Abstract
Cell-penetrating peptides (CPPs) have been widely explored as an effective tool to deliver a variety of molecules and nanoparticles into cells due to their intrinsic property to translocate across cell membranes. CPPs are easier to synthesize and functionalize, and their incorporation into delivery vehicles could be achieved by both non-covalent and covalent methods. Recent advances in molecular self-assembly have demonstrated the possibility to fabricate various nanostructures with precise control over the shape, size and presentation of diverse functionalities. Through rational design, CPPs could be used as a building block for the nanostructure formation via self-assembly, while providing the functionality for intracellular delivery. In this book chapter, we will describe strategies to design self-assembling CPP conjugates and illustrate how their self-assembled nanostructures are manipulated for effective intracellular delivery. Fundamental knowledge on CPPs and molecular self-assembly will also be described.
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References
Bode SA, Thevenin M, Bechara C, Sagan S, Bregant S, Lavielle S, Chassaing G, Burlina F (2012) Self-assembling mini cell-penetrating peptides enter by both direct translocation and glycosaminoglycan-dependent endocytosis. Chem Commun 48(57):7179–7181. https://doi.org/10.1039/c2cc33240j
Chaloin L, Vidal P, Lory P, Mery J, Lautredou N, Divita G, Heitz F (1998) Design of carrier peptide-oligonucleotide conjugates with rapid membrane translocation and nuclear localization properties. Biochem Biophys Res Commun 243(2):601–608. https://doi.org/10.1006/bbrc.1997.8050
Chen JX, Xu XD, Chen WH, Zhang XZ (2014) Multi-functional envelope-type nanoparticles assembled from amphiphilic peptidic prodrug with improved anti-tumor activity. ACS Appl Mater Interfaces 6(1):593–598. https://doi.org/10.1021/am404680n
Copolovici DM, Langel K, Eriste E, Langel U (2014) Cell-penetrating peptides: design, synthesis, and applications.ACS. Nano 8(3):1972–1994. https://doi.org/10.1021/nn4057269
Crombez L, Aldrian-Herrada G, Konate K, Nguyen QN, McMaster GK, Brasseur R, Heitz F, Divita G (2009) A new potent secondary amphipathic cell-penetrating peptide for siRNA delivery into mammalian cells. Mol Ther 17(1):95–103. https://doi.org/10.1038/mt.2008.215
Cui H, Webber MJ, Stupp SI (2010) Self-assembly of peptide amphiphiles: from molecules to nanostructures to biomaterials. Biopolymers 94(1):1–18. https://doi.org/10.1002/bip.21328
Derossi D, Joliot AH, Chassaing G, Prochiantz A (1994) The third helix of the Antennapedia homeodomain translocates through biological membranes. J Biol Chem 269(14):10444–10450
Farkhani SM, Valizadeh A, Karami H, Mohammadi S, Sohrabi N, Badrzadeh F (2014) Cell penetrating peptides: efficient vectors for delivery of nanoparticles, nanocarriers, therapeutic and diagnostic molecules. Peptides 57:78–94. https://doi.org/10.1016/j.peptides.2014.04.015
Fonseca SB, Pereira MP, Kelley SO (2009) Recent advances in the use of cell-penetrating peptides for medical and biological applications. Adv Drug Deliv Rev 61(11):953–964. https://doi.org/10.1016/j.addr.2009.06.001
Frankel AD, Pabo CO (1988) Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55(6):1189–1193
Futaki S, Suzuki T, Ohashi W, Yagami T, Tanaka S, Ueda K, Sugiura Y (2001) Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J Biol Chem 276(8):5836–5840. https://doi.org/10.1074/jbc.M007540200
Green M, Loewenstein PM (1988) Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell 55(6):1179–1188
Habibi N, Kamaly N, Memic A, Shafiee H (2016) Self-assembled peptide-based nanostructures: smart nanomaterials toward targeted drug delivery. Nano Today 11(1):41–60. https://doi.org/10.1016/j.nantod.2016.02.004
Holowka EP, Sun VZ, Kamei DT, Deming TJ (2007) Polyarginine segments in block copolypeptides drive both vesicular assembly and intracellular delivery. Nat Mater 6(1):52–57. https://doi.org/10.1038/nmat1794
