Arginine-rich cell-penetrating peptide-modified extracellular vesicles for active macropinocytosis induction and efficient intracellular delivery

Scientific Reports
Ikuhiko NakaseShiroh Futaki

Abstract

Extracellular vesicles (EVs) including exosomes have been shown to play crucial roles in cell-to-cell communication because of their ability to carry biofunctional molecules (e.g., microRNAs and enzymes). EVs also have pharmaceutical advantages and are highly anticipated to be a next-generation intracellular delivery tool. Here, we demonstrate an experimental technique that uses arginine-rich cell-penetrating peptide (CPP)-modified EVs to induce active macropinocytosis for effective cellular EV uptake. Modification of arginine-rich CPPs on the EV membrane resulted in the activation of the macropinocytosis pathway, and the number of arginine residues in the peptide sequences affected the cellular EV uptake efficiency. Consequently, the ribosome-inactivating protein saporin-encapsulated EVs modified with hexadeca-arginine (R16) peptide effectively attained anti-cancer activity.

References

Nov 22, 2001·Bioconjugate Chemistry·S FutakiY Sugiura
Mar 7, 2003·Nature·Sean D Conner, Sandra L Schmid
Nov 1, 1995·Trends in Cell Biology·J A Swanson, C Watts
Nov 27, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ikuhiko NakaseShiroh Futaki
Jan 18, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ian M KaplanSteven F Dowdy
Nov 2, 2006·Journal of Cell Science·Sestina FalconeJacopo Meldolesi
Jan 30, 2008·Current Protocols in Cell Biology·Clotilde ThéryAled Clayton
Jul 10, 2008·Nature Reviews. Molecular Cell Biology·Joel A Swanson
Apr 16, 2009·Journal of Proteome Research·Javier Conde-VancellsJuan M Falcon-Perez
Jun 6, 2009·Nature Reviews. Immunology·Clotilde ThéryElodie Segura
Aug 27, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ikuhiko NakaseShiroh Futaki
Feb 9, 2010·Biochimica Et Biophysica Acta·Tamás LetohaLászló Szilák
Jun 10, 2010·Journal of Cellular Biochemistry·Tian TianZhongdang Xiao
Apr 12, 2011·Cancer Research·Joshua L HoodSamuel A Wickline
Jun 7, 2011·Colloids and Surfaces. B, Biointerfaces·Viktoriya SokolovaBernd Giebel
Dec 6, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Susan M van DommelenRaymond M Schiffelers
Jan 3, 2012·Accounts of Chemical Research·Ikuhiko NakaseShiroh Futaki
Jul 24, 2012·Advanced Drug Delivery Reviews·Aaron TanAlexander M Seifalian
Sep 11, 2012·Biotechnology Advances·Ruenn Chai LaiSai Kiang Lim
Mar 5, 2016·Molecular Pharmaceutics·Ran PanP Chen

❮ Previous
Next ❯

Citations

Oct 5, 2019·Expert Opinion on Drug Delivery·Kimia KardaniAzam Bolhassani
May 28, 2020·Nature Reviews. Molecular Cell Biology·Killian O'BrienXandra O Breakefield
Mar 17, 2018·The AAPS Journal·Kyle I MentkowskiJennifer K Lang
Apr 11, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Arpan S DesaiAlexander N Kapustin
Mar 16, 2019·Experimental & Molecular Medicine·Daniel E MurphyPieter Vader
Jun 12, 2020·Expert Opinion on Drug Delivery·Suchada NiamsuphapChristopher B Howard
Jan 25, 2020·Beilstein Journal of Nanotechnology·Ivana Ruseska, Andreas Zimmer
Jun 3, 2020·Nature Reviews. Cardiology·Ricardo Cerqueira de AbreuLino Ferreira
Sep 15, 2020·International Journal of Nanomedicine·Ting HuyanQi Li
Aug 6, 2020·International Journal of Molecular Sciences·Ulrike ErbMichael Karremann
Jan 13, 2019·International Journal of Molecular Sciences·Claudia CampanellaStefano Fais
Dec 15, 2019·Cancers·Francesca SusaValentina Cauda
Mar 15, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Justine Habault, Jean-Luc Poyet
Oct 9, 2020·International Journal of Molecular Sciences·Dmitry KostyushevVladimir Chulanov
Aug 8, 2020·Advanced Drug Delivery Reviews·Yaping JuSarah F Hamm-Alvarez
Aug 24, 2019·Journal of Controlled Release : Official Journal of the Controlled Release Society·Noriyasu KameiMariko Takeda-Morishita
Nov 5, 2020·Cell Proliferation·Zhenzhen MoDaniel Xin Zhang
Jan 17, 2021·Biochimica Et Biophysica Acta. Proteins and Proteomics·Gyu Chan KimYan Lee
Apr 18, 2020·Biochemical and Biophysical Research Communications·Raga IshikawaKazunari Akiyoshi
Mar 11, 2020·Biomaterials·Mei Lu, Yuanyu Huang
May 7, 2021·International Journal of Nanomedicine·Yufei FengYanhong Wang
Jun 10, 2021·Journal of Tissue Engineering·Jung-Hwan LeeHae-Won Kim
Jul 27, 2021·Frontiers in Cell and Developmental Biology·Xia Yi, Xiangqi Tang
Apr 14, 2020·ACS Nano·Bhagyashree S JoshiInge S Zuhorn
Jul 20, 2019·Bioconjugate Chemistry·Ryosuke MizutaKazunari Akiyoshi
Jun 12, 2019·Accounts of Chemical Research·Olivier G de JongRaymond M Schiffelers
Aug 24, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Soon Gil JeongByeong Hee Hwang

❮ Previous
Next ❯

Methods Mentioned

BETA
transmission electron microscopy
flow cytometry
confocal microscopy
protein assay
gel filtration

Software Mentioned

GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.