Abstract
Recent research efforts have focused on the optimization of cell delivery systems with the aims of increasing cell specificity, incorporating organelle targeting and improving overall delivery efficiency. Peptides and proteins represent new and innovative strategies to meet these targets. The advantages of peptides are manyfold: they can condense DNA into compact particles for transport, disrupt the endosomal membrane, escape proteasomal degradation, traffic therapeutic molecules of various size, charge, and function to targeted intracellular compartments, and can have reduced cytotoxicity and immunogenicity. These properties can be part of a single peptide or the result from the conjugation of different peptides. Silk, a structural protein, is well known for its biodegradability and biocompatibility and can be tailored for specific design features via genetic engineering. With tunable structure, chemistry, and mechanical properties for silk proteins derived from spiders and insects, modified or recombinant silk proteins can be utilized in various biomedical applications such as for the design of gene delivery systems. This review summarizes the diversity and application of peptides and silk proteins to mediate intracellular delivery of genes and drugs.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Chakrabarti R, Wylie DE, Schuster SM (1989) Transfer of monoclonal antibodies into mammalian cells by electroporation. J Biol Chem 264:15494–15500
Arnheiter H, Haller O (1988) Antiviral state against influenza virus neutralized by microinjection of antibodies to interferon-induced Mx proteins. EMBO J 7:1315–1320
Glover DJ, Lipps HJ, Jans DA (2005) Towards safe, non-viral therapeutic gene expression in humans. Nat Rev Genet 6:299–310. doi:10.1038/nrg1577
Schwartz JJ, Zhang S (2000) Peptide-mediated cellular delivery. Curr Opin Mol Ther 2:162–167
Varga CM, Wickham TJ, Lauffenburger DA (2000) Receptor-mediated targeting of gene delivery vectors: insights from molecular mechanisms for improved vehicle design. Biotechnol Bioeng 70:593–605. doi:10.1002/1097-0290(20001220)70:6
Wadhwa MS, Collard WT, Adami RC, McKenzie DL, Rice KG (1997) Peptide-mediated gene delivery: influence of peptide structure on gene expression. Bioconjug Chem 8:81–88. doi:10.1021/bc960079q
Adami RC, Rice KG (1999) Metabolic stability of glutaraldehyde cross-linked peptide DNA condensates. J Pharm Sci 88:739–746. doi:10.1021/js990042p
Deshayes S, Morris MC, Divita G, Heitz F (2005) Cell-penetrating peptides: tools for intracellular delivery of therapeutics. Cell Mol Life Sci 62:1839–1849. doi:10.1007/s00018-005-5109-0
Gupta B, Levchenko TS, Torchilin VP (2005) Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. Adv Drug Deliv Rev 57:637–651. doi:10.1016/j.addr.2004.10.007
Kalderon D, Richardson WD, Markham AF, Smith AE (1984) Sequence requirements for nuclear location of simian virus 40 large-T antigen. Nature 311:33–38. doi:10.1038/311033a0
LeBowitz JH, Grubb JH, Maga JA, Schmiel DH, Vogler C, Sly WS (2004) Glycosylation-independent targeting enhances enzyme delivery to lysosomes and decreases storage in mucopolysaccharidosis type VII mice. Proc Natl Acad Sci USA 101:3083–3088. doi:10.1073/pnas.0308728100
Zhao K, Zhao G-M, Wu D, Soong Y, Birk AV, Schiller PW, Szeto HH (2004) Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem 279:34682–34690. doi:10.1074/jbc.M402999200
Schwarze SR, Ho A, Vocero-Akbani A, Dowdy SF (1999) In vivo protein transduction: delivery of a biologically active protein into the mouse. Science 285:1569–1572. doi:10.1126/science.285.5433.1569
Fischer R, Fotin-Mleczek M, Hufnagel H, Brock R (2005) Break on through to the other side—biophysics and cell biology shed light on cell-penetrating peptides. ChemBioChem 6:2126–2142. doi:10.1002/cbic.200500044
