Cited by 1,561RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryCellular transport and secretion

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Endosomal escape pathways for delivery of biologicals

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Varkouhi, Amir K., Scholte, Marije, Storm, Gert, Haisma, Hidde J.·2011·Journal of Controlled Release

DOI 10.1016/j.jconrel.2010.11.004

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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.

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Authors: Varkouhi, A. K., Scholte, M., Storm, G., & Haisma, H. J.
Affiliations: Utrecht University (NL)
University of Groningen (NL)
Corresponding author: Haisma, Hidde J.
ORCID: Varkouhi, Amir K.
Storm, Gert
Haisma, Hidde J.
Venue: Journal of Controlled Release
Publisher: Elsevier BV
Published: 2011-05
Volume: 151
Issue: 3
Pages: 220-228
ISSN: 0168-3659 (ISSN-L)
DOI: 10.1016/j.jconrel.2010.11.004
OpenAlex: W2008028087
Cited by: 1,561
References: 151
Citations by year: 2026: 82 · 2025: 82 · 2024: 90 · 2023: 94 · 2022: 122 · 2021: 100 · 2020: 123 · 2019: 120 · 2018: 137 · 2017: 111 · 2016: 127 · 2015: 116 · 2014: 98 · 2013: 90 · 2012: 51
FWCI: 4.32
Type: journal article
Language: en
Open access: green
research.wur.nl
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Controlled Release (publishedVersion)
PubMed (publishedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
Socio-Environmental Systems Modeling (acceptedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Funders: European Commission
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords: endosomal escape, endocytosis, lysosomal degradation, protein delivery, gene delivery, siRNA delivery, viral fusion, pH buffering, biomimetic peptides, polymers, biologic therapy
MeSH terms: Animals, Cytosol, DNA, Drug Carriers, Endocytosis, Humans, Intracellular Membranes, Membrane Fusion, Models, Biological, Proteins, Endosomes, RNA, Small Interfering

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