Tracing the In Vivo Fate of Nanoparticles with a "Non-Self" Biological Identity

TY - JOUR

T1 - Tracing the In Vivo Fate of Nanoparticles with a "Non-Self" Biological Identity

AU - Mohammad-Beigi, Hossein

AU - Scavenius, Carsten

AU - Jensen, Pia Bomholt

AU - Kjaer-Sorensen, Kasper

AU - Oxvig, Claus

AU - Boesen, Thomas

AU - Enghild, Jan Johannes

AU - Sutherland, Duncan S

AU - Hayashi, Yuya

PY - 2020/8

Y1 - 2020/8

N2 - Nanoparticles can acquire a biomolecular corona with a species-specific biological identity. However, "non-self" incompatibility of recipient biological systems is often not considered, for example, when rodents are used as a model organism for preclinical studies of biomolecule-inspired nanomedicines. Using zebrafish embryos as an emerging model for nano-bioimaging, here we unravel the in vivo fate of intravenously injected 70 nm SiO2 nanoparticles with a protein corona pre-formed from fetal bovine serum (FBS), representing a non-self biological identity. Strikingly rapid sequestration and endolysosomal acidification of nanoparticles with the pre-formed FBS corona were observed in scavenger endothelial cells within minutes after injection. This led to loss of blood vessel integrity and to inflammatory activation of macrophages over the course of several hours. As unmodified nanoparticles or the equivalent dose of FBS proteins alone failed to induce the observed pathophysiology, this signifies how the corona enriched with a differential repertoire of proteins can determine the fate of the nanoparticles in vivo. Our findings thus reveal the adverse outcome triggered by incompatible protein coronas and indicate a potential pitfall in the use of mismatched species combinations during nanomedicine development.

AB - Nanoparticles can acquire a biomolecular corona with a species-specific biological identity. However, "non-self" incompatibility of recipient biological systems is often not considered, for example, when rodents are used as a model organism for preclinical studies of biomolecule-inspired nanomedicines. Using zebrafish embryos as an emerging model for nano-bioimaging, here we unravel the in vivo fate of intravenously injected 70 nm SiO2 nanoparticles with a protein corona pre-formed from fetal bovine serum (FBS), representing a non-self biological identity. Strikingly rapid sequestration and endolysosomal acidification of nanoparticles with the pre-formed FBS corona were observed in scavenger endothelial cells within minutes after injection. This led to loss of blood vessel integrity and to inflammatory activation of macrophages over the course of several hours. As unmodified nanoparticles or the equivalent dose of FBS proteins alone failed to induce the observed pathophysiology, this signifies how the corona enriched with a differential repertoire of proteins can determine the fate of the nanoparticles in vivo. Our findings thus reveal the adverse outcome triggered by incompatible protein coronas and indicate a potential pitfall in the use of mismatched species combinations during nanomedicine development.

U2 - 10.1101/2020.03.27.012146

DO - 10.1101/2020.03.27.012146

M3 - Journal article

C2 - 32806026

SN - 1936-0851

VL - 14

SP - 10666

EP - 10679

JO - ACS Nano

JF - ACS Nano

IS - 8

ER -