Cell-penetrating peptides in protein mimicry and cancer therapeutics
AbstractExtensive research has been undertaken in the pursuit of anticancer therapeutics. Many anticancer drugs require specificity of delivery to cancer cells, whilst sparing healthy tissue. Cell-penetrating peptides (CPPs), now well established as facilitators of intracellular delivery, have in recent years advanced to incorporate target specificity and thus possess great potential for the targeted delivery of anticancer cargoes. Though none have yet been approved for clinical use, this novel technology has already entered clinical trials. In this review we present CPPs, discuss their classification, mechanisms of cargo internalization and highlight strategies for conjugation to anticancer moieties including their incorporation into therapeutic proteins. As the mainstay of this review, strategies to build specificity into tumor targeting CPP constructs through exploitation of the tumor microenvironment and the use of tumor homing peptides are discussed, whilst acknowledging the extensive contribution made by CPP constructs to target specific protein-protein interactions integral to intracellular signaling pathways associated with tumor cell survival and progression. Finally, antibody/antigen CPP conjugates and their potential roles in cancer immunotherapy and diagnostics are considered. In summary, this review aims to harness the potential of CPP-aided drug delivery for future cancer therapies and diagnostics whilst highlighting some of the most recent achievements in selective delivery of anticancer drugs, including cytostatic drugs, to a range of tumor cells both in vitro and in vivo.
CitationZorko, M., Jones, S. and Langel, U. (2022) Cell-penetrating peptides in protein mimicry and cancer therapeutics. Advanced Drug Delivery Reviews, 180, 114044.
JournalAdvanced Drug Delivery Reviews
PubMed ID34774552 (pubmed)
Description© 2021 The Authors. Published by Elsevier. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.addr.2021.114044
SponsorsThis research was funded by the Swedish Research Council, Estonian Ministry of Education and Research (IUT20-26) and by the EU (2014–2020.4.01.15–0013).
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/
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