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WIREs Nanomed Nanobiotechnol
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Advances in cell penetrating peptides and their functionalization of polymeric nanoplatforms for drug delivery

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Abstract Cell penetrating peptides (CPPs), known as protein translocation domains, have emerged as efficient molecular transporters to overcome biological barriers and deliver cell‐impermeable cargoes into cells. The conjugation of CPPs to polymeric nanoplatforms enhances the drug delivery efficiency thus increasing their therapeutic efficacy. However, conventional CPPs are generally lack of cell specificity and could be easily degraded in vivo. These limitations lead to the development of new CPPs with superior properties. To address the issue of cell specificity, activatable CPPs have been designed to be activated at desired site through different stimuli. On the other hand, macrocyclization has been used to constrain linear CPPs into their cyclic forms. This chemical optimization of peptides endows CPPs with enhanced stability and cell permeability. This brief review will cover recent advances in terms of different types of CPPs for enhanced cell penetration. In addition, the modification chemistry used to functionalize polymeric nanoplatforms with CPPs and their recent applications for drug delivery will also be discussed. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease
The cellular uptake mechanisms of cyclic cell penetrating peptides(Reprinted with permission from Dougherty et al. (2019). Copyright 2019 American Chemical Society)
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(a) The conjugation of cyclic R9 to the PLA nanoparticles was achieved through thiol‐maleimide addition. (b) The internalization of fluorescently labeled LRT delivered by CPP‐modified nanoparticles and unmodified nanoparticles in Caco‐2 cells. An increase in fluorescence was observed with CPP‐modified nanoparticles. Scale bar: 50 μm(Reprinted with permission from Uhl et al. (2020). Copyright 2019 Elsevier)
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(a) Schematic illustration of pH activatable nanoplatform. The change of FRET signal after release of CPT from (CPT)2‐ss‐Mal could be used to monitor the drug release process. (b) Fluorescent images of 4 T1 tumor tissue sections. FRET on (green), FRET off (blue)(Reprinted with permission from Guo et al. (2018). Copyright 2017 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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(a) Schematic illustration of the in situ self‐assembly strategy with polymer‐peptide conjugates. (b) Confocal microscopic imaging of B16F10 spheroids treated with Cy5 labeled peptide–polymer conjugates. (c) Frozen sections of B16F10 tumors after treating with Cy5 labeled peptide–polymer conjugates(Reprinted with permission from Cong et al. (2019). Copyright 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease
Nanotechnology Approaches to Biology > Cells at the Nanoscale

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