Cationic and amphipathic cell-penetrating peptides (CPPs): Their structures and in vivo studies in drug delivery

Frontiers of Chemical Science and Engineering

Volumn 9, Issue 4, 2015, Pages 407-427

  Zaro, Jennica L ^a   Shen, Wei Chiang ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

amphipathic peptides; cell penetrating peptides; drug delivery

Indexed keywords

EID: 84948569372     PISSN: 20950179     EISSN: 20950187     Source Type: Journal    
DOI: 10.1007/s11705-015-1538-y     Document Type: Review

References (208)

1. Green M, Loewenstein P M. Autonomous functional domains of chemically synthesized human immunodeficiency virus tat transactivator protein. Cell, 1988, 55(6): 1179–1188
2. Frankel A D, Pabo C O. Cellular uptake of the tat protein from human immunodeficiency virus. Cell, 1988, 55(6): 1189–1193
3. Patel L N, Zaro J L, Shen W C. Cell penetrating peptides: Intracellular pathways and pharmaceutical perspectives. Pharmaceutical Research, 2007, 24(11): 1977–1992
4. Vasconcelos L, Madani F, Arukuusk P, Parnaste L, Graslund A, Langel U. Effects of cargo molecules on membrane perturbation caused by transportan10 based cell-penetrating peptides. Biochimica et Biophysica Acta, 2014, 1838(12): 3118–3129
5. Grdisa M. The delivery of biologically active (therapeutic) peptides and proteins into cells. Current Medicinal Chemistry, 2011, 18(9): 1373–1379
6. Dietz G P, Bahr M. Delivery of bioactive molecules into the cell: The Trojan horse approach. Molecular and Cellular Neurosciences, 2004, 27(2): 85–131
7. Copolovici D M, Langel K, Eriste E, Langel U. Cell-penetrating peptides: Design, synthesis, and applications. ACS Nano, 2014, 8 (3): 1972–1994
8. Bechinger B, Aisenbrey C. The polymorphic nature of membraneactive peptides from biophysical and structural investigations. Current Protein & Peptide Science, 2012, 13(7): 602–610
9. El-Andaloussi S, Holm T, Langel U. Cell-penetrating peptides: Mechanisms and applications. Current Pharmaceutical Design, 2005, 11(28): 3597–3611
10. Walrant A, Bechara C, Alves I D, Sagan S. Molecular partners for interaction and cell internalization of cell-penetrating peptides: How identical are they? Nanomedicine (London), 2012, 7(1): 133–143
11. Lewis H D, Husain A, Donnelly R J, Barlos D, Riaz S, Ginjupalli K, Shodeinde A, Barton B E. Creation of a novel peptide with enhanced nuclear localization in prostate and pancreatic cancer cell lines. BMC Biotechnology, 2010, 10(1): 79
12. Ragin A D, Morgan R A, Chmielewski J. Cellular import mediated by nuclear localization signal peptide sequences. Chemistry & Biology, 2002, 9(8): 943–948
13. Sadler K, Eom K D, Yang J L, Dimitrova Y, Tam J P. Translocating proline-rich peptides from the antimicrobial peptide bactenecin 7. Biochemistry, 2002, 41(48): 14150–14157
14. Jha D, Mishra R, Gottschalk S, Wiesmuller K H, Ugurbil K, Maier M E, Engelmann J. CyLoP-1: A novel cysteine-rich cellpenetrating peptide for cytosolic delivery of cargoes. Bioconjugate Chemistry, 2011, 22(3): 319–328
15. De Coupade C, Fittipaldi A, Chagnas V, Michel M, Carlier S, Tasciotti E, Darmon A, Ravel D, Kearsey J, Giacca M, Cailler F. Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules. Biochemical Journal, 2005, 390(2): 407–418
16. Futaki S, Suzuki T, Ohashi W, Yagami T, Tanaka S, Ueda K, Sugiura Y. Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. Journal of Biological Chemistry, 2001, 276(8): 5836–5858
17. Nakase I, Hirose H, Tanaka G, Tadokoro A, Kobayashi S, Takeuchi T, Futaki S. Cell-surface accumulation of flock house virus-derived peptide leads to efficient internalization via macropinocytosis. Molecular Therapy, 2009, 17(11): 1868–1876
18. Langedijk J P, Olijhoek T, Schut D, Autar R, Meloen R H. New transport peptides broaden the horizon of applications for peptidic pharmaceuticals. Molecular Diversity, 2004, 8(2): 101–111
