Insight into the Cellular Uptake Mechanism of a Secondary Amphipathic Cell-Penetrating Peptide for siRNA Delivery

Biochemistry ◽  
2010 ◽  
Vol 49 (16) ◽  
pp. 3393-3402 ◽  
Author(s):  
Karidia Konate ◽  
Laurence Crombez ◽  
Sébastien Deshayes ◽  
Marc Decaffmeyer ◽  
Annick Thomas ◽  
...  
Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 554 ◽  
Author(s):  
Ghavami ◽  
Shiraishi ◽  
Nielsen

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.


RSC Advances ◽  
2021 ◽  
Vol 11 (57) ◽  
pp. 36116-36124
Author(s):  
Omar Paulino da Silva Filho ◽  
Muhanad Ali ◽  
Rike Nabbefeld ◽  
Daniel Primavessy ◽  
Petra H. Bovee-Geurts ◽  
...  

Noncovalent functionalization with acylated cell-penetrating peptides achieves an efficient cellular uptake of PLGA and PEG-PLGA nanoparticles.


2020 ◽  
Vol 11 ◽  
pp. 101-123 ◽  
Author(s):  
Ivana Ruseska ◽  
Andreas Zimmer

In today’s modern era of medicine, macromolecular compounds such as proteins, peptides and nucleic acids are dethroning small molecules as leading therapeutics. Given their immense potential, they are highly sought after. However, their application is limited mostly due to their poor in vivo stability, limited cellular uptake and insufficient target specificity. Cell-penetrating peptides (CPPs) represent a major breakthrough for the transport of macromolecules. They have been shown to successfully deliver proteins, peptides, siRNAs and pDNA in different cell types. In general, CPPs are basic peptides with a positive charge at physiological pH. They are able to translocate membranes and gain entry to the cell interior. Nevertheless, the mechanism they use to enter cells still remains an unsolved piece of the puzzle. Endocytosis and direct penetration have been suggested as the two major mechanisms used for internalization, however, it is not all black and white in the nanoworld. Studies have shown that several CPPs are able to induce and shift between different uptake mechanisms depending on their concentration, cargo or the cell line used. This review will focus on the major internalization pathways CPPs exploit, their characteristics and regulation, as well as some of the factors that influence the cellular uptake mechanism.


2009 ◽  
Vol 20 (12) ◽  
pp. 2311-2316 ◽  
Author(s):  
Dongtao Ge ◽  
Dewang Wu ◽  
Zuyong Wang ◽  
Wei Shi ◽  
Ting Wu ◽  
...  

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