Morris MC, Deshayes S, Heitz F, Divita G (2008) Cell-penetrating peptides: from molecular mechanisms to therapeutics. Biol Cell 100:201–217. doi:10.1042/bc20070116
Zorko M, Langel Ü (2005) Cell-penetrating peptides: mechanism and kinetics of cargo delivery. Adv Drug Deliv Rev 57:529–545. doi:10.1016/j.addr.2004.10.010
Elzoghby AO, Samy WM, Elgindy NA (2012) Protein-based nanocarriers as promising drug and gene delivery systems. J Controlled Release 161:38–49. doi:10.1016/j.jconrel.2012.04.036
Numata K, Kaplan DL (2010) Silk-based delivery systems of bioactive molecules. Adv Drug Deliv Rev 62:1497–1508. doi:10.1016/j.addr.2010.03.009
Vivès E, Brodin P, Lebleu B (1997) A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J Biol Chem 272:16010–16017. doi:10.1074/jbc.272.25.16010
Pooga M, Hällbrink M, Zorko M, Langel Ü (1998) Cell penetration by transportan. FASEB J 12:67–77
Rothbard JB, Garlington S, Lin Q, Kirschberg T, Kreider E, McGrane PL, Wender PA, Khavari PA (2000) Conjugation of arginine oligomers to cyclosporin a facilitates topical delivery and inhibition of inflammation. Nat Med 6:1253–1257. doi:10.1038/81359
Green M, Loewenstein PM (1988) Autonomous functional domains of chemically synthesized human immunodeficiency virus Tat trans-activator protein. Cell 55:1179–1188. doi:10.1016/0092-8674(88)90262-0
Frankel AD, Pabo CO (1988) Cellular uptake of the Tat protein from human immunodeficiency virus. Cell 55:1189–1193. doi:10.1016/0092-8674(88)90263-2
Mishra A, Lai GH, Schmidt NW, Sun VZ, Rodriguez AR, Tong R, Tang L, Cheng J, Deming TJ, Kamei DT, Wong GCL (2011) Translocation of HIV TAT peptide and analogues induced by multiplexed membrane and cytoskeletal interactions. Proc Natl Acad Sci USA 108:16883–16888. doi:10.1073/pnas.1108795108
Akhtar S, Juliano RL (1992) Cellular uptake and intracellular fate of antisense oligonucleotides. Trends Cell Biol 2:139–144. doi:10.1016/0962-8924(92)90100-2
Bloomfield VA (1996) DNA condensation. Curr Opin Struct Biol 6:334–341. doi:10.1016/S0959-440X(96)80052-2
Adami RC, Collard WT, Gupta SA, Kwok KY, Bonadio J, Rice KG (1998) Stability of peptide-condensed plasmid DNA formulations. J Pharm Sci 87:678–683. doi:10.1021/js9800477
Abes S, Moulton HM, Clair P, Prevot P, Youngblood DS, Wu RP, Iversen PL, Lebleu B (2006) Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents. J Controlled Release 116:304–313. doi:10.1016/j.jconrel.2006.09.011
Abes S, Turner JJ, Ivanova GD, Owen D, Williams D, Arzumanov A, Clair P, Gait MJ, Lebleu B (2007) Efficient splicing correction by PNA conjugation to an R6-Penetratin delivery peptide. Nucleic Acids Res 35:4495–4502. doi:10.1093/nar/gkm418
Lundberg P, El-Andaloussi S, Sütlü T, Johansson H, Langel Ü (2007) Delivery of short interfering RNA using endosomolytic cell-penetrating peptides. FASEB J 21:2664–2671. doi:10.1096/fj.06-6502com
Vivès E, Schmidt J, Pèlegrin A (2008) Cell-penetrating and cell-targeting peptides in drug delivery. Biochim Biophys Acta Rev Cancer 1786:126–138. doi:10.1016/j.bbcan.2008.03.001
Crombez L, Divita G (2007) A non-covalent peptide-based strategy for siRNA delivery. Biochem Soc Trans 683:349–360. doi:10.1007/978-1-60761-919-2_25
Detzer A, Overhoff M, Wünsche W, Rompf M, Turner JJ, Ivanova GD, Gait MJ, Sczakiel G (2009) Increased RNAi is related to intracellular release of siRNA via a covalently attached signal peptide. RNA 15:627–636. doi:10.1261/rna.1305209
McManus MT, Sharp PA (2002) Gene silencing in mammals by small interfering RNAs. Nat Rev Genet 3:737–747. doi:10.1038/nrg908
Meade BR, Dowdy SF (2007) Exogenous siRNA delivery using peptide transduction domains/cell penetrating peptides. Adv Drug Deliv Rev 59:134–140. doi:10.1016/j.addr.2007.03.004
Meade BR, Dowdy SF (2008) Enhancing the cellular uptake of siRNA duplexes following noncovalent packaging with protein transduction domain peptides. Adv Drug Deliv Rev 60:530–536. doi:10.1016/j.addr.2007.10.004
