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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Review Article

Cell-Penetrating Peptides: A Powerful Tool for Targeted Drug Delivery

Author(s): Dushyant D. Kotadiya, Piyushkumar Patel and Hitesh D. Patel*

Volume 21, Issue 3, 2024

Published on: 27 April, 2023

Page: [368 - 388] Pages: 21

DOI: 10.2174/1567201820666230407092924

Price: $65

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Abstract

The cellular membrane hinders the effective delivery of therapeutics to targeted sites. Cellpenetrating peptide (CPP) is one of the best options for rapidly internalizing across the cellular membrane. CPPs have recently attracted lots of attention because of their excellent transduction efficiency and low cytotoxicity. The CPP-cargo complex is an effective and efficient method of delivering several chemotherapeutic agents used to treat various diseases. Additionally, CPP has become another strategy to overcome some of the current therapeutic agents' limitations. However, no CPP complex is approved by the US FDA because of its limitations and issues. In this review, we mainly discuss the cellpenetrating peptide as the delivery vehicle, the cellular uptake mechanism of CPPs, their design, and some strategies to synthesize the CPP complex via some linkers such as disulfide bond, oxime, etc. Here, we also discuss the recent status of CPPs in the market.

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[1]
Pran, K.D.; Al-Attraqchi, O.; Chandrasekaran, B.; Paradkar, A.; Tekade, R.K. Protein/Peptide Drug Delivery Systems: Practical Considerations in Pharmaceutical Product Development. In: Advances in Pharmaceutical Product Development and Research, Basic Fundamentals of Drug Delivery; Academic Press, 2019; pp. 651-684.
[http://dx.doi.org/10.1016/B978-0-12-817909-3.00016-9]
[2]
Swain, S.; Sahu, P.; Beg, S.; Babu, S. Nanoparticles for cancer targeting: Current and future directions. Curr. Drug Deliv., 2016, 13(8), 1290-1302.
[http://dx.doi.org/10.2174/1567201813666160713121122] [PMID: 27411485]
[3]
Borrelli, A.; Tornesello, A.; Tornesello, M.; Buonaguro, F. Cell penetrating peptides as molecular carriers for anti-cancer agents. Molecules, 2018, 23(2), 295.
[http://dx.doi.org/10.3390/molecules23020295] [PMID: 29385037]
[4]
Fatemeh, M.; Lindberg, S.; Langel, U.; Futaki, S. Mechanisms of cellular uptake of cell-penetrating peptides. Biophys. J., 2011, 2011, 414729.
[http://dx.doi.org/10.1155/2011/414729]
[5]
Schaffhausen, J. Remaining hurdles to effective cancer therapy. Trends Pharmacol. Sci., 2015, 36(6), v.
[http://dx.doi.org/10.1016/j.tips.2015.04.008] [PMID: 25959521]
[6]
Rodríguez, V.; Lascani, J.; Asenjo, J.A.; Andrews, B.A. Production of cell-penetrating peptides in Escherichia coli using an intein-mediated system. Appl. Biochem. Biotechnol., 2015, 175(6), 3025-3037.
[http://dx.doi.org/10.1007/s12010-015-1484-7] [PMID: 25586490]
[7]
Martin, M.E.; Rice, K.G. Peptide-guided gene delivery. AAPS J., 2007, 9(1), E18-E29.
[http://dx.doi.org/10.1208/aapsj0901003] [PMID: 17408236]
[8]
Xie, J.; Bi, Y.; Zhang, H.; Dong, S.; Teng, L.; Lee, R.J.; Yang, Z. Cell-penetrating peptides in diagnosis and treatment of human diseases: From preclinical research to clinical application. Front. Pharmacol., 2020, 11, 697.
[http://dx.doi.org/10.3389/fphar.2020.00697] [PMID: 32508641]
[9]
Frankel, A.D.; Pabo, C.O. Cellular uptake of the tat protein from human immunodeficiency virus. Cell, 1988, 55(6), 1189-1193.
[http://dx.doi.org/10.1016/0092-8674(88)90263-2] [PMID: 2849510]
[10]
Meong, C.S.; Jian, Z.; David, A.E.; Wolfgang, E.T.; Young, M.K. Chemically and Biologically Synthesized CPP-Modified Gelonin for Enhanced Anti-tumor Activity. J. Control. Release, 2013, 172(1), 169-178. ISSN 0168-3659
[http://dx.doi.org/10.1016/j.jconrel.2013.08.016]
[11]
Gemma, C.B.; Julia, M.; Periyasamy, K.; Urgard, E.; Padari, K.; Vaher, H.; Tserel, L.; Gestin, M.; Kisand, K.; Arukuusk, P.; Chenguang, L.; Ülo, L.; Jesper, W.; Margus, P.; Ana, R. NickFect type of cell-penetrating peptides present enhanced efficiency for microRNA-146a delivery into dendritic cells and during skin inflammation. Biomaterials, 2020, 262, 120316.
[http://dx.doi.org/10.1016/j.biomaterials.2020.120316]
[12]
Joliot, A.; Pernelle, C.; Deagostini-Bazin, H.; Prochiantz, A. Antennapedia homeobox peptide regulates neural morphogenesis. Proc. Natl. Acad. Sci., 1991, 88(5), 1864-1868.
[http://dx.doi.org/10.1073/pnas.88.5.1864] [PMID: 1672046]
[13]
Van Nguyen, T.; Shin, M.C.; Min, K.A.; Huang, Y.; Oh, E.; Moon, C. Cell-penetrating peptide-based non-invasive topical delivery systems. J. Pharm. Investig., 2018, 48(1), 77-87.
[http://dx.doi.org/10.1007/s40005-017-0373-1]
[14]
Stewart, K.M.; Horton, K.L.; Kelley, S.O. Cell-penetrating peptides as delivery vehicles for biology and medicine. Org. Biomol. Chem., 2008, 6(13), 2242-2255.
[http://dx.doi.org/10.1039/b719950c] [PMID: 18563254]
[15]
Silva, S.; Almeida, A.; Vale, N. Combination of cell-penetrating peptides with nanoparticles for therapeutic application: A review. Biomolecules, 2019, 9(1), 22.
[http://dx.doi.org/10.3390/biom9010022] [PMID: 30634689]
[16]
El-Andaloussi, S.; Holm, T.; Langel, U. Cell-penetrating peptides: Mechanisms and applications. Curr. Pharm. Des., 2005, 11(28), 3597-3611.
[http://dx.doi.org/10.2174/138161205774580796] [PMID: 16305497]
[17]
Traub, L.M. Tickets to ride: Selecting cargo for clathrin-regulated internalization. Nat. Rev. Mol. Cell Biol., 2009, 10(9), 583-596.
