期刊
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
卷 129, 期 -, 页码 184-190出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2018.05.034
关键词
Nanomedicine; Non-viral gene therapy; Cationic polymers; Endosomal escape; Proton sponge hypothesis
资金
- Agency for Innovation by Science and Technology in Belgium
- Ghent University Special Research Fund
- Fund for Scientific Research Flanders (FWO, Belgium)
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program [648214]
In non-viral gene therapy, cationic polymers and lipids are frequently used to encapsulate macromolecular therapeutics into nanoparticles. During their journey to deliver the cargo to the intended intracellular target, many biological barriers need to be overcome. One of the major bottlenecks for efficient transfection is the endosomal barrier since nanoparticles often remain entrapped inside endosomes and are trafficked towards the lysosomes where the cargo is degraded. For cationic polymers, the proton sponge hypothesis was introduced in the late '90s as a way to explain their endosomal escape properties. However, to date, no consensus has been reached in the scientific community about the validity of this hypothesis due to many contradictory reports. Here we review the sometimes conflicting reports that have been published on the proton sponge hypothesis. We also discuss membrane destabilization and polymer swelling as additional factors that might influence endosomal escape of polyplexes. Based on the key publications on this subject, we aim to launch a consensus on the role of the proton sponge hypothesis in endosomal escape.
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