Cellular Internalization and Distribution of Arginine-Rich Peptides as a Function of Extracellular Peptide Concentration, Serum, and Plasma Membrane Associated ProteoglycansClick to copy article linkArticle link copied!
Abstract
The exact mechanisms by which arginine-rich cell-penetrating peptides enter cells are still the subject of debate. Here, we have analyzed in detail the effects of serum and extracellular concentration on the internalization of oligoarginines (Rn; n = 4, 8, 12, 16). The presence of serum in the incubation medium had a major influence on the uptake of R12 and R16 peptides but did not affect the uptake of R4 and R8 significantly. Incubation of cells at 37 °C with R12 and R16 peptides in serum-containing medium showed that the majority of labeling was confined to punctate endocytic structures. Performing the same experiments in serum-free media led to a dramatic increase in cytosolic labeling, and similarly diffuse R12 and R16 labeling was observed in cells treated with peptides at 4 °C. This suggests, in both cases, that the peptides were entering via a nonendocytic mechanism. Further studies on R12 peptide suggest that the initiation of nonendocytic uptake and cytosolic labeling is also dependent on serum concentration and extracellular peptide concentration. At relatively low concentrations, the peptide labels endocytic structures, but upon raising the peptide concentration, the fraction labeling the cytosol increases dramatically and this accompanies a nonlinear increase in total cellular fluorescence. Membrane-associated proteoglycans also contribute to increasing the peptide concentration at the cell surface by enhancing their recruitment via electrostatic interactions. These results demonstrate that uptake mechanisms of these compounds are highly dependent on both the presence of serum and the effective extracellular peptide concentration.
Cited By
This article is cited by 290 publications.
- Ashweta Sahni, Jeremy L. Ritchey, Ziqing Qian, Dehua Pei. Cell-Penetrating Peptides Translocate across the Plasma Membrane by Inducing Vesicle Budding and Collapse. Journal of the American Chemical Society 2024, 146
(36)
, 25371-25382. https://doi.org/10.1021/jacs.4c10533
- Machi Hata, Yuki Kadoya, Jin Ueno, Masayasu Taki, Masahito Kodera. Dicopper Complexes of p-Cresol-2,6-bis(amide-tether-dpa4-X) (X = MeO and Cl): Selective ROS Generation and Cytotoxicity Enhancement Controlled by Electronic and Hydrophobic Effects of the MeO and Cl Groups. Inorganic Chemistry 2024, 63
(30)
, 13893-13902. https://doi.org/10.1021/acs.inorgchem.4c01072
- Haruya Yagi, Takumi Tomono, Koji Abe, Yasuhiro Tsutsumi, Muneyoshi Makabe, Hiromi Mitsuhashi, Takayuki Kimura, Hideo Kobayashi, Kohei Miyata, Koichi Shigeno, Shinji Sakuma. Validation of the Absorption-Enhancing Ability of Oligoarginines Grafted onto a Backbone of Hyaluronic Acid through Animal Studies from Rodents to Primates. Molecular Pharmaceutics 2024, 21
(7)
, 3485-3501. https://doi.org/10.1021/acs.molpharmaceut.4c00184
- Jan Vincent V. Arafiles, Jonathan Franke, Luise Franz, Jacobo Gómez-González, Kristin Kemnitz-Hassanin, Christian P. R. Hackenberger. Cell-Surface-Retained Peptide Additives for the Cytosolic Delivery of Functional Proteins. Journal of the American Chemical Society 2023, 145
(45)
, 24535-24548. https://doi.org/10.1021/jacs.3c05365
- Mika Omura, Kenta Morimoto, Yurina Araki, Hisaaki Hirose, Yoshimasa Kawaguchi, Yukiya Kitayama, Yuto Goto, Atsushi Harada, Ikuo Fujii, Tomoka Takatani-Nakase, Shiroh Futaki, Ikuhiko Nakase. Inkjet-Based Intracellular Delivery System that Effectively Utilizes Cell-Penetrating Peptides for Cytosolic Introduction of Biomacromolecules through the Cell Membrane. ACS Applied Materials & Interfaces 2023, 15
(41)
, 47855-47865. https://doi.org/10.1021/acsami.3c01650
- Xiaoyu Feng, Ruilong Chang, Haichao Zhu, Yifan Yang, Yue Ji, Dingkang Liu, Hai Qin, Jun Yin, Haibo Rong. Engineering Proteins for Cell Entry. Molecular Pharmaceutics 2023, 20