[http://dx.doi.org/10.1038/nrm2751] [PMID: 19696796]
[18]
Mitchell, D.J.; Steinman, L.; Kim, D.T.; Fathman, C.G.; Rothbard, J.B. Polyarginine enters cells more efficiently than other polycationic homopolymers. J. Pept. Res., 2000, 56(5), 318-325.
[http://dx.doi.org/10.1034/j.1399-3011.2000.00723.x] [PMID: 11095185]
[19]
Crombez, L.; Aldrian-Herrada, G.; Konate, K.; Nguyen, Q.N.; McMaster, G.K.; Brasseur, R.; Heitz, F.; Divita, G. A new potent secondary amphipathic cell-penetrating peptide for siRNA delivery into mammalian cells. Mol. Ther., 2009, 17(1), 95-103.
[http://dx.doi.org/10.1038/mt.2008.215] [PMID: 18957965]
[20]
Ramsey, J.D.; Flynn, N.H. Cell-penetrating peptides transport therapeutics into cells. Pharmacol. Ther., 2015, 154, 78-86.
[http://dx.doi.org/10.1016/j.pharmthera.2015.07.003] [PMID: 26210404]
[21]
Zhang, D.; Wang, J.; Xu, D. Cell-penetrating peptides as noninvasive transmembrane vectors for the development of novel multifunctional drug-delivery systems. J. Control. Release, 2016, 229, 130-139.
[http://dx.doi.org/10.1016/j.jconrel.2016.03.020] [PMID: 26993425]
[22]
Milletti, F. Cell-penetrating peptides: Classes, origin, and current landscape. Drug Discov. Today, 2012, 17(15-16), 850-860.
[http://dx.doi.org/10.1016/j.drudis.2012.03.002] [PMID: 22465171]
[23]
Green, M.; Ishino, M.; Loewenstein, P.M. Mutational analysis of HIV-1 Tat minimal domain peptides: Identification of trans-dominant mutants that suppress HIV-LTR-driven gene expression. Cell, 1989, 58(1), 215-223.
[http://dx.doi.org/10.1016/0092-8674(89)90417-0] [PMID: 2752420]
[24]
Futaki, S.; Suzuki, T.; Ohashi, W.; Yagami, T.; Tanaka, S.; Ueda, K.; Sugiura, Y. Arginine-rich Peptides. J. Biol. Chem., 2001, 276(8), 5836-5840.
[http://dx.doi.org/10.1074/jbc.M007540200] [PMID: 11084031]
[25]
Mueller, J.; Kretzschmar, I.; Volkmer, R.; Boisguerin, P. Comparison of cellular uptake using 22 CPPs in 4 different cell lines. Bioconjug. Chem., 2008, 19(12), 2363-2374.
[http://dx.doi.org/10.1021/bc800194e] [PMID: 19053306]
[26]
Schafmeister, C.E.; Po, J.; Verdine, G.L. An all-hydrocarbon cross-linking system for Enhancing the helicity and metabolic stability of peptides. J. Am. Chem. Soc., 2000, 122(24), 5891-5892.
[http://dx.doi.org/10.1021/ja000563a]
[27]
Bernal, F.; Tyler, A.F.; Korsmeyer, S.J.; Walensky, L.D.; Verdine, G.L. Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide. J. Am. Chem. Soc., 2007, 129(9), 2456-2457.
[http://dx.doi.org/10.1021/ja0693587] [PMID: 17284038]
[28]
Marks, J.R.; Placone, J.; Hristova, K.; Wimley, W.C. Spontaneous membrane-translocating peptides by orthogonal high-throughput screening. J. Am. Chem. Soc., 2011, 133(23), 8995-9004.
[http://dx.doi.org/10.1021/ja2017416] [PMID: 21545169]
[29]
Dougherty, P.G.; Sahni, A.; Pei, D. Understanding cell penetration of cyclic peptides. Chem. Rev., 2019, 119(17), 10241-10287.
[http://dx.doi.org/10.1021/acs.chemrev.9b00008] [PMID: 31083977]
[30]
Qian, Z.; Martyna, A.; Hard, R.L.; Wang, J.; Appiah-Kubi, G.; Coss, C.; Phelps, M.A.; Rossman, J.S.; Pei, D. Discovery and mechanism of highly efficient cyclic cell-penetrating peptides. Biochemistry, 2016, 55(18), 2601-2612.
[http://dx.doi.org/10.1021/acs.biochem.6b00226] [PMID: 27089101]
[31]
Schwarze, S.R.; Ho, A.; Vocero-Akbani, A.; Dowdy, S.F. In vivo protein transduction: Delivery of a biologically active protein into the mouse. Science, 1999, 285(5433), 1569-1572.
[http://dx.doi.org/10.1126/science.285.5433.1569] [PMID: 10477521]
[32]
Derossi, D.; Joliot, A.H.; Chassaing, G.; Prochiantz, A. The third helix of the antennapedia homeodomain translocates through biological membranes. J. Biol. Chem., 1994, 269(14), 10444-10450.
[http://dx.doi.org/10.1016/S0021-9258(17)34080-2] [PMID: 8144628]
[33]
Elliott, G.; O’Hare, P. Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell, 1997, 88(2), 223-233.
[http://dx.doi.org/10.1016/S0092-8674(00)81843-7] [PMID: 9008163]
[34]
Elmquist, A.; Lindgren, M.; Bartfai, T.; Langel, Ü. VE-cadherin-derived cell-penetrating peptide, pVEC, with carrier functions. Exp. Cell Res., 2001, 269(2), 237-244.
[http://dx.doi.org/10.1006/excr.2001.5316] [PMID: 11570816]
[35]
Lindgren, M.; Gallet, X.; Soomets, U.; Hällbrink, M.; Bråkenhielm, E.; Pooga, M.; Brasseur, R.; Langel, Ü. Translocation properties of novel cell penetrating transportan and penetratin analogues. Bioconjug. Chem., 2000, 11(5), 619-626.
[http://dx.doi.org/10.1021/bc990156s] [PMID: 10995204]
[36]
Soomets, U.; Lindgren, M.; Gallet, X.; Hällbrink, M.; Elmquist, A.; Balaspiri, L.; Zorko, M.; Pooga, M.; Brasseur, R.; Langel, Ü. Deletion analogues of transportan. Biochim. Biophys. Acta Biomembr., 2000, 1467(1), 165-176.
[http://dx.doi.org/10.1016/S0005-2736(00)00216-9] [PMID: 10930519]
[37]
Wender, P.A.; Cooley, C.B.; Geihe, E.I. Beyond cell penetrating peptides: Designed molecular transporters. Drug Discov. Today. Technol., 2012, 9(1), e49-e55.
[http://dx.doi.org/10.1016/j.ddtec.2011.07.004] [PMID: 22712022]
[38]
Gros, E.; Deshayes, S.; Morris, M.C.; Aldrian-Herrada, G.; Depollier, J.; Heitz, F.; Divita, G. A non-covalent peptide-based strategy for protein and peptide nucleic acid transduction. Biochim. Biophys. Acta Biomembr., 2006, 1758(3), 384-393.
