Targeted siRNA Delivery to Diseased Microvascular Endothelial Cells-Cellular and Molecular Concepts

Piotr S. Kowalski, Niek G. J. Leus, Gerrit L. Scherphof, Marcel H. J. Ruiters, Jan A. A. M. Kamps, Grietje Molema*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

32 Citations (Scopus)

Abstract

Increased insight in the role of endothelial cells in the pathophysiology of cancer, inflammatory and cardiovascular diseases, has drawn great interest in pharmacological interventions aiming at the endothelium in diseased sites. Their location in the body makes them suitable targets for therapeutic approaches based on targeted drug delivery. Functional heterogeneity of the microvascular bed in normal organ homeostasis has been appreciated for a long time, and more recent studies have revealed heterogeneity in endothelial reactivity to inflammatory stimuli as well. Upon stimulation, each organ displays a vascular bed specific pattern of cell adhesion molecules providing challenging opportunities to deliver drugs or small RNAs to organ specific (micro) vascular endothelial subsets. In this review we introduce general concepts of endothelial heterogeneity in relation to disease state and its consequences for targeted therapeutic interventions. Furthermore, we will describe novel approaches to interfere with endothelial cell engagement in disease with a main focus on siRNA therapeutics and currently used nonviral lipid and polymer-based siRNA delivery systems. The last part of this review addresses some technical issues that are essential in proving the concept of target mRNA knock down in a vascular bed specific manner, and the further development of effective endothelial cell specific drug delivery devices. (C) 2011 IUBMB IUBMB Life, 63(8): 648-658, 2011

Original languageEnglish
Pages (from-to)648-658
Number of pages11
JournalIubmb Life
Volume63
Issue number8
DOIs
Publication statusPublished - Aug-2011

Keywords

  • drug delivery
  • siRNA
  • endothelial cells
  • liposomes
  • targeted delivery
  • intracellular release
  • nonviral delivery devices
  • NONVIRAL GENE DELIVERY
  • DRUG-DELIVERY
  • VASCULAR ENDOTHELIUM
  • INTRACELLULAR TRAFFICKING
  • PHENOTYPIC HETEROGENEITY
  • SELECTIVE DELIVERY
  • RNA-INTERFERENCE
  • CANCER-THERAPY
  • LIPOSOMES
  • DEXAMETHASONE

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