What is it about?
CPPs broadened biomedical applications and provide a means to deliver a range of biologically active molecules, such as small molecules, proteins, imaging agents, and pharmaceutical nanocarriers, across the plasma membrane with high efficacy and low toxicity. This review is focused on the versatility of CPPs and advanced approaches for siRNA delivery.
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Why is it important?
The internal cytosolic region is separated from the extracellular region by the plasma membrane, which plays a key role in maintaining osmotic balance, cellular homeostasis, and cellular uptake activities (Takeuchi & Futaki, 2016 Takeuchi T, Futaki S. (2016). Current understanding of direct translocation of arginine-rich cell-penetrating peptides and its internalization mechanisms. Chem Pharm Bull 64:1431–7. [Crossref], [PubMed], [Web of Science ®], , [Google Scholar] ). The cytoplasmic membrane acts as a hydrophobic, defensive barrier that hampers the influx of many drugs, nucleic acids, peptides, and proteins into cells (Sawant & Torchilin, 2010 Sawant R, Torchilin V. (2010). Intracellular transduction using cell-penetrating peptides. Mol BioSyst 6:628–40. [Crossref], [PubMed], [Web of Science ®], , [Google Scholar] ). Only a few molecules possessing natural penetrating character and appropriate size, charge, and polarity are capable of directly passing through the membrane into the cytoplasm (Sawant & Torchilin, 2010 Sawant R, Torchilin V. (2010). Intracellular transduction using cell-penetrating peptides. Mol BioSyst 6:628–40. [Crossref], [PubMed], [Web of Science ®], , [Google Scholar] ). The cell membrane limits the permeability as well as the efficacy of macromolecules (e.g., nucleic acids) with high molecular weights
Perspectives
Since the discovery of CPPs and their ability to cross the cell membrane, they have been used for delivery of diverse biomolecules. Many CPP-mediated methods have been introduced due to the requirement for development of safe and effective carriers for drug delivery. In this review, we described how CPPs are biologically safe, have great promise, and are paving the way for improved drug delivery. In particular, some recent siRNA delivery approaches were summarized here. From previous studies, it has been demonstrated that conjugation of siRNA with most of the unmodified CPPs could not attain a desirable effect due to either lack of serum stability, endosomal entrapment, or some other factor. To overcome these obstacles, chemical modifications of the CPPs and/or siRNAs were performed, which enhanced the transfection efficiency. Compared to conventional methods, CPP-mediated delivery methods have more compelling advantages in terms of efficiency, siRNA-carrying capacity, and biocompatibility. However, an understanding of the CPP internalization pathway is complicated and not fully understood. Therefore, dissecting the mechanism of CPP cellular uptake will help to develop other novel CPPs with enhanced delivery and cell penetration capabilities. The arrival of CPPs is providing new opportunities for systemic siRNA delivery.
TEJINDER SINGH
Soonchunhyang University
Read the Original
This page is a summary of: Versatility of cell-penetrating peptides for intracellular delivery of siRNA, Drug Delivery, January 2018, Taylor & Francis,
DOI: 10.1080/10717544.2018.1543366.
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