[http://dx.doi.org/10.1016/j.bbamem.2006.02.006] [PMID: 16545342]
[39]
Rhee, M.; Davis, P. Mechanism of uptake of C105Y, a novel cell-penetrating peptide. J. Biol. Chem., 2006, 281(2), 1233-1240.
[http://dx.doi.org/10.1074/jbc.M509813200] [PMID: 16272160]
[40]
Kalafut, D.; Anderson, T.N.; Chmielewski, J. Mitochondrial targeting of a cationic amphiphilic polyproline helix. Bioorg. Med. Chem. Lett., 2012, 22(1), 561-563.
[http://dx.doi.org/10.1016/j.bmcl.2011.10.077] [PMID: 22130131]
[41]
Veiman, K.L.; Künnapuu, K.; Lehto, T.; Kiisholts, K.; Pärn, K.; Langel, Ü.; Kurrikoff, K. PEG shielded MMP sensitive CPPs for efficient and tumor specific gene delivery in vivo. J. Control. Release, 2015, 209, 238-247.
[http://dx.doi.org/10.1016/j.jconrel.2015.04.038] [PMID: 25935707]
[42]
Di Pisa, M.; Chassaing, G.; Swiecicki, J.M. Translocation mechanism(s) of cell-penetrating peptides: biophysical studies using artificial membrane bilayers. Biochemistry, 2015, 54(2), 194-207.
[http://dx.doi.org/10.1021/bi501392n] [PMID: 25490050]
[43]
Kauffman, W.B.; Fuselier, T.; He, J.; Wimley, W.C. Mechanism matters: A taxonomy of cell penetrating peptides. Trends Biochem. Sci., 2015, 40(12), 749-764.
[http://dx.doi.org/10.1016/j.tibs.2015.10.004] [PMID: 26545486]
[44]
Eiríksdóttir, E.; Konate, K.; Langel, Ü.; Divita, G.; Deshayes, S. Secondary structure of cell-penetrating peptides controls membrane interaction and insertion. Biochim. Biophys. Acta Biomembr., 2010, 1798(6), 1119-1128.
[http://dx.doi.org/10.1016/j.bbamem.2010.03.005] [PMID: 20214875]
[45]
Lindgren, M.; Langel, Ü. Classes and prediction of cell-penetrating peptides. In: Cell-Penetrating Peptides; Humana Press: New York, USA, 2011; 683, pp. 3-19.
[http://dx.doi.org/10.1007/978-1-60761-919-2_1]
[46]
Jones, A.T.; Sayers, E.J. Cell entry of cell penetrating peptides: tales of tails wagging dogs. J. Control. Release, 2012, 161(2), 582-591.
[http://dx.doi.org/10.1016/j.jconrel.2012.04.003] [PMID: 22516088]
[47]
Jha, D.; Mishra, R.; Gottschalk, S.; Wiesmüller, K.H.; Ugurbil, K.; Maier, M.E.; Engelmann, J. CyLoP-1: a novel cysteine-rich cell-penetrating peptide for cytosolic delivery of cargoes. Bioconjug. Chem., 2011, 22(3), 319-328.
[http://dx.doi.org/10.1021/bc100045s] [PMID: 21319732]
[48]
Fernández-Carneado, J.; Kogan, M.J.; Van Mau, N.; Pujals, S.; López-Iglesias, C.; Heitz, F.; Giralt, E. Fatty acyl moieties: Improving Pro-rich peptide uptake inside HeLa cells. J. Pept. Res., 2005, 65(6), 580-590.
[http://dx.doi.org/10.1111/j.1399-3011.2005.00253.x] [PMID: 15885117]
[49]
Regberg, J.; Srimanee, A.; Langel, Ü. Applications of cell-penetrating peptides for tumor targeting and future cancer therapies. Pharmaceuticals, 2012, 5(9), 991-1007.
[http://dx.doi.org/10.3390/ph5090991] [PMID: 24280701]
[50]
Shi, Y.; Hu, Y.; Ochbaum, G.; Lin, R.; Bitton, R.; Cui, H.; Azevedo, H.S. Enzymatic activation of cell-penetrating peptides in self-assembled nanostructures triggers fibre-to-micelle morphological transition. Chem. Commun., 2017, 53(52), 7037-7040.
[http://dx.doi.org/10.1039/C7CC03512H] [PMID: 28613294]
[51]
Tünnemann, G.; Ter-Avetisyan, G.; Martin, R.M.; Stöckl, M.; Herrmann, A.; Cardoso, M.C. Live-cell analysis of cell penetration ability and toxicity of oligo-arginines. J. Pept. Sci., 2008, 14(4), 469-476.
[http://dx.doi.org/10.1002/psc.968] [PMID: 18069724]
[52]
Herce, H.D.; Garcia, A.E.; Litt, J.; Kane, R.S.; Martin, P.; Enrique, N.; Rebolledo, A.; Milesi, V. Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides. Biophys. J., 2009, 97(7), 1917-1925.
[http://dx.doi.org/10.1016/j.bpj.2009.05.066] [PMID: 19804722]
[53]
Kölmel, D.K.; Hörner, A.; Rönicke, F.; Nieger, M.; Schepers, U.; Bräse, S. Cell-penetrating peptoids: Introduction of novel cationic side chains. Eur. J. Med. Chem., 2014, 79, 231-243.
[http://dx.doi.org/10.1016/j.ejmech.2014.03.078] [PMID: 24739871]
[54]
Kamide, K.; Nakakubo, H.; Uno, S.; Fukamizu, A. Isolation of novel cell-penetrating peptides from a random peptide library using in vitro virus and their modifications. Int. J. Mol. Med., 2010, 25(1), 41-51.
[PMID: 19956900]
[55]
Henriques, S.T.; Castanho, M.A.R.B. Translocation or membrane disintegration? Implication of peptide-membrane interactions in pep-1 activity. J. Pept. Sci., 2008, 14(4), 482-487.
[http://dx.doi.org/10.1002/psc.1003] [PMID: 18181239]
[56]
Delcroix, M.; Riley, L.W. cell penetrating peptides for antiviral drug development. Pharmaceuticals, 2010, 3(3), 448-470.
[http://dx.doi.org/10.3390/ph3030448] [PMID: 27713263]
[57]
Mishra, A.; Lai, G.H.; Schmidt, N.W.; Sun, V.Z.; Rodriguez, A.R.; Tong, R.; Tang, L.; Cheng, J.; Deming, T.J.; Kamei, D.T.; Wong, G.C.L. Translocation of HIV TAT peptide and analogues induced by multiplexed membrane and cytoskeletal interactions. Proc. Natl. Acad. Sci., 2011, 108(41), 16883-16888.