Andaloussi S, Lehto T, Mäger I, Rosenthal-Aizman K, Oprea I, Simonson O, Sork H, Ezzat K, Copolovici D, Kurrikoff K, Viola J, Zaghloul E, Sillard R, Johansson H, Said Hassane F, Guterstam P, Suhorutšenko J, Moreno P, Oskolkov N, Hälldin J, Tedebark U, Metspalu A, Lebleu B, Lehtiö J, Smith C, Langel U (2011) Design of a peptide-based vector, PepFect6, for efficient delivery of siRNA in cell culture and systemically in vivo. Nucleic Acids Res 39:3972–3987. doi:10.1093/nar/gkq1299
Sioud M, Mobergslien A (2012) Efficient siRNA targeted delivery into cancer cells by gastrin-releasing peptides. Bioconjug Chem 23:1040–1049. doi:10.1021/bc300050j
Fang B, Guo HY, Zhang M, Jiang L, Ren FZ (2013) The six amino acid antimicrobial peptide bLFcin6 penetrates cells and delivers siRNA. FEBS J 280:1007–1017. doi:10.1111/febs.12093
Crombez L, Aldrian-Herrada G, Konate K, Nguyen QN, McMaster GK, Brasseur R, Heitz F, Divita G (2008) A new potent secondary amphipathic cell-penetrating peptide for siRNA delivery into mammalian cells. Mol Ther 17:95–103. doi:10.1038/mt.2008.215
Chiu Y-L, Ali A, Chu C-Y, Cao H, Rana TM (2004) Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cells. Chem Biol 11:1165–1175. doi:10.1016/j.chembiol.2004.06.006
Derossi D, Joliot AH, Chassaing G, Prochiantz A (1994) The third helix of the Antennapedia homeodomain translocates through biological membranes. J Biol Chem 269:10444–10450
Muratovska A, Eccles MR (2004) Conjugate for efficient delivery of short interfering RNA (siRNA) into mammalian cells. FEBS Lett 558:63–68. doi:10.1016/S0014-5793(03)01505-9
Veldhoen S, Laufer SD, Trampe A, Restle T (2006) Cellular delivery of small interfering RNA by a non-covalently attached cell-penetrating peptide: quantitative analysis of uptake and biological effect. Nucleic Acids Res 34:6561–6573. doi:10.1093/nar/gkl941
Kumar P, Wu H, McBride JL, Jung K-E, Hee Kim M, Davidson BL, Kyung Lee S, Shankar P, Manjunath N (2007) Transvascular delivery of small interfering RNA to the central nervous system. Nature 448:39–43. doi:10.1038/nature05901
Nakamura Y, Kogure K, Futaki S, Harashima H (2007) Octaarginine-modified multifunctional envelope-type nano device for siRNA. J Controlled Release 119:360–367. doi:10.1016/j.jconrel.2007.03.010
Johnson LN, Cashman SM, Kumar-Singh R (2007) Cell-penetrating peptide for enhanced delivery of nucleic acids and drugs to ocular tissues including retina and cornea. Mol Ther 16:107–114. doi:10.1038/sj.mt.6300324
Liu Z, Li M, Cui D, Fei J (2005) Macro-branched cell-penetrating peptide design for gene delivery. J Controlled Release 102:699–710. doi:10.1016/j.jconrel.2004.10.013
Liu BR, Lin M-D, Chiang H-J, Lee H-J (2012) Arginine-rich cell-penetrating peptides deliver gene into living human cells. Gene 505:37–45. doi:10.1016/j.gene.2012.05.053
Kichler A, Mason AJ, Bechinger B (2006) Cationic amphipathic histidine-rich peptides for gene delivery. Biochim Biophys Acta Biomembr 1758:301–307. doi:10.1016/j.bbamem.2006.02.005
Li W, Nicol F, Szoka FC Jr (2004) GALA: a designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery. Adv Drug Deliv Rev 56:967–985. doi:10.1016/j.addr.2003.10.041
Wyman TB, Nicol F, Zelphati O, Scaria PV, Plank C, Szoka FC (1997) Design, synthesis, and characterization of a cationic peptide that binds to nucleic acids and permeabilizes bilayers. Biochemistry 36:3008–3017. doi:10.1021/bi9618474
Gottschalk S, Sparrow JT, Hauer J, Mims MP, Leland FE, Woo SL, Smith LC (1996) A novel DNA-peptide complex for efficient gene transfer and expression in mammalian cells. Gene Ther 3:448–457
Rittner K, Benavente A, Bompard-Sorlet A, Heitz F, Divita G, Brasseur R, Jacobs E (2002) New basic membrane-destabilizing peptides for plasmid-based gene delivery in vitro and in vivo. Mol Ther 5:104–114. doi:10.1006/mthe.2002.0523