19. Bong D T, Steinem C, Janshoff A, Johnson J E, Reza Ghadiri M. A highly membrane-active peptide in Flock House virus: Implications for the mechanism of nodavirus infection. Chemistry & Biology, 1999, 6(7): 473–481
20. Bertrand J R, Malvy C, Auguste T, Toth G K, Kiss-Ivankovits O, Illyes E, Hollosi M, Bottka S, Laczko I. Synthesis and studies on cell-penetrating peptides. Bioconjugate Chemistry, 2009, 20(7): 1307–1314
21. Trehin R, Krauss U, Beck-Sickinger A G, Merkle H P, Nielsen H M. Cellular uptake but low permeation of human calcitoninderived cell penetrating peptides and Tat(47-57) through welldifferentiated epithelial models. Pharmaceutical Research, 2004, 21(7): 1248–1256
22. Cascales L, Henriques S T, Kerr M C, Huang Y H, Sweet M J, Daly N L, Craik D J. Identification and characterization of a new family of cell-penetrating peptides: Cyclic cell-penetrating peptides. Journal of Biological Chemistry, 2011, 286(42): 36932–36943
23. Thoren P E, Persson D, Isakson P, Goksor M, Onfelt A, Norden B. Uptake of analogs of penetratin, Tat(48-60) and oligoarginine in live cells. Biochemical and Biophysical Research Communications, 2003, 307(1): 100–107
24. Fischer P M, Zhelev N Z, Wang S, Melville J E, Fahraeus R, Lane D P. Structure-activity relationship of truncated and substituted analogues of the intracellular delivery vector Penetratin. Journal of Peptide Research, 2000, 55(2): 163–172
25. Derossi D, Calvet S, Trembleau A, Brunissen A, Chassaing G, Prochiantz A. Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent. Journal of Biological Chemistry, 1996, 271(30): 18188–18193
26. El-Andaloussi S, Johansson H J, Holm T, Langel U. A novel cellpenetrating peptide, M918, for efficient delivery of proteins and peptide nucleic acids. Molecular Therapy, 2007, 15(10): 1820–1826
27. Duchardt F, Ruttekolk I R, VerdurmenWP, Lortat-Jacob H, Burck J, Hufnagel H, Fischer R, van den Heuvel M, Lowik D W, Vuister G W, Ulrich A, de Waard M, Brock R. A cell-penetrating peptide derived from human lactoferrin with conformation-dependent uptake efficiency. Journal of Biological Chemistry, 2009, 284 (52): 36099–36108
28. Scheller A, Oehlke J, Wiesner B, Dathe M, Krause E, Beyermann M, Melzig M, Bienert M. Structural requirements for cellular uptake of alpha-helical amphipathic peptides. Journal of Peptide Science, 1999, 5(4): 185–194
29. Jones S W, Christison R, Bundell K, Voyce C J, Brockbank S M, Newham P, Lindsay M A. Characterisation of cell-penetrating peptide-mediated peptide delivery. British Journal of Pharmacology, 2005, 145(8): 1093–1102
30. Verdurmen W P, Bovee-Geurts P H, Wadhwani P, Ulrich A S, Hallbrink M, van Kuppevelt T H, Brock R. Preferential uptake of L-versus D-amino acid cell-penetrating peptides in a cell typedependent manner. Chemistry & Biology, 2011, 18(8): 1000–1010
31. Drin G, Cottin S, Blanc E, Rees A R, Temsamani J. Studies on the internalization mechanism of cationic cell-penetrating peptides. Journal of Biological Chemistry, 2003, 278(33): 31192–31201
32. Kilk K, Magzoub M, Pooga M, Eriksson L E, Langel U, Graslund A. Cellular internalization of a cargo complex with a novel peptide derived from the third helix of the islet-1 homeodomain. Comparison with the penetratin peptide. Bioconjugate Chemistry, 2001, 12(6): 911–916
33. Han K, JeonMJ, Kim K A, Park J, Choi S Y. Efficient intracellular delivery of GFP by homeodomains of Drosophila Fushi-tarazu and Engrailed proteins. Molecules and Cells, 2000, 10(6): 728–732
34. Elmquist A, Hansen M, Langel U. Structure-activity relationship study of the cell-penetrating peptide pVEC. Biochimica et Biophysica Acta, 2006, 1758(6): 721–729
35. Wender P A, Mitchell D J, Pattabiraman K, Pelkey E T, Steinman L, Rothbard J B. The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters. Proceedings of the National Academy of Sciences of the United States of America, 2000, 97(24): 13003–13008