[http://dx.doi.org/10.1073/pnas.1108795108] [PMID: 21969533]
[58]
Fei, L.; Zaro, J.; Shen, W-c. Acid-labile modification of a cell penetrating peptide for use in targeted drug delivery; Biopharmaceutics,AAPS Annual Meeting and Exposition; Los Angeles, USA, 2009.
[59]
Mäe, M.; Myrberg, H.; El-Andaloussi, S.; Langel, Ü. langel, U. desing of tumor homing cell penetrating peptide for drug delivery. Int. J. Pept. Res. Ther., 2009, 15(1), 11-15.
[http://dx.doi.org/10.1007/s10989-008-9156-x]
[60]
Gupta, B.; Levchenko, T.; Torchilin, V. Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. Adv. Drug Deliv. Rev., 2005, 57(4), 637-651.
[http://dx.doi.org/10.1016/j.addr.2004.10.007] [PMID: 15722168]
[61]
Oehlke, J.; Scheller, A.; Wiesner, B.; Krause, E.; Beyermann, M.; Klauschenz, E.; Melzig, M.; Bienert, M. Cellular uptake of an α-helical amphipathic model peptide with the potential to deliver polar compounds into the cell interior non-endocytically. Biochim. Biophys. Acta Biomembr., 1998, 1414(1-2), 127-139.
[http://dx.doi.org/10.1016/S0005-2736(98)00161-8] [PMID: 9804921]
[62]
Fischer, R.; Fotin-Mleczek, M.; Hufnagel, H.; Brock, R. Break on through to the other side-biophysics and cell biology shed light on cell-penetrating peptides. ChemBioChem, 2005, 6(12), 2126-2142.
[http://dx.doi.org/10.1002/cbic.200500044] [PMID: 16254940]
[63]
Patel, L.N.; Zaro, J.L.; Shen, W.C. Peptides, C.P. intracellular pathways and pharmaceutical perspectives. Pharm. Res., 2007, 24, 1977-1992.
[http://dx.doi.org/10.1007/s11095-007-9303-7] [PMID: 17443399]
[64]
Matsuzaki, K.; Yoneyama, S.; Murase, O.; Miyajima, K. Transbilayer transport of ions and lipids coupled with mastoparan X translocation. Biochemistry, 1996, 35(25), 8450-8456.
[http://dx.doi.org/10.1021/bi960342a] [PMID: 8679603]
[65]
Pouny, Y.; Rapaport, D.; Mor, A.; Nicolas, P.; Shai, Y. Interaction of antimicrobial dermaseptin and its fluorescently labeled analogs with phospholipid membranes. Biochemistry, 1992, 31(49), 12416-12423.
[http://dx.doi.org/10.1021/bi00164a017] [PMID: 1463728]
[66]
Khandia, R.; Munjal, A.; Kumar, A.; Singh, G.; Karthik, K.; Dhama, K. Cell penetrating peptides: Biomedical/therapeutic applications with emphasis as promising futuristic hope for treating cancer. Int. J. Pharmacol., 2017, 13(7), 677-689.
[http://dx.doi.org/10.3923/ijp.2017.677.689]
[67]
Derossi, D.; Chassaing, G.; Prochiantz, A. Trojan peptides: the penetratin system for intracellular delivery. Trends Cell Biol., 1998, 8(2), 84-87.
[http://dx.doi.org/10.1016/S0962-8924(98)80017-2] [PMID: 9695814]
[68]
Elmquist, A. Cell-penetrating peptides: Cellular uptake and bioLogical activities, PhD Thesis, Stockholm University: Stockholm, 2003.
[69]
Islam, M.Z.; Sharmin, S.; Moniruzzaman, M.; Yamazaki, M. Elementary processes for the entry of cell-penetrating peptides into lipid bilayer vesicles and bacterial cells. Appl. Microbiol. Biotechnol., 2018, 102(9), 3879-3892.
[http://dx.doi.org/10.1007/s00253-018-8889-5] [PMID: 29523934]
[70]
Futaki, S.; Nakase, I.; Tadokoro, A.; Takeuchi, T.; Jones, A.T. Arginine-rich peptides and their internalization mechanisms. Biochem. Soc. Trans., 2007, 35(4), 784-787.
[http://dx.doi.org/10.1042/BST0350784] [PMID: 17635148]
[71]
Richard, J.P.; Melikov, K.; Vives, E.; Ramos, C.; Verbeure, B.; Gait, M.J.; Chernomordik, L.V.; Lebleu, B. Cell-penetrating Peptides. J. Biol. Chem., 2003, 278(1), 585-590.
[http://dx.doi.org/10.1074/jbc.M209548200] [PMID: 12411431]
[72]
Ter-Avetisyan, G.; Tünnemann, G.; Nowak, D.; Nitschke, M.; Herrmann, A.; Drab, M.; Cardoso, M.C. Cell entry of arginine-rich peptides is independent of endocytosis. J. Biol. Chem., 2009, 284(6), 3370-3378.
[http://dx.doi.org/10.1074/jbc.M805550200] [PMID: 19047062]
[73]
Tali, C. Scavenger receptors as a target for nucleic acid delivery with peptide vectors. University of Tarita Press; Tartu University, 2017.
[74]
Palade, G.E. fine structure of blood capillaries. J. Appl. Phys., 1953, 24, 1424.
[75]
Yamada, E. The fine structure of the renal glomerulus of the mouse. J. Cell Biol., 1955, 1(6), 551-566.
[http://dx.doi.org/10.1083/jcb.1.6.551] [PMID: 13278366]
[76]
Lamaze, C.; Dujeancourt, A.; Baba, T.; Lo, C.G.; Benmerah, A.; Dautry-Varsat, A. Interleukin 2 receptors and detergent-resistant membrane domains define a clathrin-independent endocytic pathway. Mol. Cell, 2001, 7(3), 661-671.
[http://dx.doi.org/10.1016/S1097-2765(01)00212-X] [PMID: 11463390]
[77]
Conner, S.D.; Schmid, S.L. Regulated portals of entry into the cell. Nature, 2003, 422(6927), 37-44.
[http://dx.doi.org/10.1038/nature01451] [PMID: 12621426]
[78]
Pujals, S.; Giralt, E. Proline-rich, amphipathic cell-penetrating peptides. Adv. Drug Deliv. Rev., 2008, 60(4-5), 473-484.
[http://dx.doi.org/10.1016/j.addr.2007.09.012] [PMID: 18187229]
[79]
Veldhoen, S.; Laufer, S.D.; Trampe, A.; Restle, T. Cellular delivery of small interfering RNA by a non-covalently attached cell-penetrating peptide: quantitative analysis of uptake and biological effect. Nucleic Acids Res., 2006, 34(22), 6561-6573.
