Unveiling thein VivoProtein Corona of Circulating Leukocyte-like Carriers

Abstract

Understanding interactions occurring at the interface between nanoparticles and biological components is an urgent challenge in nanomedicine due to their effect on the biological fate of nanoparticles. After the systemic injection of nanoparticles, a protein corona constructed by blood components surrounds the carrier's surface and modulates its pharmacokinetics and biodistribution. Biomimicry-based approaches in nanotechnology attempt to imitate what happens in nature in order to transfer specific natural functionalities to synthetic nanoparticles. Several biomimetic formulations have been developed, showing superior in vivo features as a result of their cell-like identity. We have recently designed biomimetic liposomes, called leukosomes, which recapitulate the ability of leukocytes to target inflamed endothelium and escape clearance by the immune system. To gain insight into the properties of leukosomes, we decided to investigate their protein corona in vivo. So far, most information about the protein corona has been obtained using in vitro experiments, which have been shown to minimally reproduce in vivo phenomena. Here we directly show a time-dependent quantitative and qualitative analysis of the protein corona adsorbed in vivo on leukosomes and control liposomes. We observed that leukosomes absorb fewer proteins than liposomes, and we identified a group of proteins specifically adsorbed on leukosomes. Moreover, we hypothesize that the presence of macrophage receptors on leukosomes' surface neutralizes their protein corona-meditated uptake by immune cells. This work unveils the protein corona of a biomimetic carrier and is one of the few studies on the corona performed in vivo.

Tracing theIn VivoFate of Nanoparticles with a “Non-Self” Biological Identity

“…cellular sequestration and subsequently experience acidification in the endolysosomal compartments in scavenger ECs. These biological processes we observed here mostly occurred within the first 1 h, and this underscores the importance of resolving early phase kinetics in the in vivo setting where rapid blood clearance is frequently reported also in mammalian models3,26,36 .…”

“…Within 30 min following IV injections, FBS PC nanoparticles are rapid sequestered by scavenger ECs and acidified in the endolysosomal compartments(2). In a longer time-frame, degradation of the FBS PC occurs around 4-6 hpi in both scavenger ECs and macrophages while the former loses its integrity(3). Concurrently, macrophages are activated to an inflammatory phenotype (M1-like polarization) that secretes the cytokine Tnfa coordinating the onset of inflammation (4).…”

Effect of Surface Chemistry and Associated Protein Corona on the Long-Term Biodegradation of Iron Oxide Nanoparticles In Vivo

“…opsonins) adsorbed in the PC are recognized by macrophages, are in the correct orientation and not masked with other proteins, they should be able to bind to macrophage receptors and be uptaken. 45 Just two hours after incubation we found that while NPs@PEG were not uptaken by the macrophages, NPs@Glc were highly uptaken. This confirms the results of the in vivo biodistribution, and has to be related with the different enrichment of proteins in each PC (as the amount of adsorbed proteins is similar), although their different orientation cannot be ruled out.…”

Biohybrid Nanoparticles to Negotiate with Biological Barriers

“…This cross‐talk leads NPs to attach to specific receptors on the surface of phagocytes . Formation of protein corona has been shown to influence cell uptake, immune response, biodistribution, and fate of NPs . Protein corona could conceal the targeting moieties (such as peptides or antibodies), leading to impairment in NPs targeting capability …”