TY - JOUR

T1 - Effect of apoA-I PEGylation on the Biological Fate of Biomimetic High-Density Lipoproteins

AU - Pedersbæk, Dennis

AU - Krogager, Louise

AU - Gregersen, Camilla Hald

AU - Ringgaard, Lars

AU - Hansen, Anders E

AU - Jønsson, Katrine

AU - Larsen, Jannik B

AU - Kjær, Andreas

AU - Andresen, Thomas L

AU - Simonsen, Jens B

N1 - © 2020 The Authors. Published by American Chemical Society.

PY - 2021

Y1 - 2021

N2 - Biomimetic high-density lipoproteins (b-HDL) have in the past two decades been applied for various drug delivery applications. As b-HDL inherently have relatively long circulation half-life and high tumor accumulation, this has inspired researchers to use b-HDL to selectively deliver drugs to tumors. PEGylation of the b-HDL has been pursued to increase the circulation half-life and therapeutic efficacy even further. The b-HDL consist of lipids stabilized by a protein/peptide scaffold, and while PEGylation of the scaffold has been shown to greatly increase the circulation half-life of the scaffold, the effect of PEGylation of the lipids is much less significant. Still, it remains to be evaluated how the biological fate, including cellular uptake, biodistribution, and circulation half-life, of the b-HDL lipids is affected by PEGylation of the b-HDL scaffold. We studied this with apolipoprotein A-I (apoA-I)-based b-HDL and mono-PEGylated b-HDL (PEG b-HDL) both in vitro and in vivo. We found that PEGylation of the b-HDL scaffold only seemed to have minimal effect on the biological fate of the lipids. Both b-HDL and PEG b-HDL overall shared similar biological fates, which includes cellular uptake through the scavenger receptor class B type 1 (SR-BI) and relatively high tumor accumulation. This highlights that b-HDL are dynamic particles, and the biological fates of the b-HDL components (lipids and scaffold) can differ. A phenomenon that may also apply for other multicomponent nanoparticles.

AB - Biomimetic high-density lipoproteins (b-HDL) have in the past two decades been applied for various drug delivery applications. As b-HDL inherently have relatively long circulation half-life and high tumor accumulation, this has inspired researchers to use b-HDL to selectively deliver drugs to tumors. PEGylation of the b-HDL has been pursued to increase the circulation half-life and therapeutic efficacy even further. The b-HDL consist of lipids stabilized by a protein/peptide scaffold, and while PEGylation of the scaffold has been shown to greatly increase the circulation half-life of the scaffold, the effect of PEGylation of the lipids is much less significant. Still, it remains to be evaluated how the biological fate, including cellular uptake, biodistribution, and circulation half-life, of the b-HDL lipids is affected by PEGylation of the b-HDL scaffold. We studied this with apolipoprotein A-I (apoA-I)-based b-HDL and mono-PEGylated b-HDL (PEG b-HDL) both in vitro and in vivo. We found that PEGylation of the b-HDL scaffold only seemed to have minimal effect on the biological fate of the lipids. Both b-HDL and PEG b-HDL overall shared similar biological fates, which includes cellular uptake through the scavenger receptor class B type 1 (SR-BI) and relatively high tumor accumulation. This highlights that b-HDL are dynamic particles, and the biological fates of the b-HDL components (lipids and scaffold) can differ. A phenomenon that may also apply for other multicomponent nanoparticles.

U2 - 10.1021/acsomega.0c05468

DO - 10.1021/acsomega.0c05468

M3 - Journal article

C2 - 33458538

VL - 6

SP - 871

EP - 880

JO - ACS Omega

JF - ACS Omega

SN - 2470-1343

IS - 1

ER -