[http://dx.doi.org/10.1093/nar/gkl941] [PMID: 17135188]
[80]
Abes, S.; Turner, J.J. lvanova G.D.; D. OwenD.; Williams D.; Arzumanov A.; ClairP. Gait M.J. and Lebleu B. Nucleic Acids Res., 2007, 35, 4495-4502.
[http://dx.doi.org/10.1093/nar/gkm418] [PMID: 17584792]
[81]
Eguchi, A.; Meade, B.R.; Chang, Y.C.; Fredrickson, C.T.; Willert, K.; Puri, N.; Dowdy, S.F. Efficient siRNA delivery into primary cells by a peptide transduction domain-dsRNA binding domain fusion protein. Nat. Biotechnol., 2009, 27(6), 567-571.
[http://dx.doi.org/10.1038/nbt.1541] [PMID: 19448630]
[82]
EL Andaloussi, S.; Lehto, T.; Mäger, I.; Rosenthal-Aizman, K.; Oprea, I.I.; Simonson, O.E.; Sork, H.; Ezzat, K.; Copolovici, D.M.; Kurrikoff, K.; Viola, J.R.; Zaghloul, E.M.; Sillard, R.; Johansson, H.J.; Said Hassane, F.; Guterstam, P.; Suhorutšenko, J.; Moreno, P.M.D.; Oskolkov, N.; Hälldin, J.; Tedebark, U.; Metspalu, A.; Lebleu, B.; Lehtiö, J.; Smith, C.I.E.; Langel, Ü. Design of a peptide-based vector, PepFect6, for efficient delivery of siRNA in cell culture and systemically in vivo. Nucleic Acids Res., 2011, 39(9), 3972-3987.
[http://dx.doi.org/10.1093/nar/gkq1299] [PMID: 21245043]
[83]
Mohandessi, S.; Rajendran, M.; Magda, D.; Miller, L.W. Cell-penetrating peptides as delivery vehicles for a protein-targeted terbium complex. Chemistry, 2012, 18(35), 10825-10829.
[http://dx.doi.org/10.1002/chem.201201805] [PMID: 22807190]
[84]
Hu, M.; Wang, J.; Chen, P.; Reilly, R.M. HIV-1 Tat peptide immunoconjugates differentially sensitize breast cancer cells to selected antiproliferative agents that induce the cyclin-dependent kinase inhibitor p21WAF-1/CIP-1. Bioconjug. Chem., 2006, 17(5), 1280-1287.
[http://dx.doi.org/10.1021/bc060053r] [PMID: 16984139]
[85]
Zou, L.L.; Ma, J.L.; Wang, T.; Yang, T.B.; Liu, C.B. Cell-penetrating Peptide-mediated therapeutic molecule delivery into the central nervous system. Curr. Neuropharmacol., 2013, 11(2), 197-208.
[http://dx.doi.org/10.2174/1570159X11311020006] [PMID: 23997754]
[86]
Kirschberg, T.A.; VanDeusen, C.L.; Rothbard, J.B.; Yang, M.; Wender, P.A. Arginine-based molecular transporters: the synthesis and chemical evaluation of releasable taxol-transporter conjugates. Org. Lett., 2003, 5(19), 3459-3462.
[http://dx.doi.org/10.1021/ol035234c] [PMID: 12967299]
[87]
Rothbard, J.B.; Garlington, S.; Lin, Q.; Kirschberg, T.; Kreider, E.; McGrane, P.L.; Wender, P.A.; Khavari, P.A. Conjugation of arginine oligomers to cyclosporin A facilitates topical delivery and inhibition of inflammation. Nat. Med., 2000, 6(11), 1253-1257.
[http://dx.doi.org/10.1038/81359] [PMID: 11062537]
[88]
Uhl, P.; Grundmann, C.; Sauter, M.; Storck, P.; Tursch, A.; Özbek, S.; Leotta, K.; Roth, R.; Witzigmann, D.; Kulkarni, J.A.; Fidelj, V.; Kleist, C.; Cullis, P.R.; Fricker, G.; Mier, W. Coating of PLA-nanoparticles with cyclic, arginine-rich cell penetrating peptides enables oral delivery of liraglutide. Nanomedicine, 2020, 24, 102132.
[http://dx.doi.org/10.1016/j.nano.2019.102132] [PMID: 31783138]
[89]
Santra, S.; Yang, H.; Dutta, D.; Stanley, J.T.; Holloway, P.H.; Tan, W.; Moudgil, B.M.; Mericle, R.A. TAT conjugated, FITC doped silica nanoparticles for bioimaging applications. Chem. Commun., 2004, 24(24), 2810-2811.
[http://dx.doi.org/10.1039/b411916a] [PMID: 15599418]
[90]
Santra, S.; Yang, H.; Stanley, J.T.; Holloway, P.H.; Moudgil, B.M.; Walter, G.; Mericle, R.A. Rapid and effective labeling of brain tissue using TAT-conjugated CdS : Mn/ZnS quantum dots. Chem. Commun., 2005, (25), 3144-3146.
[http://dx.doi.org/10.1039/b503234b] [PMID: 15968352]
[91]
Sabaghzadeh, S.; Sadat, S.M.; Rohollah, F.; Bolhassani, A. Effective delivery of Nef-MPER-V3 fusion protein using ldp12 cell penetrating peptide for development of preventive/therapeutic HIV-1 vaccine. Protein Pept. Lett., 2020, 27(11), 1151-1158.
[http://dx.doi.org/10.2174/0929866527666200504121400] [PMID: 32364062]
[92]
Seesuay, W.; Phanthong, S.; Densumite, J.; Mahasongkram, K.; Sookrung, N.; Chaicumpa, W. Human transbodies to reverse transcriptase connection subdomain of hiv-1 gag-pol polyprotein reduce infectiousness of the virus progeny. Vaccines, 2021, 9(8), 893.
[http://dx.doi.org/10.3390/vaccines9080893] [PMID: 34452018]
[93]
Good, L.; Awasthi, S.K.; Dryselius, R.; Larsson, O.; Nielsen, P.E. Bactericidal antisense effects of peptide-PNA conjugates. Nat. Biotechnol., 2001, 19(4), 360-364.
[http://dx.doi.org/10.1038/86753] [PMID: 11283595]
[94]
Deshayes, S.; Konate, K.; Aldrian, G.; Cromben, L.; Heitz, F.; Divita, G. Structural polymorphism of non-covalent peptide based delivery systems: highways to cellular uptake. Biochim. Biophys. Acta, 1798, 2010, 2304-2314.
[95]
Tan, X.X.; Actor, J.K.; Chen, Y. Peptide nucleic acid antisense oligomer as a therapeutic strategy against bacterial infection: proof of principle using mouse intraperitoneal infection. Antimicrob. Agents Chemother., 2005, 49(8), 3203-3207.