(10)
, 4868-4882. https://doi.org/10.1021/acs.molpharmaceut.3c00467
- Andréanne Laniel, Étienne Marouseau, Duc Tai Nguyen, Ulrike Froehlich, Claire McCartney, Pierre-Luc Boudreault, Christine Lavoie. Characterization of PGua4, a Guanidinium-Rich Peptoid that Delivers IgGs to the Cytosol via Macropinocytosis. Molecular Pharmaceutics 2023, 20
(3)
, 1577-1590. https://doi.org/10.1021/acs.molpharmaceut.2c00783
- Haruya Yagi, Takumi Tomono, Yuma Handa, Natsuki Saito, Masami Ukawa, Kohei Miyata, Koichi Shigeno, Shinji Sakuma. Performance of Cell-Penetrating Peptides Anchored to Polysaccharide Platforms Applied via Various Mucosal Routes as an Absorption Enhancer. Molecular Pharmaceutics 2023, 20
(1)
, 303-313. https://doi.org/10.1021/acs.molpharmaceut.2c00657
- Ikuhiko Nakase, Moe Miyai, Kosuke Noguchi, Mamoru Tamura, Yasuyuki Yamamoto, Yushi Nishimura, Mika Omura, Kota Hayashi, Shiroh Futaki, Shiho Tokonami, Takuya Iida. Light-Induced Condensation of Biofunctional Molecules around Targeted Living Cells to Accelerate Cytosolic Delivery. Nano Letters 2022, 22
(24)
, 9805-9814. https://doi.org/10.1021/acs.nanolett.2c02437
- Kayo Nomura, Kenichi Kawano, Yoshimasa Kawaguchi, Yuki Kawamura, Junya Michibata, Keiko Kuwata, Koji Sugiyama, Kenji Kusumoto, Shiroh Futaki. Hemopexin as a Potential Binding Partner of Arginine-Rich Cell-Penetrating Peptides in Serum. ACS Pharmacology & Translational Science 2022, 5
(8)
, 603-615. https://doi.org/10.1021/acsptsci.2c00043
- Yuna Nakagawa, Jan Vincent V. Arafiles, Yoshimasa Kawaguchi, Ikuhiko Nakase, Hisaaki Hirose, Shiroh Futaki. Stearylated Macropinocytosis-Inducing Peptides Facilitating the Cellular Uptake of Small Extracellular Vesicles. Bioconjugate Chemistry 2022, 33
(5)
, 869-880. https://doi.org/10.1021/acs.bioconjchem.2c00113
- Thomas G. W. Edwardson, Mikail D. Levasseur, Stephan Tetter, Angela Steinauer, Mao Hori, Donald Hilvert. Protein Cages: From Fundamentals to Advanced Applications. Chemical Reviews 2022, 122
(9)
, 9145-9197. https://doi.org/10.1021/acs.chemrev.1c00877
- Kentarou Sakamoto, Hiroto Furukawa, Jan Vincent V. Arafiles, Miki Imanishi, Kazunori Matsuura, Shiroh Futaki. Artificial Nanocage Formed via Self-Assembly of β-Annulus Peptide for Delivering Biofunctional Proteins into Cell Interiors. Bioconjugate Chemistry 2022, 33
(2)
, 311-320. https://doi.org/10.1021/acs.bioconjchem.1c00534
- Yuebao Zhang, Changzhen Sun, Chang Wang, Katarina E. Jankovic, Yizhou Dong. Lipids and Lipid Derivatives for RNA Delivery. Chemical Reviews 2021, 121
(20)
, 12181-12277. https://doi.org/10.1021/acs.chemrev.1c00244
- Kosuke Noguchi, Momoko Obuki, Haruka Sumi, Merlin Klußmann, Kenta Morimoto, Shinya Nakai, Takuya Hashimoto, Daisuke Fujiwara, Ikuo Fujii, Eiji Yuba, Tomoka Takatani-Nakase, Ines Neundorf, Ikuhiko Nakase. Macropinocytosis-Inducible Extracellular Vesicles Modified with Antimicrobial Protein CAP18-Derived Cell-Penetrating Peptides for Efficient Intracellular Delivery. Molecular Pharmaceutics 2021, 18
(9)
, 3290-3301. https://doi.org/10.1021/acs.molpharmaceut.1c00244
- Xinlin Jiang, Jijun Fu, Junyang Zhong, Xin Li, He Wang, Songjing Zhong, Yinhui Wei, Xiaoya Zhao, Xing Chen, Yi Zhou, Lingran Du, Guodong Ye, Jing Zhao, Yugang Huang. Guanidinylated Cyclic Synthetic Polypeptides Can Effectively Deliver siRNA by Mimicking the Biofunctions of Both Cell-Penetrating Peptides and Nuclear Localization Signal Peptides. ACS Macro Letters 2021, 10
(7)
, 767-773. https://doi.org/10.1021/acsmacrolett.1c00236
- Kentarou Sakamoto, Junya Michibata, Yusuke Hirai, Akiko Ide, Asuka Ikitoh, Tomoka Takatani-Nakase, Shiroh Futaki. Potentiating the Membrane Interaction of an Attenuated Cationic Amphiphilic Lytic Peptide for Intracellular Protein Delivery by Anchoring with Pyrene Moiety. Bioconjugate Chemistry 2021, 32
(5)
, 950-957. https://doi.org/10.1021/acs.bioconjchem.1c00101