Rudolph C, Plank C, Lausier J, Schillinger U, Müller RH, Rosenecker J (2003) Oligomers of the arginine-rich motif of the HIV-1 TAT protein are capable of transferring plasmid DNA into cells. J Biol Chem 278:11411–11418. doi:10.1074/jbc.M211891200
Lakshmanan M, Kodama Y, Yoshizumi T, Sudesh K, Numata K (2012) Rapid and efficient gene delivery into plant cells using designed peptide carriers. Biomacromolecules 14:10–16. doi:10.1021/bm301275g
Kawamura KS, Sung M, Bolewska-Pedyczak E, Gariépy J (2006) Probing the impact of valency on the routing of arginine-rich peptides into eukaryotic cells. Biochemistry 45:1116–1127. doi:10.1021/bi051338e
Turner JJ, Ivanova GD, Verbeure B, Williams D, Arzumanov AA, Abes S, Lebleu B, Gait MJ (2005) Cell-penetrating peptide conjugates of peptide nucleic acids (PNA) as inhibitors of HIV-1 Tat-dependent trans-activation in cells. Nucleic Acids Res 33:6837–6849. doi:10.1093/nar/gki991
Resina S, Abes S, Turner JJ, Prevot P, Travo A, Clair P, Gait MJ, Thierry AR, Lebleu B (2007) Lipoplex and peptide-based strategies for the delivery of steric-block oligonucleotides. Int J Pharm 344:96–102. doi:10.1016/j.ijpharm.2007.04.039
Fisher L, Soomets U, Cortés Toro V, Chilton L, Jiang Y, Langel U, Iverfeldt K (2004) Cellular delivery of a double-stranded oligonucleotide NFkappaB decoy by hybridization to complementary PNA linked to a cell-penetrating peptide. Gene Ther 11:1264–1272. doi:10.1038/sj.gt.3302291
El-Andaloussi S, Johansson H, Magnusdottir A, Järver P, Lundberg P, Langel U (2005) TP10, a delivery vector for decoy oligonucleotides targeting the Myc protein. J Controlled Release 110:189–201. doi:10.1016/j.jconrel.2005.09.012
Nakamura Y, Yamada Y, Kogure K, Harashima H, Futaki S (2006) Significant and prolonged antisense effect of a multifunctional envelope-type nano device encapsulating antisense oligodeoxynucleotide. J Pharm Pharmacol 58:431–437. doi:10.1211/jpp.58.4.0002
Fletcher S, Honeyman K, Fall AM, Harding PL, Johnsen RD, Steinhaus JP, Moulton HM, Iversen PL, Wilton SD (2007) Morpholino oligomer-mediated exon skipping averts the onset of dystrophic pathology in the mdx mouse. Mol Ther 15:1587–1592. doi:10.1038/sj.mt.6300245
Gebski BL, Mann CJ, Fletcher S, Wilton SD (2003) Morpholino antisense oligonucleotide induced dystrophin exon 23 skipping in mdx mouse muscle. Hum Mol Genet 12:1801–1811. doi:10.1093/hmg/ddg196
Bais MV, Kumar S, Tiwari AK, Kataria RS, Nagaleekar VK, Shrivastava S, Chindera K (2008) Novel Rath peptide for intracellular delivery of protein and nucleic acids. Biochem Biophys Res Commun 370:27–32. doi:10.1016/j.bbrc.2008.03.023
Goun EA, Pillow TH, Jones LR, Rothbard JB, Wender PA (2006) Molecular transporters: synthesis of oligoguanidinium transporters and their application to drug delivery and real-time imaging. ChemBioChem 7:1497–1515. doi:10.1002/cbic.200600171
Kirschberg TA, VanDeusen CL, Rothbard JB, Yang M, Wender PA (2003) Arginine-based molecular transporters: the synthesis and chemical evaluation of releasable taxol-transporter conjugates. Org Lett 5:3459–3462. doi:10.1021/ol035234c
Dixon MJ, Bourré L, MacRobert AJ, Eggleston IM (2007) Novel prodrug approach to photodynamic therapy: Fmoc solid-phase synthesis of a cell permeable peptide incorporating 5-aminolaevulinic acid. Bioorg Med Chem Lett 17:4518–4522. doi:10.1016/j.bmcl.2007.05.095
Mazel M, Clair P, Rousselle C, Vidal P, Scherrmann J-M, Mathieu D, Temsamani J (2001) Doxorubicin-peptide conjugates overcome multidrug resistance. Anticancer Drugs 12:107–116. doi:10.1097/00001813-200102000-00003
Liang JF, Yang VC (2005) Synthesis of doxorubicin-peptide conjugate with multidrug resistant tumor cell killing activity. Bioorg Med Chem Lett 15:5071–5075. doi:10.1016/j.bmcl.2005.07.087
Eriste E, Kurrikoff K, Suhorutšenko J, Oskolkov N, Copolovici DM, Jones S, Laakkonen P, Howl J, Langel U (2013) Peptide-based glioma-targeted drug delivery vector gHoPe2. Bioconjugate Chem 24:305–313. doi:10.1021/bc300370w