[http://dx.doi.org/10.1128/AAC.49.8.3203-3207.2005] [PMID: 16048926]
[96]
Gao, S.; Tian, B.; Han, J.; Zhang, J.; Shi, Y.; Lv, Q.; Li, K. Enhanced transdermal delivery of lornoxicam by nanostructured lipid carrier gels modified with polyarginine peptide for treatment of carrageenan-induced rat paw edema. Int. J. Nanomedicine, 2019, 14, 6135-6150.
[http://dx.doi.org/10.2147/IJN.S205295] [PMID: 31447556]
[97]
Jeong, E.J.; Choi, M.; Lee, J.; Rhim, T.; Lee, K.Y. The spacer arm length in cell-penetrating peptides influences chitosan/siRNA nanoparticle delivery for pulmonary inflammation treatment. Nanoscale, 2015, 7(47), 20095-20104.
[http://dx.doi.org/10.1039/C5NR06903C] [PMID: 26568525]
[98]
Kim, J.Y.; Ahn, J.; Kim, J.; Choi, M.; Jeon, H.; Choe, K.; Lee, D.Y.; Kim, P.; Jon, S. Nanoparticle-assisted transcutaneous delivery of a signal transducer and activator of transcription 3-inhibiting peptide ameliorates psoriasis-like skin inflammation. ACS Nano, 2018, 12(7), 6904-6916.
[http://dx.doi.org/10.1021/acsnano.8b02330] [PMID: 29949348]
[99]
Sharma, G.; Lakkadwala, S.; Modgil, A.; Singh, J. The role of cell-penetrating peptide and transferrin on enhanced delivery of drug to brain. Int. J. Mol. Sci., 2016, 17(6), 806.
[http://dx.doi.org/10.3390/ijms17060806] [PMID: 27231900]
[100]
Young, C.K.; Minuk, S.; Sora, K. Cell-penetrating artificial mitochondria-targeting peptide-conjugate dmetallothionein 1a alleviates mitochondrial damage in parkinson’s disease model. Exp. Mol. Med., 2018, 50(8), 1-13.
[http://dx.doi.org/10.1038/s12276-018-0124-z]
[101]
Kristen, M.A.; Geoffrey, L.C.; Jen’s, T.R.; Samuel, C.G.; Gobinda, S.; Jenkins, R.B.; Subramanian, R.; Josheph, F.P.; Karunga, K.K. Cationic carrier peptide enhances cerebrovascular targeting of nanoparticles in Alzheimer’s disease brain. Nanomedicine, 2019, 16, 258-266. ISSN 1549-9634
[http://dx.doi.org/10.1016/j.nano.2018.09.010]
[102]
Maderna, E.; Colombo, L.; Cagnotto, A.; Di Fede, G.; Indaco, A.; Tagliavini, F.; Salmona, M.; Giaccone, G. In situ tissue labeling of cerebral amyloid using hiv-related tat peptide. Mol. Neurobiol., 2018, 55(8), 6834-6840.
[http://dx.doi.org/10.1007/s12035-018-0870-x] [PMID: 29349578]
[103]
Liu, C.; Tai, L.; Zhang, W.; Wei, G.; Pan, W.; Lu, W. Penetratin, a potentially powerful absorption enhancer for noninvasive intraocular drug delivery. Mol. Pharm., 2014, 11(4), 1218-1227.
[http://dx.doi.org/10.1021/mp400681n] [PMID: 24521351]
[104]
Liang, J.F.; Yang, V.C. Insulin-cell penetrating peptide hybrids with improved intestinal absorption efficiency. Biochem. Biophys. Res. Commun., 2005, 335(3), 734-738.
[http://dx.doi.org/10.1016/j.bbrc.2005.07.142] [PMID: 16115469]
[105]
Kristensen, M.; Franzyk, H.; Klausen, M.T.; Iversen, A.; Bahnsen, J.S.; Skyggebjerg, R.B.; Foderà, V.; Nielsen, H.M. Penetratin-mediated transepithelial insulin permeation: Importance of cationic residues and pH for complexation and permeation. AAPS J., 2015, 17(5), 1200-1209.
[http://dx.doi.org/10.1208/s12248-015-9747-3] [PMID: 25990963]
[106]
Alves, I.D.; Carré, M.; Montero, M.P.; Castano, S.; Lecomte, S.; Marquant, R.; Lecorché, P.; Burlina, F.; Schatz, C.; Sagan, S.; Chassaing, G.; Braguer, D.; Lavielle, S. A proapoptotic peptide conjugated to penetratin selectively inhibits tumor cell growth. Biochim. Biophys. Acta Biomembr., 2014, 1838(8), 2087-2098.
[http://dx.doi.org/10.1016/j.bbamem.2014.04.025] [PMID: 24796502]
[107]
Liu, Y.; Song, Z.; Zheng, N.; Nagasaka, K.; Yin, L.; Cheng, J. Systemic siRNA delivery to tumors by cell-penetrating α-helical polypeptide-based metastable nanoparticles. Nanoscale, 2018, 10(32), 15339-15349.
[http://dx.doi.org/10.1039/C8NR03976C] [PMID: 30070662]
[108]
Srimanee, A.; Arvanitidou, M.; Kim, K.; Hällbrink, M.; Langel, Ü. Cell-penetrating peptides for siRNA delivery to glioblastomas. Peptides, 2018, 104, 62-69.
[http://dx.doi.org/10.1016/j.peptides.2018.04.015] [PMID: 29684592]
[109]
Tetley, G.J.N.; Murphy, N.P.; Bonetto, S.; Ivanova-Berndt, G.; Revell, J.; Mott, H.R.; Cooley, R.N.; Owen, D. The discovery and maturation of peptide biologics targeting the small G-protein Cdc42: A bioblockade for Ras-driven signaling. J. Biol. Chem., 2020, 295(9), 2866-2884.
[http://dx.doi.org/10.1074/jbc.RA119.010077] [PMID: 31959628]
[110]
Yang, W.; Xia, Y.; Fang, Y.; Meng, F.; Zhang, J.; Cheng, R.; Deng, C.; Zhong, Z. Selective cell penetrating peptide-functionalized polymersomes mediate efficient and targeted delivery of methotrexate disodium to human lung cancer in vivo. Adv. Healthc. Mater., 2018, 7(7), 1701135.
[http://dx.doi.org/10.1002/adhm.201701135] [PMID: 29280317]
[111]
Szabó, I.; Orbán, E.; Schlosser, G.; Hudecz, F.; Bánóczi, Z. Cell-penetrating conjugates of pentaglutamylated methotrexate as potential anticancer drugs against resistant tumor cells. Eur. J. Med. Chem., 2016, 115, 361-368.
[http://dx.doi.org/10.1016/j.ejmech.2016.03.034] [PMID: 27031212]
[112]
Kim, S.M.; Chae, M.K.; Lee, C.; Yim, M.S.; Bang, J.K.; Ryu, E.K. Enhanced cellular uptake of a TAT-conjugated peptide inhibitor targeting the polo-box domain of polo-like kinase 1. Amino Acids, 2014, 46(11), 2595-2603.