- Hiroki Ida, Yasufumi Takahashi, Akichika Kumatani, Hitoshi Shiku, Tomo Murayama, Hisaaki Hirose, Shiroh Futaki, Tomokazu Matsue. Nanoscale Visualization of Morphological Alteration of Live-Cell Membranes by the Interaction with Oligoarginine Cell-Penetrating Peptides. Analytical Chemistry 2021, 93
(13)
, 5383-5393. https://doi.org/10.1021/acs.analchem.0c04097
- Hiroaki Kitagishi, Misa Jiromaru, Naomi Hasegawa. Intracellular Delivery of Adamantane-Tagged Small Molecule, Proteins, and Liposomes Using an Octaarginine-Conjugated β-Cyclodextrin. ACS Applied Bio Materials 2020, 3
(8)
, 4902-4911. https://doi.org/10.1021/acsabm.0c00421
- Natalia Sánchez-Arribas, María Martínez-Negro, Eva M. Villar, Lourdes Pérez, Emilio Aicart, Pablo Taboada, Andrés Guerrero-Martínez, Elena Junquera. Biocompatible Nanovector of siRNA Consisting of Arginine-Based Cationic Lipid for Gene Knockdown in Cancer Cells. ACS Applied Materials & Interfaces 2020, 12
(31)
, 34536-34547. https://doi.org/10.1021/acsami.0c06273
- Chiara Borsari, Darci J. Trader, Annalisa Tait, Maria P. Costi. Designing Chimeric Molecules for Drug Discovery by Leveraging Chemical Biology. Journal of Medicinal Chemistry 2020, 63
(5)
, 1908-1928. https://doi.org/10.1021/acs.jmedchem.9b01456
- Colin
M. Fadzen, Rebecca L. Holden, Justin M. Wolfe, Zi-Ning Choo, Carly K. Schissel, Monica Yao, Gunnar J. Hanson, Bradley L. Pentelute. Chimeras of Cell-Penetrating Peptides Demonstrate Synergistic Improvement in Antisense Efficacy. Biochemistry 2019, 58
(38)
, 3980-3989. https://doi.org/10.1021/acs.biochem.9b00413
- Meng-Chan Xia, Lesi Cai, Yan Yang, Sichun Zhang, Xinrong Zhang. Tuning the pKa of Carboxyfluorescein with Arginine-Rich Cell-Penetrating Peptides for Intracellular pH Imaging. Analytical Chemistry 2019, 91
(14)
, 9168-9173. https://doi.org/10.1021/acs.analchem.9b01864
- Akiko Okuda, Shinya Tahara, Hisaaki Hirose, Toshihide Takeuchi, Ikuhiko Nakase, Atsushi Ono, Masanori Takehashi, Seigo Tanaka, Shiroh Futaki. Oligoarginine-Bearing Tandem Repeat Penetration-Accelerating Sequence Delivers Protein to Cytosol via Caveolae-Mediated Endocytosis. Biomacromolecules 2019, 20
(5)
, 1849-1859. https://doi.org/10.1021/acs.biomac.8b01299
- Kirsten Deprey, Lukas Becker, Joshua Kritzer, Andreas Plückthun. Trapped! A Critical Evaluation of Methods for Measuring Total Cellular Uptake versus Cytosolic Localization. Bioconjugate Chemistry 2019, 30
(4)
, 1006-1027. https://doi.org/10.1021/acs.bioconjchem.9b00112
- Yoshimasa Kawaguchi, Shoko Ise, Yusuke Azuma, Toshihide Takeuchi, Kenichi Kawano, Toan Khanh Le, Junko Ohkanda, Shiroh Futaki. Dipicolylamine/Metal Complexes that Promote Direct Cell-Membrane Penetration of Octaarginine. Bioconjugate Chemistry 2019, 30
(2)
, 454-460. https://doi.org/10.1021/acs.bioconjchem.8b00691
- Chao-Chen Lin, Michael Bachmann, Simon Bachler, Koushik Venkatesan, Petra S. Dittrich. Tunable Membrane Potential Reconstituted in Giant Vesicles Promotes Permeation of Cationic Peptides at Nanomolar Concentrations. ACS Applied Materials & Interfaces 2018, 10
(49)
, 41909-41916. https://doi.org/10.1021/acsami.8b12217
- Leila Peraro, Kirsten L. Deprey, Matthew K. Moser, Zhongju Zou, Haydn L. Ball, Beth Levine, Joshua A. Kritzer. Cell Penetration Profiling Using the Chloroalkane Penetration Assay. Journal of the American Chemical Society 2018, 140
(36)
, 11360-11369. https://doi.org/10.1021/jacs.8b06144
- Annely Lorents, Pille Säälik, Ülo Langel, Margus Pooga. Arginine-Rich Cell-Penetrating Peptides Require Nucleolin and Cholesterol-Poor Subdomains for Translocation across Membranes. Bioconjugate Chemistry 2018, 29
(4)
, 1168-1177. https://doi.org/10.1021/acs.bioconjchem.7b00805
- Kristina Najjar, Alfredo Erazo-Oliveras, John W. Mosior, Megan J. Whitlock, Ikram Rostane, Joseph M. Cinclair, and Jean-Philippe Pellois . Unlocking Endosomal Entrapment with Supercharged Arginine-Rich Peptides. Bioconjugate Chemistry 2017, 28
(12)
, 2932-2941. https://doi.org/10.1021/acs.bioconjchem.7b00560
