A convergent uptake route for peptide- and polymer-based nucleotide delivery systems

Journal of Controlled Release : Official Journal of the Controlled Release Society
Staffan LindbergÜlo Langel

Abstract

Cell-penetrating peptides (CPPs) have been used as vehicles to deliver various cargos into cells and are promising as tools to deliver therapeutic biomolecules such as oligonucleotides both in vitro and in vivo. CPPs are positively charged and it is believed that CPPs deliver their cargo in a receptor-independent manner by interacting with the negatively charged plasma membrane and thereby inducing endocytosis. In this study we examine the mechanism of uptake of several different, well known, CPPs that form complexes with oligonucleotides. We show that these CPP:oligonucleotide complexes are negatively charged in transfection-media and their uptake is mediated by class A scavenger receptors (SCARA). These receptors are known to promiscuously bind to, and mediate uptake of poly-anionic macromolecules. Uptake of CPP:oligonucleotide complexes was abolished using pharmacological SCARA inhibitors as well as siRNA-mediated knockdown of SCARA. Additionally, uptake of CPP:oligonucleotide was significantly increased by transiently overexpressing SCARA. Furthermore, SCARA inhibitors also blocked internalization of cationic polymer:oligonucleotide complexes. Our results demonstrate that the previous held belief that CPPs act receptor inde...Continue Reading

References

Jul 26, 1996·The Journal of Biological Chemistry·D DerossiA Prochiantz
Oct 12, 2000·The Journal of Biological Chemistry·M TyagiM Giacca
Nov 27, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ikuhiko NakaseShiroh Futaki
Feb 3, 2005·The Journal of Biological Chemistry·Jean Philippe RichardLeonid V Chernomordik
Aug 22, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gino V LimmonFarhad Imani
Oct 28, 2009·The Journal of Biological Chemistry·Jacob M GumpSteven F Dowdy
Apr 7, 2011·Nature Reviews. Genetics·Mark A Kay
Jun 21, 2011·Journal of Biophysics·Fatemeh MadaniAstrid Gräslund
Oct 5, 2011·Proceedings of the National Academy of Sciences of the United States of America·Abhijit MishraGerard C L Wong
Dec 6, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kariem EzzatUlo Langel
Apr 24, 2012·Nature Methods·Yiwen ChenX Shirley Liu
Dec 4, 2012·International Journal of Pharmaceutics·Staffan LindbergUlo Langel
Apr 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Chung Hang J ChoiChad A Mirkin
May 15, 2013·FEBS Letters·Chérine Bechara, Sandrine Sagan
Aug 29, 2013·Bioconjugate Chemistry·Piret ArukuuskUlo Langel
Jun 21, 2014·Biochimica Et Biophysica Acta·Mohammed Hakim JafferaliEinar Hallberg
Nov 28, 2014·Biomolecular Concepts·Carmine Pasquale CerratoÜlo Langel

❮ Previous
Next ❯

Citations

Jan 29, 2016·International Journal of Pharmaceutics·Jakob RegbergMattias Hällbrink
Apr 17, 2016·Nucleic Acids Research·Rudolph L Juliano
May 26, 2016·International Journal of Pharmaceutics·Karidia KonatePrisca Boisguerin
May 26, 2016·Biomaterials Science·Wenzhen LiaoYong Wang
Oct 31, 2016·Advanced Drug Delivery Reviews·Taavi LehtoSamir El Andaloussi
Nov 2, 2016·Journal of Drug Targeting·Shalmali Bivalkar-MehlaAshok Chauhan
Jan 31, 2020·PloS One·Maxime GestinÜlo Langel
Nov 25, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Carmen JuksMargus Pooga
Apr 30, 2017·Journal of Nanobiotechnology·Anaïs VaissièreSébastien Deshayes
Jul 1, 2016·Tissue Barriers·Mie Kristensen, Hanne Mørck Nielsen
Dec 20, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Manuel Hawner, Christian Ducho
Feb 6, 2020·Journal of Medicinal Chemistry·Chiara BorsariMaria P Costi
Mar 7, 2020·Biochimica Et Biophysica Acta. Biomembranes·Sébastien DeshayesPrisca Boisguérin
Jun 3, 2021·Biomedicines·Prisca BoisguérinSébastien Deshayes

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antibody-Dependent Cell Cytotoxicity

Antibody-dependent cellular toxicity refers to the lysis of a target cell by a non-sensitized effector cell of the immune system as a result of antibodies binding to the target cell membrane and engaging the Fc receptors on the immune effector cells. Find the latest research on antibody-dependent cellular toxicity here.

Related Papers

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Kariem EzzatÜlo Langel
Methods in Molecular Biology
Margus Pooga, Ülo Langel
Journal of Controlled Release : Official Journal of the Controlled Release Society
Tetsuya KadonosonoShinae Kizaka-Kondoh
Methods in Molecular Medicine
Richard Brokx, J Gariépy
© 2021 Meta ULC. All rights reserved