E-selectin targeted immunoliposomes for rapamycin delivery to activated endothelial cells

Shima Gholizadeh, Ganesh Ram R. Visweswaran, Gert Storm, Wim E. Hennink, Jan A. A. M. Kamps, Robbert J. Kok*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)
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Abstract

Activated endothelial cells play a pivotal role in the pathology of inflammatory disorders and thus present a target for therapeutic intervention by drugs that intervene in inflammatory signaling cascades, such as rapamycin (mammalian target of rapamycin (mTOR) inhibitor). In this study we developed anti-E-selectin immunoliposomes for targeted delivery to E-selectin over-expressing tumor necrosis factor-alpha (TNF-alpha) activated endothelial cells. Liposomes composed of 1,2-dipalmitoyl-sn-glycero-3.; hosphocholine (DPPC), Cholesterol, and 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]-maleimide (DSPE-PEG- Mal) were loaded with rapamycin via lipid film hydration, after which they were further functionalized by coupling N-succinimidyl-S-acetylthioacetate (SATA)-modified mouse anti human E-selectin antibodies to the distal ends of the maleimidyl (Mal)-PEG groups. In cell binding assays, these immunoliposomes bound specifically to TNF-alpha activated endothelial cells. Upon internalization, rapamycin loaded immunoliposomes inhibited proliferation and migration of endothelial cells, as well as expression of inflammatory mediators. Our findings demonstrate that rapamycin-loaded immunoliposomes can specifically inhibit inflammatory responses in inflamed endothelial cells.

Original languageEnglish
Pages (from-to)759-770
Number of pages12
JournalInternational Journal of Pharmaceutics
Volume548
Issue number2
DOIs
Publication statusPublished - 15-Sep-2018
Event10th European Workshop on Particulate Systems (EWPS) - Copenhagen, Denmark
Duration: 19-Jan-201720-Jan-2017

Keywords

  • Immunoliposomes
  • Rapamycin
  • Targeted delivery
  • Endothelial cells
  • PROTEIN-KINASE B
  • MAMMALIAN TARGET
  • TNF-ALPHA
  • EXPERIMENTAL ARTHRITIS
  • RHEUMATOID-ARTHRITIS
  • ACTIN CYTOSKELETON
  • LIPID-BILAYERS
  • CANCER-THERAPY
  • IN-VITRO
  • MTOR

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