36. 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. International Journal of Molecular Medicine, 2010, 25(1): 41–51
37. Takeshima K, Chikushi A, Lee K K, Yonehara S, Matsuzaki K. Translocation of analogues of the antimicrobial peptides magainin and buforin across human cell membranes. Journal of Biological Chemistry, 2003, 278(2): 1310–1315
38. Richard J P, Melikov K, Vives E, Ramos C, Verbeure B, Gait M J, Chernomordik L V, Lebleu B. Cell-penetrating peptides. A reevaluation of the mechanism of cellular uptake. Journal of Biological Chemistry, 2003, 278(1): 585–590
39. Vives E, Brodin P, Lebleu B. A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. Journal of Biological Chemistry, 1997, 272(25): 16010–16017
40. Hariton-Gazal E, Feder R, Mor A, Graessmann A, Brack-Werner R, Jans D, Gilon C, Loyter A. Targeting of nonkaryophilic cellpermeable peptides into the nuclei of intact cells by covalently attached nuclear localization signals. Biochemistry, 2002, 41(29): 9208–9214
41. Patel L N, Wang J, Kim K J, Borok Z, Crandall E D, Shen W C. Conjugation with cationic cell-penetrating peptide increases pulmonary absorption of insulin. Molecular Pharmaceutics, 2009, 6(2): 492–503
42. Zaro J L, Shen W C. Quantitative comparison of membrane transduction and endocytosis of oligopeptides. Biochemical and Biophysical Research Communications, 2003, 307(2): 241–247
43. Zaro J L, Shen W C. Evidence that membrane transduction of oligoarginine does not require vesicle formation. Experimental Cell Research, 2005, 307(1): 164–173
44. Park Y J, Chang L C, Liang J F, Moon C, Chung C P, Yang V C. Nontoxic membrane translocation peptide from protamine, low molecular weight protamine (LMWP), for enhanced intracellular protein delivery: in vitro and in vivo study. FASEB Journal, 2005, 19(11): 1555–1557
45. Wu F L, Yeh T H, Chen Y L, Chiu Y C, Cheng J C, Wei M F, Shen L J. Intracellular delivery of recombinant arginine deiminase (rADI) by heparin-binding hemagglutinin adhesion peptide restores sensitivity in rADI-resistant cancer cells. Molecular Pharmaceutics, 2014, 11(8): 2777–2786
46. Yang Z, Jiang Z, Cao Z, Zhang C, Gao D, Luo X, Zhang X, Luo H, Jiang Q, Liu J. Multifunctional non-viral gene vectors with enhanced stability, improved cellular and nuclear uptake capability, and increased transfection efficiency. Nanoscale, 2014, 6(17): 10193–10206
47. Morris M C, Depollier J, Mery J, Heitz F, Divita G. A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nature Biotechnology, 2001, 19(12): 1173–1176
48. Kurzawa L, Pellerano M, Morris M C. PEP and CADY-mediated delivery of fluorescent peptides and proteins into living cells. Biochimica et Biophysica Acta, 2010, 1798(12): 2274–2285
49. Lin Y Z, Yao S Y, Veach R A, Torgerson T R, Hawiger J. Inhibition of nuclear translocation of transcription factor NF-kappa B by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. Journal of Biological Chemistry, 1995, 270(24): 14255–14258
50. Soomets U, Lindgren M, Gallet X, Hallbrink M, Elmquist A, Balaspiri L, Zorko M, Pooga M, Brasseur R, Langel U. Deletion analogues of transportan. Biochimica et Biophysica Acta, 2000, 1467(1): 165–176
51. Kobayashi S, Nakase I, Kawabata N, Yu H H, Pujals S, Imanishi M, Giralt E, Futaki S. Cytosolic targeting of macromolecules using a pH-dependent fusogenic peptide in combination with cationic liposomes. Bioconjugate Chemistry, 2009, 20(5): 953–959
52. El-Sayed A, Futaki S, Harashima H. Delivery of macromolecules using arginine-rich cell-penetrating peptides: Ways to overcome endosomal entrapment. AAPS Journal, 2009, 11(1): 13–22
53. Wyman T B, Nicol F, Zelphati O, Scaria P V, Plank C, Szoka F C J. Design, synthesis, and characterization of a cationic peptide that binds to nucleic acids and permeabilizes bilayers. Biochemistry, 1997, 36(10): 3008–3017
