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Region Hovedstaden - en del af Københavns Universitetshospital
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Effect of apoA-I PEGylation on the Biological Fate of Biomimetic High-Density Lipoproteins

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  • Dennis Pedersbæk
  • Louise Krogager
  • Camilla Hald Albertsen
  • Lars Ringgaard
  • Anders E Hansen
  • Katrine Jønsson
  • Jannik B Larsen
  • Andreas Kjær
  • Thomas L Andresen
  • Jens B Simonsen
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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.

OriginalsprogEngelsk
TidsskriftACS omega
Vol/bind6
Udgave nummer1
Sider (fra-til)871-880
Antal sider10
ISSN2470-1343
DOI
StatusUdgivet - 12 jan. 2021

Bibliografisk note

© 2020 The Authors. Published by American Chemical Society.

ID: 62427812