- Shiroh Futaki and Ikuhiko Nakase . Cell-Surface Interactions on Arginine-Rich Cell-Penetrating Peptides Allow for Multiplex Modes of Internalization. Accounts of Chemical Research 2017, 50
(10)
, 2449-2456. https://doi.org/10.1021/acs.accounts.7b00221
- Ting-Yi Wang, M. Daben J. Libardo, Alfredo M. Angeles-Boza, and Jean-Philippe Pellois . Membrane Oxidation in Cell Delivery and Cell Killing Applications. ACS Chemical Biology 2017, 12
(5)
, 1170-1182. https://doi.org/10.1021/acschembio.7b00237
- Saika Minegishi, Aki Yumura, Hirotsuna Miyoshi, Shigeru Negi, Shigeru Taketani, Roberto Motterlini, Roberta Foresti, Koji Kano, and Hiroaki Kitagishi . Detection and Removal of Endogenous Carbon Monoxide by Selective and Cell-Permeable Hemoprotein Model Complexes. Journal of the American Chemical Society 2017, 139
(16)
, 5984-5991. https://doi.org/10.1021/jacs.7b02229
- Samuel Schmidt, Merel J. W. Adjobo-Hermans, Robin Kohze, Thilo Enderle, Roland Brock, and Francesca Milletti . Identification of Short Hydrophobic Cell-Penetrating Peptides for Cytosolic Peptide Delivery by Rational Design. Bioconjugate Chemistry 2017, 28
(2)
, 382-389. https://doi.org/10.1021/acs.bioconjchem.6b00535
- Yoshimasa Kawaguchi, Toshihide Takeuchi, Keiko Kuwata, Junya Chiba, Yasumaru Hatanaka, Ikuhiko Nakase, and Shiroh Futaki . Syndecan-4 Is a Receptor for Clathrin-Mediated Endocytosis of Arginine-Rich Cell-Penetrating Peptides. Bioconjugate Chemistry 2016, 27
(4)
, 1119-1130. https://doi.org/10.1021/acs.bioconjchem.6b00082
- Nobuyuki Morimoto, Masaru Wakamura, Kanna Muramatsu, Sayaka Toita, Masafumi Nakayama, Wataru Shoji, Makoto Suzuki, and Françoise M. Winnik . Membrane Translocation and Organelle-Selective Delivery Steered by Polymeric Zwitterionic Nanospheres. Biomacromolecules 2016, 17
(4)
, 1523-1535. https://doi.org/10.1021/acs.biomac.6b00172
- Wataru Nomura, Nami Ohashi, Atsumi Mori, and Hirokazu Tamamura . An In-Cell Fluorogenic Tag–Probe System for Protein Dynamics Imaging Enabled by Cell-Penetrating Peptides. Bioconjugate Chemistry 2015, 26
(6)
, 1080-1085. https://doi.org/10.1021/acs.bioconjchem.5b00131
- Yosuke Hisamatsu, Ai Shibuya, Nozomi Suzuki, Toshihiro Suzuki, Ryo Abe, and Shin Aoki . Design and Synthesis of Amphiphilic and Luminescent Tris-Cyclometalated Iridium(III) Complexes Containing Cationic Peptides as Inducers and Detectors of Cell Death via a Calcium-Dependent Pathway. Bioconjugate Chemistry 2015, 26
(5)
, 857-879. https://doi.org/10.1021/acs.bioconjchem.5b00095
- Xiaoyan Zou, Megha Rajendran, Darren Magda, and Lawrence W. Miller . Cytoplasmic Delivery and Selective, Multicomponent Labeling with Oligoarginine-Linked Protein Tags. Bioconjugate Chemistry 2015, 26
(3)
, 460-465. https://doi.org/10.1021/bc500550z
- Gerard J. Hilinski, Young-Woo Kim, Jooyeon Hong, Peter S. Kutchukian, Charisse M. Crenshaw, Shaunna S. Berkovitch, Andrew Chang, Sihyun Ham, and Gregory L. Verdine . Stitched α-Helical Peptides via Bis Ring-Closing Metathesis. Journal of the American Chemical Society 2014, 136
(35)
, 12314-12322. https://doi.org/10.1021/ja505141j
- Roland Brock . The Uptake of Arginine-Rich Cell-Penetrating Peptides: Putting the Puzzle Together. Bioconjugate Chemistry 2014, 25
(5)
, 863-868. https://doi.org/10.1021/bc500017t
- Chunmeng Sun, Wei-Chiang Shen, Jiasheng Tu, and Jennica L. Zaro . Interaction between Cell-Penetrating Peptides and Acid-Sensitive Anionic Oligopeptides as a Model for the Design of Targeted Drug Carriers. Molecular Pharmaceutics 2014, 11
(5)
, 1583-1590. https://doi.org/10.1021/mp400747k
- Federica Sgolastra, Lisa M. Minter, Barbara A. Osborne, and Gregory N. Tew . Importance of Sequence Specific Hydrophobicity in Synthetic Protein Transduction Domain Mimics. Biomacromolecules 2014, 15
(3)
, 812-820. https://doi.org/10.1021/bm401634r
- Megha Rajendran, Engin Yapici, and Lawrence W. Miller . Lanthanide-Based Imaging of Protein–Protein Interactions in Live Cells. Inorganic Chemistry 2014, 53
