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Cellular Internalization and Distribution of Arginine-Rich Peptides as a Function of Extracellular Peptide Concentration, Serum, and Plasma Membrane Associated Proteoglycans

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Download Hi-Res ImageDownload to MS-PowerPointCite This:Bioconjugate Chem. 2008, 19, 3, 656-664
    Article

    Cellular Internalization and Distribution of Arginine-Rich Peptides as a Function of Extracellular Peptide Concentration, Serum, and Plasma Membrane Associated Proteoglycans
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    Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan, SORST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan, and Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3XF, Wales, United Kingdom
    * To whom correspondence should be addressed: Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan. Tel: +81-774-38-3210 , Fax: +81-774-32-3038, E-mail: [email protected]
    †Kyoto University.
    ‡JST.
    §Cardiff University.
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    Bioconjugate Chemistry

    Cite this: Bioconjugate Chem. 2008, 19, 3, 656–664
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    https://doi.org/10.1021/bc700289w
    Published February 13, 2008
    Copyright © 2008 American Chemical Society
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    Abstract

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    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.

    Copyright © 2008 American Chemical Society

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    Supporting Information

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    Methods of peptide synthesis and fluorescence labeling, preparation of EGFP protein, MTT and LDH release assays, and Figure S1. This material is available free of charge via the Internet at http://pubs.acs.org/BC.

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    This article is cited by 290 publications.

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    65. 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
    66. 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
    67. 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
    68. 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
    69. 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
    70. 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
    71. 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
    72. 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
    73. Alexander Chan, Andrew Tsourkas. Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications. BME Frontiers 2024, 5 https://doi.org/10.34133/bmef.0035
    74. 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
    75. 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
    76. 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
    77. 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
    78. 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
    79. 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
    80. 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
    81. 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
    82. 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
    83. 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
    84. 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
    85. Ikuhiko Nakase. Cellular Uptake Mechanisms of Arginine‐Rich Cell‐Penetrating Peptides. 2023, 141-157. https://doi.org/10.1002/9783527835997.ch9
    86. 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
    87. Ülo Langel. Classes and Applications of Cell-Penetrating Peptides. 2023, 43-82. https://doi.org/10.1007/978-3-031-38731-9_2
    88. 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
    89. 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
    90. 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
    91. 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
    92. 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
    93. 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
    94. 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
    95. 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
    96. 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
    97. 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
    98. 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
    99. 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
    100. 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
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    Bioconjugate Chemistry

    Cite this: Bioconjugate Chem. 2008, 19, 3, 656–664
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    https://doi.org/10.1021/bc700289w
    Published February 13, 2008
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