Nuclear delivery of macromolecules: barriers and carriers

Adv Drug Deliv Rev. 2005 Feb 28;57(4):505-27. doi: 10.1016/j.addr.2004.10.004. Epub 2004 Dec 28.


Recent evidence for efficient delivery of macromolecules, such as peptides and nucleic acids, from the cell exterior to the nucleus offers the interesting possibility of developing novel treatments directed at intranuclear targets. The findings should also stimulate the search for physiological ligands that utilize similar transport mechanisms to regulate pathobiological processes. Cytokines, growth factors and their receptors, as well as morphogens have all been shown to enter the nucleus to evoke biological responses in target cells. The rational design of intracellular drug delivery vehicles requires an increased understanding of the elaborate systems that mediate cellular communication and coordination with the extracellular environment without inflicting on the integrity of the cell. This review discusses some aspects of the carriers and barriers in macromolecular transport.

Publication types

  • Review

MeSH terms

  • Biological Transport / physiology
  • Cell Membrane / drug effects*
  • Cell Membrane / physiology
  • Cell Membrane Permeability
  • Clathrin / physiology*
  • Endocytosis / drug effects
  • Endocytosis / physiology*
  • Macromolecular Substances / metabolism*
  • Nuclear Envelope / metabolism
  • Nuclear Envelope / physiology*
  • Nuclear Matrix / physiology*
  • Phagocytosis / physiology
  • Proteoglycans / metabolism
  • Proteoglycans / physiology*


  • Clathrin
  • Macromolecular Substances
  • Proteoglycans