(4)
, 1839-1853. https://doi.org/10.1021/ic4018739
- Sílvia Pujals, Hiroki Miyamae, Sergii Afonin, Tomo Murayama, Hisaaki Hirose, Ikuhiko Nakase, Kentaro Taniuchi, Masato Umeda, Kazutami Sakamoto, Anne S. Ulrich, and Shiroh Futaki . Curvature Engineering: Positive Membrane Curvature Induced by Epsin N-Terminal Peptide Boosts Internalization of Octaarginine. ACS Chemical Biology 2013, 8
(9)
, 1894-1899. https://doi.org/10.1021/cb4002987
- Wei Qu, Wei-Hai Chen, Ying Kuang, Xuan Zeng, Si-Xue Cheng, Xiang Zhou, Ren-Xi Zhuo, and Xian-Zheng Zhang . Avidin–Biotin Interaction Mediated Peptide Assemblies as Efficient Gene Delivery Vectors for Cancer Therapy. Molecular Pharmaceutics 2013, 10
(1)
, 261-269. https://doi.org/10.1021/mp300392z
- Ikuhiko Nakase, Hidetaka Akita, Kentaro Kogure, Astrid Gräslund, Ülo Langel, Hideyoshi Harashima, and Shiroh Futaki . Efficient Intracellular Delivery of Nucleic Acid Pharmaceuticals Using Cell-Penetrating Peptides. Accounts of Chemical Research 2012, 45
(7)
, 1132-1139. https://doi.org/10.1021/ar200256e
- Katja Petkau-Milroy, Michael H. Sonntag, Arthur H. A. M. van Onzen, and Luc Brunsveld . Supramolecular Polymers as Dynamic Multicomponent Cellular Uptake Carriers. Journal of the American Chemical Society 2012, 134
(19)
, 8086-8089. https://doi.org/10.1021/ja3029075
- Kentaro Takayama, Hisaaki Hirose, Gen Tanaka, Sílvia Pujals, Sayaka Katayama, Ikuhiko Nakase, and Shiroh Futaki . Effect of the Attachment of a Penetration Accelerating Sequence and the Influence of Hydrophobicity on Octaarginine-Mediated Intracellular Delivery. Molecular Pharmaceutics 2012, 9
(5)
, 1222-1230. https://doi.org/10.1021/mp200518n
- Xiaona Jing, Marina R. Kasimova, Anders H. Simonsen, Lene Jorgensen, Martin Malmsten, Henrik Franzyk, Camilla Foged, and Hanne M. Nielsen . Interaction of Peptidomimetics with Bilayer Membranes: Biophysical Characterization and Cellular Uptake. Langmuir 2012, 28
(11)
, 5167-5175. https://doi.org/10.1021/la204033u
- André Ziegler and Joachim Seelig . Contributions of Glycosaminoglycan Binding and Clustering to the Biological Uptake of the Nonamphipathic Cell-Penetrating Peptide WR9. Biochemistry 2011, 50
(21)
, 4650-4664. https://doi.org/10.1021/bi1019429
- Tzu-Yuan Chao, Luke D. Lavis, and Ronald T. Raines . Cellular Uptake of Ribonuclease A Relies on Anionic Glycans. Biochemistry 2010, 49
(50)
, 10666-10673. https://doi.org/10.1021/bi1013485
- Dikran Sarko, Barbro Beijer, Regine Garcia Boy, Eva-Maria Nothelfer, Karin Leotta, Michael Eisenhut, Annette Altmann, Uwe Haberkorn, Walter Mier. The Pharmacokinetics of Cell-Penetrating Peptides. Molecular Pharmaceutics 2010, 7
(6)
, 2224-2231. https://doi.org/10.1021/mp100223d
- Patrick M. McLendon, Daniel J. Buckwalter, Erica M. Davis, and Theresa M. Reineke . Interaction of Poly(glycoamidoamine) DNA Delivery Vehicles with Cell-Surface Glycosaminoglycans Leads to Polyplex Internalization in a Manner Not Solely Dependent on Charge. Molecular Pharmaceutics 2010, 7
(5)
, 1757-1768. https://doi.org/10.1021/mp100135n
- Emelía Eiríksdóttir, Imre Mäger, Taavi Lehto, Samir El Andaloussi, and Ülo Langel . Cellular Internalization Kinetics of (Luciferin-)Cell-Penetrating Peptide Conjugates. Bioconjugate Chemistry 2010, 21
(9)
, 1662-1672. https://doi.org/10.1021/bc100174y
- Ya-Jung Lee, Gregory Johnson and Jean-Philippe Pellois. Modeling of the Endosomolytic Activity of HA2-TAT Peptides with Red Blood Cells and Ghosts. Biochemistry 2010, 49
(36)
, 7854-7866. https://doi.org/10.1021/bi1008408
- Partha Ghosh, Xiaochao Yang, Rochelle Arvizo, Zheng-Jiang Zhu, Sarit S. Agasti, Zhihong Mo and Vincent M. Rotello. Intracellular Delivery of a Membrane-Impermeable Enzyme in Active Form Using Functionalized Gold Nanoparticles. Journal of the American Chemical Society 2010, 132
(8)
, 2642-2645. https://doi.org/10.1021/ja907887z