Elmquist A, Lindgren M, Bartfai T, Langel U (2001) VE-cadherin-derived cell-penetrating peptide, pVEC, with carrier functions. Exp Cell Res 269:237–244. doi:10.1006/excr.2001.5316
Lindgren M, Rosenthal-Aizman K, Saar K, Eiríksdóttir E, Jiang Y, Sassian M, Östlund P, Hällbrink M, Langel U (2006) Overcoming methotrexate resistance in breast cancer tumour cells by the use of a new cell-penetrating peptide. Biochem Pharmacol 71:416–425. doi:10.1016/j.bcp.2005.10.048
Tan M, Lan K-H, Yao J, Lu C-H, Sun M, Neal CL, Lu J, Yu D (2006) Selective inhibition of ErbB2-overexpressing breast cancer in vivo by a novel TAT-based ErbB2-targeting signal transducers and activators of transcription 3-blocking peptide. Cancer Res 66:3764–3772. doi:10.1158/0008-5472.can-05-2747
Myrberg H, Zhang L, Mäe M, Langel U (2007) Design of a tumor-homing cell-penetrating peptide. Bioconjugate Chem 19:70–75. doi:10.1021/bc0701139
Anderson DC, Nichols E, Manger R, Woodle D, Barry M, Fritzberg AR (1993) Tumor cell retention of antibody Fab fragments is enhanced by an attached HIV TAT protein-derived peptide. Biochem Biophys Res Commun 194:876–884. doi:10.1006/bbrc.1993.1903
Cornelissen B, Hu M, McLarty K, Costantini D, Reilly RM (2007) Cellular penetration and nuclear importation properties of 111In-labeled and 123I-labeled HIV-1 tat peptide immunoconjugates in BT-474 human breast cancer cells. Nucl Med Biol 34:37–46. doi:10.1016/j.nucmedbio.2006.10.008
Hu M, Wang J, Chen P, Reilly RM (2006) 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 17:1280–1287. doi:10.1021/bc060053r
Škrlj N, Drevenšek G, Hudoklin S, Romih R, Čurin Šerbec V, Dolinar M (2013) Recombinant single-chain antibody with the Trojan peptide penetratin positioned in the linker region enables cargo transfer across the blood-brain barrier. Appl Biochem Biotechnol 169:159–169. doi:10.1007/s12010-012-9962-7
Xun Y, Pan Q, Tang Z, Chen X, Yu Y, Xi M, Zang G (2013) Intracellular-delivery of a single-chain antibody against hepatitis B core protein via cell-penetrating peptide inhibits hepatitis B virus replication in vitro. Int J Mol Med 31:369–376. doi:10.3892/ijmm.2012.1210
Morishita M, Kamei N, Ehara J, Isowa K, Takayama K (2007) A novel approach using functional peptides for efficient intestinal absorption of insulin. J Controlled Release 118:177–184. doi:10.1016/j.jconrel.2006.12.022
Wang H, Chen X, Chen Y, Sun L, Li G, Zhai M, Zhai W, Kang Q, Gao Y, Qi Y (2013) Antitumor activity of novel chimeric peptides derived from cyclinD/CDK4 and the protein transduction domain 4. Amino Acids 44:499–510. doi:10.1007/s00726-012-1360-5
McCusker CT, Wang Y, Shan J, Kinyanjui MW, Villeneuve A, Michael H, Fixman ED (2007) Inhibition of experimental allergic airways disease by local application of a cell-penetrating dominant-negative STAT-6 peptide. J Immunol 179:2556–2564
Hotchkiss RS, McConnell KW, Bullok K, Davis CG, Chang KC, Schwulst SJ, Dunne JC, Dietz GPH, Bähr M, McDunn JE, Karl IE, Wagner TH, Cobb JP, Coopersmith CM, Piwnica-Worms D (2006) TAT-BH4 and TAT-Bcl-xL peptides protect against sepsis-induced lymphocyte apoptosis in vivo. J Immunol 176:5471–5477
Orzáeza M, Mondragóna L, Marzo I, Sanclimens G, Messeguer À, Pérez-Payáa E, Vicent MJ (2007) Conjugation of a novel Apaf-1 inhibitor to peptide-based cell-membrane transporters: effective methods to improve inhibition of mitochondria-mediated apoptosis. Peptides 28:958–968. doi:10.1016/j.peptides.2007.02.014
Bleifuss E, Kammertoens T, Hutloff A, Quarcoo D, Dorner M, Straub P, Uckert W, Hildt E (2006) The translocation motif of hepatitis B virus improves protein vaccination. Cell Mol Life Sci 63:627–635. doi:10.1007/s00018-005-5548-7
Gros E, Deshayes S, Morris MC, Aldrian-Herrada G, Depollier J, Heitz F, Divita G (2006) A non-covalent peptide-based strategy for protein and peptide nucleic acid transduction. Biochim Biophys Acta Biomembr 1758:384–393. doi:10.1016/j.bbamem.2006.02.006