Juliano RL, Alam R, Dixit V, Kang HM (2009) Cell-targeting and cell-penetrating peptides for delivery of therapeutic and imaging agents. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1(3):324–335. https://doi.org/10.1002/wnan.4
Kanazawa T, Taki H, Tanaka K, Takashima Y, Okada H (2011) Cell-penetrating peptide-modified block copolymer micelles promote direct brain delivery via intranasal administration. Pharm Res 28(9):2130–2139. https://doi.org/10.1007/s11095-011-0440-7
Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W (2004) Reversal of obesity by targeted ablation of adipose tissue. Nat Med 10(6):625–632
Koren E, Torchilin VP (2012) Cell-penetrating peptides: breaking through to the other side. Trends Mol Med 18(7):385–393. https://doi.org/10.1016/j.molmed.2012.04.012
Lim YB, Lee E, Lee M (2007a) Cell-penetrating-peptide-coated nanoribbons for intracellular nanocarriers. Angew Chem 46(19):3475–3478. https://doi.org/10.1002/anie.200604576
Lim YB, Lee E, Lee M (2007b) Controlled bioactive nanostructures from self-assembly of peptide building blocks. Angew Chem 46(47):9011–9014. https://doi.org/10.1002/anie.200702732
Lim YB, Moon KS, Lee M (2009) Recent advances in functional supramolecular nanostructures assembled from bioactive building blocks. Chem Soc Rev 38(4):925–934. https://doi.org/10.1039/b809741k
Liu L, Xu K, Wang H, Tan PK, Fan W, Venkatraman SS, Li L, Yang YY (2009) Self-assembled cationic peptide nanoparticles as an efficient antimicrobial agent. Nat Nanotechnol 4(7):457–463. https://doi.org/10.1038/nnano.2009.153
Lock LL, Cheetham AG, Zhang P, Cui H (2013) Design and construction of supramolecular nanobeacons for enzyme detection. ACS Nano 7(6):4924–4932. https://doi.org/10.1021/nn400218a
Macewan SR, Chilkoti A (2012) Digital switching of local arginine density in a genetically encoded self-assembled polypeptide nanoparticle controls cellular uptake. Nano Lett 12(6):3322–3328. https://doi.org/10.1021/nl301529p
MacEwan SR, Chilkoti A (2013) Harnessing the power of cell-penetrating peptides: activatable carriers for targeting systemic delivery of cancer therapeutics and imaging agents. Wiley Interdiscip Rev Nanomed Nanobiotechnol 5(1):31–48. https://doi.org/10.1002/wnan.1197
MacEwan SR, Chilkoti A (2014) Controlled apoptosis by a thermally toggled nanoscale amplifier of cellular uptake. Nano Lett 14(4):2058–2064. https://doi.org/10.1021/nl5002313
Mae M, Langel U (2006) Cell-penetrating peptides as vectors for peptide, protein and oligonucleotide delivery. Curr Opin Pharmacol 6(5):509–514. https://doi.org/10.1016/j.coph.2006.04.004
Mendes AC, Baran ET, Reis RL, Azevedo HS (2013) Self-assembly in nature: using the principles of nature to create complex nanobiomaterials. Wiley Interdiscip Rev Nanomed Nanobiotechnol 5(6):582–612. https://doi.org/10.1002/wnan.1238
Milletti F (2012) Cell-penetrating peptides: classes, origin, and current landscape. Drug Discov Today 17(15-16):850–860. https://doi.org/10.1016/j.drudis.2012.03.002
Nakase I, Akita H, Kogure K, Graslund A, Langel U, Harashima H, Futaki S (2012) Efficient intracellular delivery of nucleic acid pharmaceuticals using cell-penetrating peptides. Acc Chem Res 45(7):1132–1139. https://doi.org/10.1021/ar200256e
Oehlke J, Scheller A, Wiesner B, Krause E, Beyermann M, Klauschenz E, Melzig M, Bienert M (1998) Cellular uptake of an alpha-helical amphipathic model peptide with the potential to deliver polar compounds into the cell interior non-endocytically. Biochim Biophys Acta 1414(1-2):127–139
Pooga M, Hallbrink M, Zorko M, Langel U (1998) Cell penetration by transportan. FASEB J 12(1):67–77
Raucher D, Ryu JS (2015) Cell-penetrating peptides: strategies for anticancer treatment. Trends Mol Med 21(9):560–570. https://doi.org/10.1016/j.molmed.2015.06.005