[http://dx.doi.org/10.1007/s00726-014-1798-8] [PMID: 25151148]
[113]
Duan, Z.; Chen, C.; Qin, J.; Liu, Q.; Wang, Q.; Xu, X.; Wang, J. Cell-penetrating peptide conjugates to enhance the antitumor effect of paclitaxel on drug-resistant lung cancer. Drug Deliv., 2017, 24(1), 752-764.
[http://dx.doi.org/10.1080/10717544.2017.1321060] [PMID: 28468542]
[114]
Li, Y.; Zheng, X.; Cao, Z.; Xu, W.; Zhang, J.; Gong, M. Self-assembled peptide (CADY-1) improved the clinical application of doxorubicin. Int. J. Pharm., 2012, 434(1-2), 209-214.
[http://dx.doi.org/10.1016/j.ijpharm.2012.06.003] [PMID: 22688249]
[115]
Cheng, H.; Zhu, J.Y.; Xu, X.D.; Qiu, W.X.; Lei, Q.; Han, K.; Cheng, Y.J.; Zhang, X.Z. Activable cell-penetrating peptide conjugated prodrug for tumor targeted drug delivery. ACS Appl. Mater. Interfaces, 2015, 7(29), 16061-16069.
[http://dx.doi.org/10.1021/acsami.5b04517] [PMID: 26161578]
[116]
Darwish, S.; Sadeghiani, N.; Fong, S.; Mozaffari, S.; Hamidi, P.; Withana, T.; Yang, S.; Tiwari, R.K.; Parang, K. Synthesis and antiproliferative activities of doxorubicin thiol conjugates and doxorubicin-SS-cyclic peptide. Eur. J. Med. Chem., 2019, 161, 594-606.
[http://dx.doi.org/10.1016/j.ejmech.2018.10.042] [PMID: 30396106]
[117]
Dougherty, P.G.; Wen, J.; Pan, X.; Koley, A.; Ren, J.G.; Sahni, A.; Basu, R.; Salim, H.; Appiah Kubi, G.; Qian, Z.; Pei, D. Enhancing the cell permeability of stapled peptides with a cyclic cell-penetrating peptide. J. Med. Chem., 2019, 62(22), 10098-10107.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00456] [PMID: 31657556]
[118]
Fields, G.B. Ed. Methods in Enzymology, Solid-phase peptide Synthesis; Academic Press: new York, 1997, Vol. 289, pp. 3-780.
[119]
White, P.D.; Chan, W.C. Basic Principles. In: Fmoc solid phase peptide Synthesis: A Practical Approach; Oxford University Press: Oxford, 2000. chap. 2.

[120]
Jornada, D.; dos Santos Fernandes, G.; Chiba, D.; de Melo, T.; dos Santos, J.; Chung, M. The prodrug approach: a successful tool for improving drug solubility. Molecules, 2015, 21(1), 42.
[http://dx.doi.org/10.3390/molecules21010042] [PMID: 28036069]
[121]
Nasrolahi Shirazi, A.; Tiwari, R.; Chhikara, B.S.; Mandal, D.; Parang, K. Design and biological evaluation of cell-penetrating peptide-doxorubicin conjugates as prodrugs. Mol. Pharm., 2013, 10(2), 488-499.
[http://dx.doi.org/10.1021/mp3004034] [PMID: 23301519]
[122]
Lelle, M.; Frick, S.U.; Steinbrink, K.; Peneva, K. Novel cleavable cell-penetrating peptide-drug conjugates: synthesis and characterization. J. Pept. Sci., 2014, 20(5), 323-333.
[http://dx.doi.org/10.1002/psc.2617] [PMID: 24677287]
[123]
Shi, N.Q.; Gao, W.; Xiang, B.; Qi, X.R. Enhancing cellular uptake of activable cell-penetrating peptide-doxorubicin conjugate by enzymatic cleavage. Int. J. Nanomedicine, 2012, 7, 1613-1621.
[PMID: 22619516]
[124]
Prater, C.E.; Miller, P.S. 3'-methylphosphonate-modified oligo-2'-O-methylribonucleotides and their Tat peptide conjugates: uptake and stability in mouse fibroblasts in culture. Bioconjug. Chem., 2004, 15(3), 498-507.
[http://dx.doi.org/10.1021/bc049977+] [PMID: 15149177]
[125]
Akishiba, M.; Takeuchi, T.; Kawaguchi, Y.; Sakamoto, K.; Yu, H.H.; Nakase, I.; Takatani-Nakase, T.; Madani, F.; Gräslund, A.; Futaki, S. Cytosolic antibody delivery by lipid-sensitive endosomolytic peptide. Nat. Chem., 2017, 9(8), 751-761.
[http://dx.doi.org/10.1038/nchem.2779] [PMID: 28754944]
[126]
Sakamoto, K.; Akishiba, M.; Iwata, T.; Murata, K.; Mizuno, S.; Kawano, K.; Imanishi, M.; Sugiyama, F.; Futaki, S. Optimizing charge switching in membrane lytic peptides for endosomal release of biomacromolecules. Angew. Chem. Int. Ed., 2020, 59(45), 19990-19998.
[http://dx.doi.org/10.1002/anie.202005887] [PMID: 32557993]
[127]
Li, W.; Nicol, F.; Szoka, F.C. Jr GALA: a designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery. Adv. Drug Deliv. Rev., 2004, 56(7), 967-985.
[http://dx.doi.org/10.1016/j.addr.2003.10.041] [PMID: 15066755]
[128]
Xiao, Q.; Du, W.; Dong, X.; Du, S.; Ong, S.Y.; Tang, G.; Zhang, C.; Yang, F.; Li, L.; Gao, L.; Yao, S.Q. Cell-penetrating mitochondrion-targeting ligands for the universal delivery of small molecules, proteins and nanomaterials. Chemistry, 2021, 27(47), 12207-12214.
[http://dx.doi.org/10.1002/chem.202101989] [PMID: 34115398]
[129]
Xiao, Q.; Dong, X.; Yang, F.; Zhou, S.; Xiang, M.; Lou, L.; Yao, S.Q.; Gao, L. Engineered Cell-Penetrating Peptides for Mitochondrion-Targeted Drug Delivery in Cancer Therapy. Chemistry, 2021, 27(59), 14721-14729.
[http://dx.doi.org/10.1002/chem.202102523] [PMID: 34436802]
[130]
Deng, X.; Mai, R.; Zhang, C.; Yu, D.; Ren, Y.; Li, G.; Cheng, B.; Li, L.; Yu, Z.; Chen, J. Discovery of novel cell-penetrating and tumor-targeting peptide-drug conjugate (PDC) for programmable delivery of paclitaxel and cancer treatment. Eur. J. Med. Chem., 2021, 213, 113050.