Heijne G (1990) The signal peptide. J Membr Biol 115:195–201. doi:10.1007/bf01868635
Cartier R, Reszka R (2002) Utilization of synthetic peptides containing nuclear localization signals for nonviral gene transfer systems. Gene Ther 9:157–167. doi:10.1038/sj.gt.3301635
Nigg EA (1997) Nucleocytoplasmic transport: signals, mechanisms and regulation. Nature 386:779–787. doi:10.1038/386779a0
Goldfarb DS, Gariepy J, Schoolnik G, Kornberg RD (1986) Synthetic peptides as nuclear localization signals. Nature 322:641–644. doi:10.1038/322641a0
Escriou V, Carrière M, Scherman D, Wils P (2003) NLS bioconjugates for targeting therapeutic genes to the nucleus. Adv Drug Deliv Rev 55:295–306. doi:10.1016/S0169-409X(02)00184-9
Collas P, Husebye H, Aleström P (1996) The nuclear localization sequence of the SV40 T antigen promotes transgene uptake and expression in zebrafish embryo nuclei. Transgenic Res 5:451–458. doi:10.1007/bf01980210
Subramanian A, Ranganathan P, Diamond SL (1999) Nuclear targeting peptide scaffolds for lipofection of nondividing mammalian cells. Nat Biotech 17:873–877. doi:10.1038/12860
Pan L, He Q, Liu J, Chen Y, Ma M, Zhang L, Shi J (2012) Nuclear-targeted drug delivery of TAT peptide-conjugated monodisperse mesoporous silica nanoparticles. J Am Chem Soc 134:5722–5725. doi:10.1021/ja211035w
Yu J, Xie X, Zheng M, Yu L, Zhang L, Zhao J, Jiang D, Che X (2012) Fabrication and characterization of nuclear localization signal-conjugated glycol chitosan micelles for improving the nuclear delivery of doxorubicin. Int J Nanomed 7:5079–5090. doi:10.2147/ijn.s36150
de Moura MB, dos Santos LS, Van Houten B (2010) Mitochondrial dysfunction in neurodegenerative diseases and cancer. Environ Mol Mutagen 51:391–405. doi:10.1002/em.20575
Schapira AH, Mann VM, Cooper JM, Krige D, Jenner PJ, Marsden CD (1992) Mitochondrial function in Parkinson’s disease. The royal kings and queens Parkinson’s disease research group. Ann Neurol 32(Suppl):S116–S124. doi:10.1002/ana.410320720
Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PLR, Jones PK, Petersen RB, Perry G, Smith MA (2001) Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci 21:3017–3023
Green K, Brand MD, Murphy MP (2004) Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes 53:S110–S118. doi:10.2337/diabetes.53.2007.S110
Di Lisa F, Kaludercic N, Carpi A, Menabo R, Giorgio M (2009) Mitochondria and vascular pathology. Pharmacol Rep 61:123–130
Horton KL, Stewart KM, Fonseca SB, Guo Q, Kelley SO (2008) Mitochondria-penetrating peptides. Chem Biol 15:375–382. doi:10.1016/j.chembiol.2008.03.015
Gaizo VD, MacKenzie JA, Payne RM (2003) Targeting proteins to mitochondria using TAT. Mol Genet Metab 80:170–180. doi:10.1016/j.ymgme.2003.08.017
Bolender N, Sickmann A, Wagner R, Meisinger C, Pfanner N (2008) Multiple pathways for sorting mitochondrial precursor proteins. EMBO Rep 9:42–49. doi:10.1038/sj.embor.7401126
Fonseca SB, Pereira MP, Mourtada R, Gronda M, Horton KL, Hurren R, Minden MD, Schimmer AD, Kelley SO (2011) Rerouting chlorambucil to mitochondria combats drug deactivation and resistance in cancer cells. Chem Biol 18:445–453. doi:10.1016/j.chembiol.2011.02.010
Luque-Ortega J, van’t Hof W, Veerman E, Saugar J, Rivas L (2008) Human antimicrobial peptide histatin 5 is a cell-penetrating peptide targeting mitochondrial ATP synthesis in Leishmania. FASEB J 22:1817–1828. doi:10.1096/fj.07-096081
Yu H, Koilkonda RD, Chou T-H, Porciatti V, Ozdemir SS, Chiodo V, Boye SL, Boye SE, Hauswirth WW, Lewin AS, Guy J (2012) Gene delivery to mitochondria by targeting modified adenoassociated virus suppresses Leber-hereditary optic neuropathy in a mouse model. Proc Natl Acad Sci USA 109:E1238–E1247. doi:10.1073/pnas.1119577109