Reissmann S (2014) Cell penetration: scope and limitations by the application of cell-penetrating peptides. J Pept Sci 20(10):760–784. https://doi.org/10.1002/psc.2672
Saalik P, Elmquist A, Hansen M, Padari K, Saar K, Viht K, Langel U, Pooga M (2004) Protein cargo delivery properties of cell-penetrating peptides. A comparative study. Bioconjug Chem 15(6):1246–1253. https://doi.org/10.1021/bc049938y
Said Hassane F, Saleh AF, Abes R, Gait MJ, Lebleu B (2010) Cell penetrating peptides: overview and applications to the delivery of oligonucleotides. Cell Mol Life Sci 67(5):715–726. https://doi.org/10.1007/s00018-009-0186-0
Tian R, Wang H, Niu R, Ding D (2015) Drug delivery with nanospherical supramolecular cell penetrating peptide-taxol conjugates containing a high drug loading. J Colloid Interface Sci 453:15–20. https://doi.org/10.1016/j.jcis.2015.04.028
Toksöz S, Guler MO (2009) Self-assembled peptidic nanostructures. Nano Today 4(6):458–469
Torchilin VP (2014) Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery. Nat Rev Drug Discov 13(11):813–827. https://doi.org/10.1038/nrd4333
Tu Y, Zhu L (2015) Enhancing cancer targeting and anticancer activity by a stimulus-sensitive multifunctional polymer-drug conjugate. J Control Release 212:94–102. https://doi.org/10.1016/j.jconrel.2015.06.024
Tünnemann G, Ter-Avetisyan G, Martin RM, Stöckl M, Herrmann A, Cardoso MC (2008) Live-cell analysis of cell penetration ability and toxicity of oligo-arginines. J Pept Sci 14(4):469–476
Wang HY, Chen JX, Sun YX, Deng JZ, Li C, Zhang XZ, Zhuo RX (2011) Construction of cell penetrating peptide vectors with N-terminal stearylated nuclear localization signal for targeted delivery of DNA into the cell nuclei. J Control Release 155(1):26–33. https://doi.org/10.1016/j.jconrel.2010.12.009
Wang F, Wang Y, Zhang X, Zhang W, Guo S, Jin F (2014) Recent progress of cell-penetrating peptides as new carriers for intracellular cargo delivery. J Control Release 174:126–136. https://doi.org/10.1016/j.jconrel.2013.11.020
Won YW, Adhikary PP, Lim KS, Kim HJ, Kim JK, Kim YH (2014) Oligopeptide complex for targeted non-viral gene delivery to adipocytes. Nat Mat 13(12):1157–1164. https://doi.org/10.1038/nmat4092
Yoon YR, Lim YB, Lee E, Lee M (2008) Self-assembly of a peptide rod-coil: a polyproline rod and a cell-penetrating peptide tat coil. Chem Commun 16:1892–1894. https://doi.org/10.1039/b719868j
Zhang P, Cheetham AG, Lin YA, Cui H (2013) Self-assembled Tat nanofibers as effective drug carrier and transporter. ACS Nano 7(7):5965–5977. https://doi.org/10.1021/nn401667z
Zhang Q, Gao H, He Q (2015) Taming cell penetrating peptides: never too old to teach old dogs new tricks. Mol Pharm 12(9):3105–3118. https://doi.org/10.1021/acs.molpharmaceut.5b00428
Zhao XL, Chen BC, Han JC, Wei L, Pan XB (2015) Delivery of cell-penetrating peptide-peptide nucleic acid conjugates by assembly on an oligonucleotide scaffold. Sci Rep 5:17640. https://doi.org/10.1038/srep17640
Zhu X, Shan W, Zhang P, Jin Y, Guan S, Fan T, Yang Y, Zhou Z, Huang Y (2014) Penetratin derivative-based nanocomplexes for enhanced intestinal insulin delivery. Mol Pharm 11(1):317–328. https://doi.org/10.1021/mp400493b
Acknowledgments
Y. Shi thanks the China Scholarship Council for her PhD scholarship (No.201307060020) and J. Conde acknowledges Marie Curie International Outgoing Fellowship (FP7-PEOPLE-2013-IOF, Project No. 626386).
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Shi, Y., Conde, J., Azevedo, H.S. (2017). Empowering the Potential of Cell-Penetrating Peptides for Targeted Intracellular Delivery via Molecular Self-Assembly. In: Sunna, A., Care, A., Bergquist, P. (eds) Peptides and Peptide-based Biomaterials and their Biomedical Applications. Advances in Experimental Medicine and Biology, vol 1030. Springer, Cham. https://doi.org/10.1007/978-3-319-66095-0_12
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DOI: https://doi.org/10.1007/978-3-319-66095-0_12
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