Transport by circulating myeloid cells drives liposomal accumulation in inflamed synovium

Joke Deprez, Rein Verbeke, Sofie Meulewaeter, Ilke Aernout, Heleen Dewitte, Tine Decruy, Julie Coudenys, Julie Van Duyse, Gert Van Isterdael, Dan Peer, Roy van der Meel, Stefaan C. De Smedt, Peggy Jacques, Dirk Elewaut, Ine Lentacker

Research output: Contribution to journalArticlepeer-review


The therapeutic potential of liposomes to deliver drugs into inflamed tissue is well documented. Liposomes are believed to largely transport drugs into inflamed joints by selective extravasation through endothelial gaps at the inflammatory sites, known as the enhanced permeation and retention effect. However, the potential of blood-circulating myeloid cells for the uptake and delivery of liposomes has been largely overlooked. Here we show that myeloid cells can transport liposomes to inflammatory sites in a collagen-induced arthritis model. It is shown that the selective depletion of the circulating myeloid cells reduces the accumulation of liposomes up to 50–60%, suggesting that myeloid-cell-mediated transport accounts for more than half of liposomal accumulation in inflamed regions. Although it is widely believed that PEGylation inhibits premature liposome clearance by the mononuclear phagocytic system, our data show that the long blood circulation times of PEGylated liposomes rather favours uptake by myeloid cells. This challenges the prevailing theory that synovial liposomal accumulation is primarily due to the enhanced permeation and retention effect and highlights the potential for other pathways of delivery in inflammatory diseases.

Original languageEnglish
Pages (from-to)1341-1350
Number of pages10
JournalNature Nanotechnology
Issue number11
StatePublished - Nov 2023

All Science Journal Classification (ASJC) codes

  • Condensed Matter Physics
  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Electrical and Electronic Engineering
  • Biomedical Engineering
  • General Materials Science


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