- Craig P. Montgomery, Benjamin S. Murray, Elizabeth J. New, Robert Pal and David Parker. Cell-Penetrating Metal Complex Optical Probes: Targeted and Responsive Systems Based on Lanthanide Luminescence. Accounts of Chemical Research 2009, 42
(7)
, 925-937. https://doi.org/10.1021/ar800174z
- Cindy A. Puckett and Jacqueline K. Barton. Fluorescein Redirects a Ruthenium−Octaarginine Conjugate to the Nucleus. Journal of the American Chemical Society 2009, 131
(25)
, 8738-8739. https://doi.org/10.1021/ja9025165
- Judith Mueller, Ines Kretzschmar, Rudolf Volkmer and Prisca Boisguerin. Comparison of Cellular Uptake Using 22 CPPs in 4 Different Cell Lines. Bioconjugate Chemistry 2008, 19
(12)
, 2363-2374. https://doi.org/10.1021/bc800194e
- Hiroki Sakae, Yamato Takeuchi, Chitose Maruyama, Yoshimitsu Hamano, Hirohisa Nagatani. Ion transfer mechanism of fluorescence-labeled octa-arginine on model biomembrane surfaces. Journal of Electroanalytical Chemistry 2024, 970 , 118545. https://doi.org/10.1016/j.jelechem.2024.118545
- Stéphanie G. I. Polderdijk, Jazeel F. Limzerwala, Christoph Spiess, . Plasma membrane damage limits cytoplasmic delivery by conventional cell penetrating peptides. PLOS ONE 2024, 19
(9)
, e0305848. https://doi.org/10.1371/journal.pone.0305848
- Alexandre V. Ivachtchenko, Alexander V. Khvat, Dmitrii O. Shkil. Development and Prospects of Furin Inhibitors for Therapeutic Applications. International Journal of Molecular Sciences 2024, 25
(17)
, 9199. https://doi.org/10.3390/ijms25179199
- Linh D. Mai, Sydney C. Wimberley, Julie A. Champion. Intracellular delivery strategies using membrane-interacting peptides and proteins. Nanoscale 2024, 16
(33)
, 15465-15480. https://doi.org/10.1039/D4NR02093F
- Xiaodi Li, Shengnan Cheng, Chenggong Yu, Yuxuan Li, Xiaoling Cao, Yuhan Wang, Zhijun Zhang, Jie Huang. Co-delivery of retinoic acid and miRNA by functional Au nanoparticles for improved survival and CT imaging tracking of MSCs in pulmonary fibrosis therapy. Asian Journal of Pharmaceutical Sciences 2024, 19
(4)
, 100944. https://doi.org/10.1016/j.ajps.2024.100944
- Ruo‐Long Su, Xue‐Wei Cao, Jian Zhao, Fu‐Jun Wang. A high hydrophobic moment arginine‐rich peptide screened by a machine learning algorithm enhanced ADC antitumor activity. Journal of Peptide Science 2024, 8 https://doi.org/10.1002/psc.3628
- Akari Miwa, Koki Kamiya. Cell-Penetrating Peptide-Mediated Biomolecule Transportation in Artificial Lipid Vesicles and Living Cells. Molecules 2024, 29
(14)
, 3339. https://doi.org/10.3390/molecules29143339
- Sujin Park, Jinmin Kim, Seung Soo Oh, Siyoung Q. Choi. Arginine‐Rich Cell‐Penetrating Peptides Induce Lipid Rearrangements for Their Active Translocation across Laterally Heterogeneous Membranes. Advanced Science 2024, 14 https://doi.org/10.1002/advs.202404563
- Yuji Yamada. Characterization of Novel Cell-Adhesive Peptides for Biomaterial Development. Biological and Pharmaceutical Bulletin 2024, 47
(6)
, 1072-1078. https://doi.org/10.1248/bpb.b24-00030
- Astrid Walrant, Emmanuelle Sachon. Photoaffinity labeling coupled to MS to identify peptide biological partners: Secondary reactions, for better or for worse?. Mass Spectrometry Reviews 2024, 1 https://doi.org/10.1002/mas.21880
- Karima Tarchoun, Dóra Soltész, Viktor Farkas, Ho-Jin Lee, Ildikó Szabó, Zoltán Bánóczi. Influence of Aza-Glycine Substitution on the Internalization of Penetratin. Pharmaceutics 2024, 16
(4)
, 477. https://doi.org/10.3390/pharmaceutics16040477
- Andrea Barba‐Bon, Nadiia I. Gumerova, Elias Tanuhadi, Maryam Ashjari, Yao Chen, Annette Rompel, Werner M. Nau. All‐Inorganic Polyoxometalates Act as Superchaotropic Membrane Carriers. Advanced Materials 2024, 36
(1)
https://doi.org/10.1002/adma.202309219
- Alexander Chan, Andrew Tsourkas. Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications. BME Frontiers 2024, 5 https://doi.org/10.34133/bmef.0035
