Endosomal escape pathways for delivery of biologicals

Amir K. Varkouhi, Marije Scholte, Gert Storm, Hidde J. Haisma*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1288 Citations (Scopus)

Abstract

Despite continuous improvements in delivery systems, the development of methods for efficient and specific delivery of targeted therapeutic agents still remains an issue in biological treatments such as protein and gene therapy. The endocytic pathway is the major uptake mechanism of cells and any biological agents, such as DNA, siRNA and proteins. These agents become entrapped in endosomes and are degraded by specific enzymes in the lysosome. Thus, a limiting step in achieving an effective biological based therapy is to facilitate the endosomal escape and ensure cytosolic delivery of the therapeutics. Bacteria and viruses are pathogens which use different mechanisms to penetrate the membranes of their target cells and escape the endosomal pathway. Different mechanisms such as pore formation in the endosomal membrane, pH-buffering effect of protonable groups and fusion into the lipid bilayer of endosomes have been proposed to facilitate the endosomal escape. Several viral and bacterial proteins have been identified that are involved in this process. In addition, chemical agents and photochemical methods to rupture the endosomal membrane have been described. New synthetic biomimetic peptides and polymers with high efficacy in facilitating the endosomal escape, low pathogenicity and toxicity have been developed. Each strategy has different characteristics and challenges for designing the best agents and techniques to facilitate the endosomal escape are ongoing. In this review, several mechanisms and agents which are involved in endosomal escape are introduced.

Original languageEnglish
Pages (from-to)220-228
Number of pages9
JournalJournal of Controlled Release
Volume151
Issue number3
DOIs
Publication statusPublished - 10 May 2011
Externally publishedYes

Keywords

  • Cytosolic delivery
  • Endosomal escape
  • Gene
  • Protein
  • siRNA

Fingerprint

Dive into the research topics of 'Endosomal escape pathways for delivery of biologicals'. Together they form a unique fingerprint.

Cite this