[http://dx.doi.org/10.1016/j.ejmech.2020.113050] [PMID: 33280896]
[131]
Yurko, R.; Islam, K.; Weber, B.; Salama, G.; Zahid, M. Conjugation of Amiodarone to a Novel Cardiomyocyte Targeting Peptide for Potential Targeted Delivery to the Heart. Res Sq. preprint, 2023. (version 1).
[http://dx.doi.org/10.21203/rs.3.rs-2436601/v1]
[132]
Jauset, T.; Beaulieu, M.E. Bioactive cell penetrating peptides and proteins in cancer: a bright future ahead. Curr. Opin. Pharmacol., 2019, 47, 133-140.
[http://dx.doi.org/10.1016/j.coph.2019.03.014] [PMID: 31048179]
[133]
Erazo-Oliveras, A.; Muthukrishnan, N.; Baker, R.; Wang, T.Y.; Pellois, J.P. Improving the endosomal escape of cell-penetrating peptides and their cargos: strategies and challenges. Pharmaceuticals, 2012, 5(11), 1177-1209.
[http://dx.doi.org/10.3390/ph5111177] [PMID: 24223492]
[134]
Moutal, A.; François-Moutal, L.; Brittain, J.M.; Khanna, M.; Khanna, R. Differential neuroprotective potential of CRMP2 peptide aptamers conjugated to cationic, hydrophobic, and amphipathic cell penetrating peptides. Front. Cell. Neurosci., 2015, 8, 471.
[http://dx.doi.org/10.3389/fncel.2014.00471] [PMID: 25674050]
[135]
Walrant, A.; Cardon, S.; Burlina, F.; Sagan, S. Membrane crossing and Membranotropic activity of cell-penetrating peptides: dangerous liaisons? Acc. Chem. Res., 2017, 50(12), 2968-2975.
[http://dx.doi.org/10.1021/acs.accounts.7b00455] [PMID: 29172443]
[136]
Miampamba, M.; Liu, J.; Harootunian, A.; Gale, A.J.; Baird, S.; Chen, S.L.; Nguyen, Q.T.; Tsien, R.Y.; González, J.E. Sensitive in vivo Visualization of Breast Cancer Using Ratiometric Protease-activatable Fluorescent Imaging Agent, AVB-620. Theranostics, 2017, 7(13), 3369-3386.
[http://dx.doi.org/10.7150/thno.20678] [PMID: 28900516]
[137]
Coriat, R.; Faivre, S.; Mir, O.; Dreyer, C.; Ropert, S.; Bouattour, M.; Desjardins, R.; Goldwasser, F.; Raymond, E. Pharmacokinetics and safety of DTS-108, a human oligopeptide bound to SN-38 with an esterase-sensitive cross-linker in patients with advanced malignancies: a Phase I study. Int. J. Nanomedicine, 2016, 11, 6207-6216.
[http://dx.doi.org/10.2147/IJN.S110274] [PMID: 27920527]
[138]
Christopher, C.; Florent, A.; Catherine, C.G.; Jean, P.B.; Laurent, K.; Pascale, M.; Catherine, D.; Julien, P. Postoperative ocular inflammation; A Single subconjunctival injection of XG-102 compared to dexamethasone drops in a randomized trial. Am. J. Ophthalmol., 2017, 174, 76-84.
[http://dx.doi.org/10.1016/j.ajo.2016.10.012] [PMID: 27810317]
[139]
U. S. National Library of Medicine https://clinicaltrials.gov/ct2/show/NCT00914914 (Accessed on 3rdMay 2022).
[140]
Lulla, R.R.; Goldman, S.; Yamada, T.; Beattie, C.W.; Bressler, L.; Pacini, M.; Pollack, I.F.; Fisher, P.G.; Packer, R.J.; Dunkel, I.J.; Dhall, G.; Wu, S.; Onar, A.; Boyett, J.M.; Fouladi, M. Phase I trial of p28 (NSC745104), a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in pediatric patients with recurrent or progressive central nervous system tumors: A Pediatric Brain Tumor Consortium Study. Neuro-oncol., 2016, 18(9), 1319-1325.
[http://dx.doi.org/10.1093/neuonc/now047] [PMID: 27022131]
[141]
Capron, M.; Béghin, L.; Leclercq, C.; Labreuche, J.; Dendooven, A.; Standaert, A.; Delbeke, M.; Porcherie, A.; Nachury, M.; Boruchowicz, A.; Dupas, J.L.; Fumery, M.; Paupard, T.; Catteau, S.; Deplanque, D.; Colombel, J.F.; Desreumaux, P. Safety of P28GST, a protein derived from a schistosome helminth parasite, in patients with crohn’s disease: A pilot study (ACROHNEM). J. Clin. Med., 2019, 9(1), 41.
[http://dx.doi.org/10.3390/jcm9010041] [PMID: 31878146]
[142]
Staecker, H.; Jokovic, G.; Karpishchenko, S.; Kienle-Gogolok, A.; Krzyzaniak, A.; Lin, C.D.; Navratil, P.; Tzvetkov, V.; Wright, N.; Meyer, T. Efficacy and safety of AM-111 in the treatment of acute unilateral sudden deafness—a double-blind, randomized, placebo-controlled phase 3 study. Otol. Neurotol., 2019, 40(5), 584-594.
[http://dx.doi.org/10.1097/MAO.0000000000002229] [PMID: 31083077]
[143]
Bookmark, G. Peptide compound cyclization method., Patent WO2003106491A2, 2003.
[144]
Gilles, D.; Frederic, H.; Catherine, M.; Gudrun, A.H. Cell penetrating peptides for intracellular delivery of molecules., Patent US20070129305A1,
[145]
Mattias, H.; Margus, P.; Madis, M.; Priit, K.; Andreas, V.; Anne, M.; Maria, L.; Gräslund, A. Cell penetrating peptides., Patent WO2003106491A3, 2003.
[146]
Foster, K. Improvements in drug delivery., Patent GB2574525A, 2020.
[147]
Dehua, P.; Ziqing, Q. Polypeptide conjugates for intracellular delivery of sta- pled peptides. Patent EP3700548A4, 2020.
[148]
Matthew, W.; Suzan, H.; Melissa, B.; Michael, G.; Frank, A.; McClorey, G. Cell penetrating peptides US patent: 20220041662, 2022.
[149]
Ulrich, B.; Alexander, H.; Daniela, M. Cell penetrating peptides and uses thereof., Patent US20130164219A1, 2013.
[150]
Langel, Ü. Classes and Applications of Cell-Penetrating Peptides; CPP, Cell-Penetrating Peptides, 2019, pp. 29-82.
[http://dx.doi.org/10.1007/978- 981-13-8747-0_2]
[151]
https://www.sciencefacts.net/endocytosis.html (Accessed on 13th April 2022)

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