- Seong Guk Park, Hyun Bin Lee, Sebyung Kang. Development of plug-and-deliverable intracellular protein delivery platforms based on botulinum neurotoxin. International Journal of Biological Macromolecules 2024, 20 , 129622. https://doi.org/10.1016/j.ijbiomac.2024.129622
- Joshua Diaz, Jean-Philippe Pellois. Deciphering variations in the endocytic uptake of a cell-penetrating peptide: the crucial role of cell culture protocols. Cytotechnology 2023, 75
(6)
, 473-490. https://doi.org/10.1007/s10616-023-00591-1
- Jeffrey W. Wang, Henry J. Squire, Natalie S. Goh, Heyuan Michael Ni, Edward Lien, Cerise Wong, Eduardo González-Grandío, Markita P. Landry. Delivered complementation in planta (DCIP) enables measurement of peptide-mediated protein delivery efficiency in plants. Communications Biology 2023, 6
(1)
https://doi.org/10.1038/s42003-023-05191-5
- Tingting Zhang, Xuan Luo, Keming Xu, Wenying Zhong. Peptide-containing nanoformulations: Skin barrier penetration and activity contribution. Advanced Drug Delivery Reviews 2023, 203 , 115139. https://doi.org/10.1016/j.addr.2023.115139
- Koji Kadota, Toshiki Mikami, Ai Kohata, Jumpei Morimoto, Shinsuke Sando, Kohsuke Aikawa, Takashi Okazoe. Synthesis of Short Peptides with Perfluoroalkyl Side Chains and Evaluation of Their Cellular Uptake Efficiency. ChemBioChem 2023, 24
(21)
https://doi.org/10.1002/cbic.202300374
- Valeria Graceffa. Intracellular protein delivery: New insights into the therapeutic applications and emerging technologies. Biochimie 2023, 213 , 82-99. https://doi.org/10.1016/j.biochi.2023.05.011
- Jianhua Lv, Pan Wu, Yaru Fang, Wenchang Zhang, Dongwen Liu, Mi Wu, Lei Shang, Huaiguo Li, Yan Zhao. Deep Eutectic Solvents Based on L-Arginine and 2-Hydroxypropyl-β-Cyclodextrin for Drug Carrier and Penetration Enhancement. AAPS PharmSciTech 2023, 24
(7)
https://doi.org/10.1208/s12249-023-02638-0
- Florina Zakany, István M. Mándity, Zoltan Varga, Gyorgy Panyi, Peter Nagy, Tamas Kovacs. Effect of the Lipid Landscape on the Efficacy of Cell-Penetrating Peptides. Cells 2023, 12
(13)
, 1700. https://doi.org/10.3390/cells12131700
- Jiangkang Xu, Fenghua Wang, Lei Ye, Rui Wang, Lixia Zhao, Xiaoye Yang, Jianbo Ji, Anchang Liu, Guangxi Zhai. Penetrating peptides: Applications in drug delivery. Journal of Drug Delivery Science and Technology 2023, 84 , 104475. https://doi.org/10.1016/j.jddst.2023.104475
- Yangjun Feng, Xiaolin Li, Dongsheng Ji, Jialei Tian, Qian Peng, Yuzhen Shen, Yuliang Xiao. Functionalised penetrating peptide-chondroitin sulphate‑gold nanoparticles: Synthesis, characterization, and applications as an anti-Alzheimer's disease drug. International Journal of Biological Macromolecules 2023, 230 , 123125. https://doi.org/10.1016/j.ijbiomac.2022.123125
- Marc Serulla, Palapuravan Anees, Ali Hallaj, Evgeniya Trofimenko, Tara Kalia, Yamuna Krishnan, Christian Widmann. Plasma membrane depolarization reveals endosomal escape incapacity of cell-penetrating peptides. European Journal of Pharmaceutics and Biopharmaceutics 2023, 184 , 116-124. https://doi.org/10.1016/j.ejpb.2023.01.019
- Ikuhiko Nakase. Cellular Uptake Mechanisms of Arginine‐Rich Cell‐Penetrating Peptides. 2023, 141-157. https://doi.org/10.1002/9783527835997.ch9
- Micael G. Gouveia, Justus P. Wesseler, Jobbe Ramaekers, Christoph Weder, Philip B. V. Scholten, Nico Bruns. Polymersome-based protein drug delivery – quo vadis?. Chemical Society Reviews 2023, 52
(2)
, 728-778. https://doi.org/10.1039/D2CS00106C
- Ülo Langel. Classes and Applications of Cell-Penetrating Peptides. 2023, 43-82. https://doi.org/10.1007/978-3-031-38731-9_2
- R. Rotem, J.A. Bertolini, L. Salvioni, L. Barbieri, M.A. Rizzuto, V. Tinelli, A. Gori, S. Adams, M. Colombo, D. Prosperi. Direct quantification of cytosolic delivery of drug nanocarriers using FlAsH-EDT2. Nanomedicine: Nanotechnology, Biology and Medicine 2023, 47 , 102626. https://doi.org/10.1016/j.nano.2022.102626
