Cell-penetrating peptides: tools for intracellular delivery of therapeutics

Cell Mol Life Sci. 2005 Aug;62(16):1839-49. doi: 10.1007/s00018-005-5109-0.


The main problem of therapeutic efficiency lies in the crossing of cellular membranes. Therefore, significant effort is being made to develop agents which can cross these barriers and deliver therapeutic agents into cellular compartments. In recent years, a large amount of data on the use of peptides as delivery agents has accumulated. Several groups have published the first positive results using peptides for the delivery of therapeutic agents in relevant animal models. These peptides, called cell-penetrating peptides (CPPs), are short peptides (fewer than 30 residues) with a net positive charge and acting in a receptor- and energy-independent manner. Here, we give an extensive review of peptide-mediated delivery systems and discuss their applications, with particular focus on the mechanisms leading to cellular internalization.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcitonin / chemistry
  • Carrier Proteins / chemistry
  • Carrier Proteins / pharmacokinetics
  • Cell Membrane Permeability*
  • Cell-Penetrating Peptides
  • Drug Delivery Systems*
  • Galanin
  • Gene Products, tat / chemistry
  • Gene Products, tat / pharmacokinetics
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacokinetics
  • Peptides / chemistry*
  • Peptides / pharmacokinetics
  • Protein Structure, Tertiary
  • Protein Transport
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / pharmacokinetics
  • Viral Structural Proteins / chemistry
  • Wasp Venoms
  • tat Gene Products, Human Immunodeficiency Virus


  • Carrier Proteins
  • Cell-Penetrating Peptides
  • Gene Products, tat
  • Peptide Fragments
  • Peptides
  • Recombinant Fusion Proteins
  • Tat peptide (37-72), Human immunodeficiency virus 1
  • Viral Structural Proteins
  • Wasp Venoms
  • herpes simplex virus type 1 protein VP22
  • tat Gene Products, Human Immunodeficiency Virus
  • transportan
  • polyarginine
  • Galanin
  • Calcitonin
  • penetratin