期刊
MOLECULES
卷 20, 期 7, 页码 13313-13323出版社
MDPI
DOI: 10.3390/molecules200713313
关键词
cell-penetrating peptides; cellular uptake; endocytosis; drug delivery; in vivo dose; drug delivery; pharmaceutical development
资金
- Research Council of Norway NANO2021 project [228200]
- Centre of Excellence funding scheme [179571]
- South Eastern Norway Regional Health Authority
- Norwegian Cancer Society
In this review, we discuss how cell-penetrating peptides (CPPs) might get access to their intracellular targets. We specifically focus on the challenge of deciding whether the positively-charged CPPs are just bound to the negatively-charged cell surface and subsequently endocytosed or actually transported into the cytosol, either by direct plasma membrane penetration or after endocytosis. This discussion includes comments about pitfalls when using pharmacological inhibitors in such studies. The possibility of exploiting CPPs as carriers for the delivery of drugs of different sizes in vitro is discussed, as is the use of CPPs as carriers for therapeutic drugs or contrast agents in vivo. We conclude that in many cases, more studies are needed to demonstrate conclusively whether increased delivery of a substance attached to CPPs is due to a membrane-penetrating property or whether the increase is a consequence of just changing the charge of the substance to be delivered. Finally, the expected dose needed for the use of such conjugates in vivo is discussed, including aspects to consider in order to bring potential products into clinical use.
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