Yu H, Ozdemir SS, Koilkonda RD, Chou TH, Porciatti V, Chiodo V, Boye SL, Hauswirth WW, Lewin AS, Guy J (2012) Mutant NADH dehydrogenase subunit 4 gene delivery to mitochondria by targeting sequence-modified adeno-associated virus induces visual loss and optic atrophy in mice. Mol vision 18:1668–1683
Yang H, Cai H, Wan L, Liu S, Li S, Cheng J, Lu X (2013) Bombesin analogue-mediated delivery preferentially enhances the cytotoxicity of a mitochondria-disrupting peptide in tumor cells. PLoS One 8:e57358. doi:10.1371/journal.pone.0057358
Shin JY, Chung YS, Kang B, Jiang HL, Yu DY, Han K, Chae C, Moon JH, Jang G, Cho MH (2013) Co-delivery of LETM1 and CTMP synergistically inhibits tumor growth in H-ras12 V liver cancer model mice. Cancer Gene Ther 20:186–194. doi:10.1038/cgt.2013.6
Grabowsky G, Desnick R (1981) Enzyme replacement in genetic diseases. In: Holcenberg J, Roberts J (eds) Enzymes as drugs. Wiley, New York
Maga JA, Zhou J, Kambampati R, Peng S, Wang X, Bohnsack RN, Thomm A, Golata S, Tom P, Dahms NM, Byrne BJ, LeBowitz JH (2013) Glycosylation-independent lysosomal targeting of acid α-glucosidase enhances muscle glycogen clearance in Pompe mice. J Biol Chem 288:1428–1438. doi:10.1074/jbc.M112.438663
Dekiwadia CD, Lawrie AC, Fecondo JV (2012) Peptide-mediated cell penetration and targeted delivery of gold nanoparticles into lysosomes. J Pept Sci 18:527–534. doi:10.1002/psc.2430
Loh Y, Shi H, Hu M, Yao SQ (2010) “Click” synthesis of small molecule-peptide conjugates for organelle-specific delivery and inhibition of lysosomal cysteine proteases. Chem Commun 46:8407–8409. doi:10.1039/c0cc03738a
Altman GH, Diaz F, Jakuba C, Calabro T, Horan RL, Chen J, Lu H, Richmond J, Kaplan DL (2003) Silk-based biomaterials. Biomaterials 24:401–416. doi:S0142961202003538
Wang Y, Kim HJ, Vunjak-Novakovic G, Kaplan DL (2006) Stem cell-based tissue engineering with silk biomaterials. Biomaterials 27:6064–6082. doi:10.1016/j.biomaterials.2006.07.008
Numata K, Kaplan DL (2011) Differences in cytotoxicity of beta-sheet peptides originated from silk and amyloid beta. Macromol Biosci 11:60–64. doi:10.1002/mabi.201000250
Numata K, Cebe P, Kaplan DL (2010) Mechanism of enzymatic degradation of beta-sheet crystals. Biomaterials 31:2926–2933. doi:10.1016/J.Biomaterials.2009.12.026
Kundu J, Chung YI, Kim YH, Tae G, Kundu SC (2010) Silk fibroin nanoparticles for cellular uptake and control release. Int J Pharm 388:242–250. doi:10.1016/j.ijpharm.2009.12.052
Rajkhowa R, Gil ES, Kluge J, Numata K, Wang LJ, Wang XD, Kaplan DL (2010) Reinforcing silk scaffolds with silk particles. Macromol Biosci 10:599–611. doi:10.1002/Mabi.200900358
Anumolu R, Gustafson JA, Magda JJ, Cappello J, Ghandehari H, Pease LF (2011) Fabrication of highly uniform nanoparticles from recombinant silk-elastin-like protein polymers for therapeutic agent delivery. ACS Nano 5:5374–5382. doi:10.1021/Nn103585f
Mandal BB, Kundu SC (2009) Self-assembled silk sericin/poloxamer nanoparticles as nanocarriers of hydrophobic and hydrophilic drugs for targeted delivery. Nanotechnology 20:355101. doi:10.1088/0957-4484/20/35/355101
Zhang YQ, Shen WD, Xiang RL, Zhuge LJ, Gao WJ, Wang WB (2007) Formation of silk fibroin nanoparticles in water-miscible organic solvent and their characterization. J Nanopart Res 9:885–900. doi:10.1007/S11051-006-9162-X
Zhang YQ, Wang YJ, Wang HY, Zhu L, Zhou ZZ (2011) Highly efficient processing of silk fibroin nanoparticle-L-asparaginase bioconjugates and their characterization as a drug delivery system. Soft Matter 7:9728–9736. doi:10.1039/C0sm01332c
Zhu L, Hu RP, Wang HY, Wang YJ, Zhang YQ (2011) Bioconjugation of neutral protease on silk fibroin nanoparticles and application in the controllable hydrolysis of sericin. J Agric Food Chem 59:10298–10302. doi:10.1021/Jf202036v
Gupta V, Aseh A, Rios CN, Aggarwal BB, Mathur AB (2009) Fabrication and characterization of silk fibroin-derived curcumin nanoparticles for cancer therapy. Int J Nanomedicine 4:115–122. doi:10.2147/IJN.S5581
