scholarly journals Photoinduced Endosomal Escape Mechanism: A View from Photochemical Internalization Mediated by CPP-Photosensitizer Conjugates

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 36
Author(s):  
Tet Htut Soe ◽  
Kazunori Watanabe ◽  
Takashi Ohtsuki
Keyword(s):  
Structural Design ◽  
Endosomal Escape ◽  
Cell Penetrating Peptide ◽  
Escape Mechanism ◽  
Endosomal Membrane ◽  
Photochemical Internalization ◽  
Cell Penetrating ◽  
Shed Light ◽  
Membrane Destabilization ◽  
Cargo Molecule

Endosomal escape in cell-penetrating peptide (CPP)-based drug/macromolecule delivery systems is frequently insufficient. The CPP-fused molecules tend to remain trapped inside endosomes and end up being degraded rather than delivered into the cytosol. One of the methods for endosomal escape of CPP-fused molecules is photochemical internalization (PCI), which is based on the use of light and a photosensitizer and relies on photoinduced endosomal membrane destabilization to release the cargo molecule. Currently, it remains unclear how this delivery strategy behaves after photostimulation. Recent findings, including our studies using CPP-cargo-photosensitizer conjugates, have shed light on the photoinduced endosomal escape mechanism. In this review, we discuss the structural design of CPP-photosensitizer and CPP-cargo-photosensitizer conjugates, and the PCI mechanism underlying their application.

gH625 Cell-Penetrating Peptide Promotes the Endosomal Escape of Nanovectorized siRNA in a Triple-Negative Breast Cancer Cell Line

2019 ◽  
Vol 20 (8) ◽  
pp. 3076-3086 ◽  
Author(s):  
Sanaa Ben Djemaa ◽  
Katel Hervé-Aubert ◽  
Laurie Lajoie ◽  
Annarita Falanga ◽  
Stefania Galdiero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cell Line ◽  
Triple Negative ◽  
Cancer Cell Line ◽  
Endosomal Escape ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating

scholarly journals Efficient intracellular delivery of proteins by a multifunctional chimaeric peptide in vitro and in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Siyuan Yu ◽  
Han Yang ◽  
Tingdong Li ◽  
Haifeng Pan ◽  
Shuling Ren ◽  
...  
Keyword(s):  
Protein Delivery ◽  
Leucine Zipper ◽  
Endosomal Escape ◽  
Cell Penetrating Peptide ◽  
Macromolecular Drugs ◽  
Cell Penetrating ◽  
In Series ◽  
Factor Α

AbstractProtein delivery with cell-penetrating peptide is opening up the possibility of using targets inside cells for therapeutic or biological applications; however, cell-penetrating peptide-mediated protein delivery commonly suffers from ineffective endosomal escape and low tolerance in serum, thereby limiting in vivo efficacy. Here, we present an intracellular protein delivery system consisting of four modules in series: cell-penetrating peptide, pH-dependent membrane active peptide, endosome-specific protease sites and a leucine zipper. This system exhibits enhanced delivery efficiency and serum tolerance, depending on proteolytic cleavage-facilitated endosomal escape and leucine zipper-based dimerisation. Intravenous injection of protein phosphatase 1B fused with this system successfully suppresses the tumour necrosis factor-α-induced systemic inflammatory response and acetaminophen-induced acute liver failure in a mouse model. We believe that the strategy of using multifunctional chimaeric peptides is valuable for the development of cell-penetrating peptide-based protein delivery systems, and facilitate the development of biological macromolecular drugs for use against intracellular targets.

scholarly journals Cooperative Cellular Uptake and Activity of Octaarginine Antisense Peptide Nucleic acid (PNA) Conjugates

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 554 ◽  
Author(s):  
Ghavami ◽  
Shiraishi ◽  
Nielsen
Keyword(s):  
Cellular Uptake ◽  
Peptide Nucleic Acid ◽  
Peptide Nucleic Acids ◽  
Endosomal Escape ◽  
Cell Penetrating Peptide ◽  
Uptake Mechanism ◽  
Common Effect ◽  
Cell Penetrating ◽  
Antisense Peptide ◽  
Endosomal Uptake

Cellular uptake and antisense activity of d-octaarginine conjugated peptide nucleic acids (PNAs) is shown to exhibit pronounced cooperativity in serum-containing medium, in particular by being enhanced by analogous mis-match PNA–cell-penetrating peptide (PNA–CPP) conjugates without inherent antisense activity. This cooperativity does not show cell or PNA sequence dependency, suggesting that it is a common effect in cationic CPP conjugated PNA delivery. Interestingly, our results also indicate that Deca-r8-PNA and r8-PNA could assist each other and even other non-CPP PNAs as an uptake enhancer agent. However, the peptide itself (without being attached to the PNA) failed to enhance uptake and antisense activity. These results are compatible with an endosomal uptake mechanism in which the endocytosis event is induced by multiple CPP–PNA binding to the cell surface requiring a certain CPP density, possibly in terms of nanoparticle number and/or size, to be triggered. In particular the finding that the number of endosomal events is dependent on the total CPP–PNA concentration supports such a model. It is not possible from the present results to conclude whether endosomal escape is also cooperatively induced by CPP–PNA.

scholarly journals Early Endosomal Escape of a Cyclic Cell-Penetrating Peptide Allows Effective Cytosolic Cargo Delivery

Biochemistry ◽  
2014 ◽  
Vol 53 (24) ◽  
pp. 4034-4046 ◽  
Author(s):  
Ziqing Qian ◽  
Jonathan R. LaRochelle ◽  
Bisheng Jiang ◽  
Wenlong Lian ◽  
Ryan L. Hard ◽  
...  
Keyword(s):  
Endosomal Escape ◽  
Cell Penetrating Peptide ◽  
Cargo Delivery ◽  
Cell Penetrating

Cell-penetrating peptide secures an efficient endosomal escape of an intact cargo upon a brief photo-induction

2013 ◽  
Vol 70 (24) ◽  
pp. 4825-4839 ◽  
Author(s):  
Helin Räägel ◽  
Margot Hein ◽  
Asko Kriiska ◽  
Pille Säälik ◽  
Anders Florén ◽  
...  
Keyword(s):  
Endosomal Escape ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating

A novel chimeric cell-penetrating peptide with membrane-disruptive properties for efficient endosomal escape

2012 ◽  
Vol 163 (3) ◽  
pp. 293-303 ◽  
Author(s):  
Fabrizio Salomone ◽  
Francesco Cardarelli ◽  
Mariagrazia Di Luca ◽  
Claudia Boccardi ◽  
Riccardo Nifosì ◽  
...  
Keyword(s):  
Endosomal Escape ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating ◽  
Chimeric Cell
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