54. Wada S, Tsuda H, Okada T, Urata H. Cellular uptake of aibcontaining amphipathic helix peptide. Bioorganic & Medicinal Chemistry Letters, 2011, 21(19): 5688–5691
55. Zaro J L, Vekich J E, Tran T, Shen W C. Nuclear localization of cell-penetrating peptides is dependent on endocytosis rather than cytosolic delivery in CHO cells. Molecular Pharmaceutics, 2009, 6 (2): 337–344
56. Gomez J A, Chen J, Ngo J, Hajkova D, Yeh I J, Gama V, Miyagi M, Matsuyama S. Cell-penetrating penta-peptides (CPP5s): Measurement of cell entry and protein-transduction activity. Pharmaceuticals (Basel, Switzerland), 2010, 3(12): 3594–3613
57. Fretz M M, Penning N A, Al-Taei S, Futaki S, Takeuchi T, Nakase I, Storm G, Jones A T. Temperature, concentration- and cholesterol-dependent translocation of L- and D-octa-arginine across the plasma and nuclear membrane of CD34 + leukaemia cells. Biochemical Journal, 2007, 403(2): 335–342
58. Zaro J L, Rajapaksa T E, Okamoto C T, Shen W C. Membrane transduction of oligoarginine in HeLa cells is not mediated by macropinocytosis. Molecular Pharmaceutics, 2006, 3(2): 181–186
59. Cohen-Avrahami M, Libster D, Aserin A, Garti N. Sodium diclofenac and cell-penetrating peptides embedded in H(II) mesophases: Physical characterization and delivery. Journal of Physical Chemistry B, 2011, 115(34): 10189–10197
60. Sheng J, Oyler G, Zhou B, Janda K, Shoemaker C B. Identification and characterization of a novel cell-penetrating peptide. Biochemical and Biophysical Research Communications, 2009, 382(2): 236–240
61. Shen WC, Ryser H J. Conjugation of poly-L-lysine to albumin and horseradish peroxidase: A novel method of enhancing the cellular uptake of proteins. Proceedings of the National Academy of Sciences of the United States of America, 1978, 75(4): 1872–1876
62. Ryser H J, Shen W C, Merk F B. Membrane transport of macromolecules: New carrier functions of proteins and poly(amino acids). Life Sciences, 1978, 22(13–15): 1253–1260
63. Pardridge W M, Buciak J L, Kang Y S, Boado R J. Protaminemediated transport of albumin into brain and other organs of the rat. Binding and endocytosis of protamine-albumin complex by microvascular endothelium. Journal of Clinical Investigation, 1993, 92(5): 2224–2229
64. Wu G Y, Wu C H. Evidence for targeted gene delivery to Hep G2 hepatoma cells in vitro. Biochemistry, 1988, 27(3): 887–892
65. Cotten M, Langle-Rouault F, Kirlappos H, Wagner E, Mechtler K, Zenke M, Beug H, Birnstiel M L. Transferrin-polycation-mediated introduction of DNA into human leukemic cells: Stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels. Proceedings of the National Academy of Sciences of the United States of America, 1990, 87(11): 4033–4037
66. Ryser H J, Shen W C. Conjugation of methotrexate to poly(Llysine) increases drug transport and overcomes drug resistance in cultured cells. Proceedings of the National Academy of Sciences of the United States of America, 1978, 75(8): 3867–3870
67. Shen W C, Ryser H J. Poly (L-lysine) and poly (D-lysine) conjugates of methotrexate: Different inhibitory effect on drug resistant cells. Molecular Pharmacology, 1979, 16(2): 614–622
68. Ryser H J, Shen W C. Conjugation of methotrexate to poly (Llysine) as a potential way to overcome drug resistance. Cancer, 1980, 45(5 Suppl): 1207–1211
69. Han K, Jeon M J, Kim S H, Ki D, Bahn J H, Lee K S, Park J, Choi S Y. Efficient intracellular delivery of an exogenous protein GFP with genetically fused basic oligopeptides. Molecules and Cells, 2001, 12(2): 267–271
70. Rothbard J B, Jessop T C, Lewis R S, Murray B A, Wender P A. Role of membrane potential and hydrogen bonding in the mechanism of translocation of guanidinium-rich peptides into cells. Journal of the American Chemical Society, 2004, 126(31): 9506–9507