- Yamato Takeuchi, Kazunori Ushimaru, Kohei Kaneda, Chitose Maruyama, Takashi Ito, Kazuya Yamanaka, Yasushi Ogasawara, Hajime Katano, Yasuo Kato, Tohru Dairi, Yoshimitsu Hamano. First direct evidence for direct cell-membrane penetrations of polycationic homopoly(amino acid)s produced by bacteria. Communications Biology 2022, 5
(1)
https://doi.org/10.1038/s42003-022-04110-4
- Si-Yi Chen, Xiao-Xue Xu, Xin Li, Ning-Bo Yi, Shi-Zhuo Li, Xing-Cheng Xiang, Dong-Bing Cheng, Taolei Sun. Recent advances in the intracellular delivery of macromolecule therapeutics. Biomaterials Science 2022, 10
(23)
, 6642-6655. https://doi.org/10.1039/D2BM01348G
- Abhishek Saha, Shaswati Mandal, Jan Vincent V. Arafiles, Jacobo Gómez‐González, Christian P. R. Hackenberger, Ashraf Brik. Struktur‐Wirkungsbeziehung von an zyklische Zell‐penetrierende Peptide gebundenen DABCYL‐Derivaten für den Transport von synthetischen Proteinen in lebende Zellen. Angewandte Chemie 2022, 134
(47)
https://doi.org/10.1002/ange.202207551
- Abhishek Saha, Shaswati Mandal, Jan Vincent V. Arafiles, Jacobo Gómez‐González, Christian P. R. Hackenberger, Ashraf Brik. Structure–Uptake Relationship Study of DABCYL Derivatives Linked to Cyclic Cell‐Penetrating Peptides for Live‐Cell Delivery of Synthetic Proteins. Angewandte Chemie International Edition 2022, 61
(47)
https://doi.org/10.1002/anie.202207551
- Syusuke Okano, Yoshimasa Kawaguchi, Kenichi Kawano, Hisaaki Hirose, Miki Imanishi, Shiroh Futaki. Split luciferase-based estimation of cytosolic cargo concentration delivered intracellularly via attenuated cationic amphiphilic lytic peptides. Bioorganic & Medicinal Chemistry Letters 2022, 72 , 128875. https://doi.org/10.1016/j.bmcl.2022.128875
- Chun Yin Jerry Lau, Naomi Benne, Bo Lou, Olga Zharkova, Hui Jun Ting, Daniëlle ter Braake, Nicky van Kronenburg, Marcel H. Fens, Femke Broere, Wim E. Hennink, Jiong-Wei Wang, Enrico Mastrobattista. Modulating albumin-mediated transport of peptide-drug conjugates for antigen-specific Treg induction. Journal of Controlled Release 2022, 348 , 938-950. https://doi.org/10.1016/j.jconrel.2022.06.025
- Minglu Hao, Lei Zhang, Pu Chen. Membrane Internalization Mechanisms and Design Strategies of Arginine-Rich Cell-Penetrating Peptides. International Journal of Molecular Sciences 2022, 23
(16)
, 9038. https://doi.org/10.3390/ijms23169038
- Sunam Mander, Samer A. Naffouje, Jin Gao, Weiguo Li, Konstantin Christov, Albert Green, Ernesto R. Bongarzone, Tapas K. Das Gupta, Tohru Yamada. Tumor-targeting cell-penetrating peptide, p28, for glioblastoma imaging and therapy. Frontiers in Oncology 2022, 12 https://doi.org/10.3389/fonc.2022.940001
- S Selva Rani, M Shanthi, M Murugan, K Senthil, S Vellaikumar, S Haripriya. Bioefficacy of novel arginine-rich chitosan against Diamondback moth, Plutella xylostella L. (Lepidoptera: Plutellidae) infesting cauliflower. International Journal of Tropical Insect Science 2022, 42
(3)
, 2455-2464. https://doi.org/10.1007/s42690-022-00772-z
- Kenta Shinga, Takahiro Iwata, Kazuya Murata, Yoko Daitoku, Junya Michibata, Jan Vincent V. Arafiles, Kentarou Sakamoto, Misao Akishiba, Tomoka Takatani-Nakase, Seiya Mizuno, Fumihiro Sugiyama, Miki Imanishi, Shiroh Futaki. L17ER4: A cell-permeable attenuated cationic amphiphilic lytic peptide. Bioorganic & Medicinal Chemistry 2022, 61 , 116728. https://doi.org/10.1016/j.bmc.2022.116728
- Ildikó Szabó, Mo’ath Yousef, Dóra Soltész, Csaba Bató, Gábor Mező, Zoltán Bánóczi. Redesigning of Cell-Penetrating Peptides to Improve Their Efficacy as a Drug Delivery System. Pharmaceutics 2022, 14
(5)
, 907. https://doi.org/10.3390/pharmaceutics14050907
- Jun Wang, Guang Chen, Nan Liu, Xiaoxia Han, Feng Zhao, Lei Zhang, P. Chen. Strategies for improving the safety and RNAi efficacy of noncovalent peptide/siRNA nanocomplexes. Advances in Colloid and Interface Science 2022, 302 , 102638. https://doi.org/10.1016/j.cis.2022.102638
Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.
Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.
The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.