle. Of note, PEGylation of liposomes, a model nanoparticle for delivery, has been demonstrated to decrease protein adsorption and maintain some functionality of surface‐exposed targeting moieties [21–23] . Yet, such strategies can display variable efficacy depending on the underlying nanoparticle and bioenvironmental factors [24, 25] …”