Yan HB, Zhang YQ, Ma YL, Zhou LX (2009) Biosynthesis of insulin-silk fibroin nanoparticles conjugates and in vitro evaluation of a drug delivery system. J Nanopart Res 11:1937–1946. doi:10.1007/S11051-008-9549-Y
Hermanson KD, Huemmerich D, Scheibel T, Bausch AR (2007) Engineered microcapsules fabricated from reconstituted spider silk. Adv Mater 19:1810–1815. doi:10.1002/Adma.200602709
Lammel A, Schwab M, Slotta U, Winter G, Scheibel T (2008) Processing conditions for the formation of spider silk microspheres. Chemsuschem 1:413–416. doi:10.1002/Cssc.200800030
Numata K, Yamazaki S, Naga N (2012) Biocompatible and biodegradable dual-drug release system based on silk hydrogel containing silk nanoparticles. Biomacromolecules 13:1383–1389. doi:10.1021/bm300089a
Numata K, Hamasaki J, Subramanian B, Kaplan DL (2010) Gene delivery mediated by recombinant silk proteins containing cationic and cell binding motifs. J Controlled Release 146:136–143. doi:10.1016/J.Jconrel.2010.05.006
Numata K, Kaplan DL (2010) Silk-based gene carriers with cell membrane destabilizing peptides. Biomacromolecules 11:3189–3195. doi:10.1021/Bm101055m
Numata K, Mieszawska-Czajkowska AJ, Kvenvold LA, Kaplan DL (2012) Silk-based nanocomplexes with tumor-homing peptides for tumor-specific gene delivery. Macromol Biosci 12:75–82. doi:10.1002/mabi.201100274
Numata K, Reagan MR, Goldstein RH, Rosenblatt M, Kaplan DL (2011) Spider silk-based gene carriers for tumor cell-specific delivery. Bioconjug Chem 22:1605–1610. doi:10.1021/bc200170u
Numata K, Subramanian B, Currie HA, Kaplan DL (2009) Bioengineered silk protein-based gene delivery systems. Biomaterials 30:5775–5784. doi:10.1016/j.biomaterials.2009.06.028
Oba M, Fukushima S, Kanayama N, Aoyagi K, Nishiyama N, Koyama H, Kataoka K (2007) Cyclic RGD peptide-conjugated polyplex micelles as a targetable gene delivery system directed to cells possessing alphavbeta3 and alphavbeta5 integrins. Bioconjug Chem 18:1415–1423. doi:10.1021/Bc0700133
Kim WJ, Yockman JW, Lee M, Jeong JH, Kim YH, Kim SW (2005) Soluble Flt-1 gene delivery using PEI-g-PEG-RGD conjugate for anti-angiogenesis. J Controlled Release 106:224–234. doi:10.1016/J.Jconrel.2005.04.016
Connelly JT, Garcia AJ, Levenston ME (2007) Inhibition of in vitro chondrogenesis in RGD-modified three-dimensional alginate gels. Biomaterials 28:1071–1083. doi:10.1016/J.Biomaterials.2006.10.006
Renigunta A, Krasteva G, Konig P, Rose F, Klepetko W, Grimminger F, Seeger W, Hanze J (2006) DNA transfer into human lung cells is improved with Tat-RGD peptide by Caveoli-mediated endocytosis. Bioconjug Chem 17:327–334. doi:10.1021/Bc050263o
Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279:377–380. doi:10.1126/Science.279.5349.377
Christian S, Pilch J, Akerman ME, Porkka K, Laakkonen P, Ruoslahti E (2003) Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels. J Cell Biol 163:871–878. doi:10.1083/Jcb.200304132
Porkka K, Laakkonen P, Hoffman JA, Bernasconi M, Ruoslahti E (2002) A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo. Proc Natl Acad Sci USA 99:7444–7449. doi:10.1073/Pnas.062189599
Hoffman JA, Giraudo E, Singh M, Zhang LL, Inoue M, Porkka K, Hanahan D, Ruoslahti E (2003) Progressive vascular changes in a transgenic mouse model of squamous cell carcinoma. Cancer Cell 4:383–391. doi:10.1016/S1535-6108(03)00273-3
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag London
About this chapter
Cite this chapter
Chuah, JA., Kaplan, D.L., Numata, K. (2014). Engineering Peptide-based Carriers for Drug and Gene Delivery. In: Cai, W. (eds) Engineering in Translational Medicine. Springer, London. https://doi.org/10.1007/978-1-4471-4372-7_25
Download citation
DOI: https://doi.org/10.1007/978-1-4471-4372-7_25
Published:
Publisher Name: Springer, London
Print ISBN: 978-1-4471-4371-0
Online ISBN: 978-1-4471-4372-7
eBook Packages: EngineeringEngineering (R0)