71. Goncalves E, Kitas E, Seelig J. Binding of oligoarginine to membrane lipids and heparan sulfate: Structural and thermodynamic characterization of a cell-penetrating peptide. Biochemistry, 2005, 44(7): 2692–2702
72. Gelman R A, Glaser D N, Blackwell J. Interaction between chondroitin-6-sulfate and poly-L-arginine in aqueous solution. Biopolymers, 1973, 12(6): 1223–1232
73. Richard J P, Melikov K, Brooks H, Prevot P, Lebleu B, Chernomordik L V. Cellular uptake of unconjugated TAT peptide involves clathrin-dependent endocytosis and heparan sulfate receptors. Journal of Biological Chemistry, 2005, 280(15): 15300–15306
74. Jiao C Y, Delaroche D, Burlina F, Alves I D, Chassaing G, Sagan S. Translocation and endocytosis for cell-penetrating peptide internalization. Journal of Biological Chemistry, 2009, 284(49): 33957–33965
75. Zaro J L, Shen W C. Cytosolic delivery of a p16-peptide oligoarginine conjugate for inhibiting proliferation of MCF7 cells. Journal of Controlled Release, 2005, 108(2–3): 409–417
76. Fei L, Ren L, Zaro J L, Shen W C. The influence of net charge and charge distribution on cellular uptake and cytosolic localization of arginine-rich peptides. Journal of Drug Targeting, 2011, 19(8): 675–680
77. Law M, Jafari M, Chen P. Physicochemical characterization of siRNA-peptide complexes. Biotechnology Progress, 2008, 24(4): 957–963
78. Pace C N, Scholtz J M. A helix propensity scale based on experimental studies of peptides and proteins. Biophysical Journal, 1998, 75(1): 422–442, 7
79. Hong M, Su Y. Structure and dynamics of cationic membrane peptides and proteins: Insights from solid-state NMR. Protein Science, 2011, 20(4): 641–655
80. 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
81. Gelman R A, Blackwell J. Heparin-polypeptide interactions in aqueous solution. Archives of Biochemistry and Biophysics, 1973, 159(1): 427–433
82. Shen W C, Ryser H J. Poly(L-lysine) has different membrane transport and drug-carrier properties when complexed with heparin. Proceedings of the National Academy of Sciences of the United States of America, 1981, 78(12): 7589–7593
83. Su Y, Doherty T, Waring A J, Ruchala P, Hong M. Roles of arginine and lysine residues in the translocation of a cellpenetrating peptide from (13)C, (31)P, and (19)F solid-state NMR. Biochemistry, 2009, 48(21): 4587–4595
84. Clark K S, Svetlovics J, McKeown A N, Huskins L, Almeida P F. What determines the activity of antimicrobial and cytolytic peptides in model membranes. Biochemistry, 2011, 50(37): 7919–7932
85. Alves I D, Goasdoue N, Correia I, Aubry S, Galanth C, Sagan S, Lavielle S, Chassaing G. Membrane interaction and perturbation mechanisms induced by two cationic cell penetrating peptides with distinct charge distribution. Biochimica et Biophysica Acta, 2008, 1780(7-8): 948–959
86. Derossi D, Joliot A H, Chassaing G, Prochiantz A. The third helix of the Antennapedia homeodomain translocates through biological membranes. Journal of Biological Chemistry, 1994, 269(14): 10444–10450
87. Kaplan I M, Wadia J S, Dowdy S F. Cationic TAT peptide transduction domain enters cells by macropinocytosis. Journal of Controlled Release, 2005, 102(1): 247–253
88. Wadia J S, Stan R V, Dowdy S F. Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nature Medicine, 2004, 10(3): 310–315
89. Yesylevskyy S, Marrink S J, Mark A E. Alternative mechanisms for the interaction of the cell-penetrating peptides penetratin and the TAT peptide with lipid bilayers. Biophysical Journal, 2009, 97 (1): 40–49
90. Fittipaldi A, Ferrari A, Zoppe M, Arcangeli C, Pellegrini V, Beltram F, Giacca M. Cell membrane lipid rafts mediate caveolar endocytosis of HIV-1 Tat fusion proteins. Journal of Biological Chemistry, 2003, 278(36): 34141–34149
91. Ferrari M E, Nguyen C M, Zelphati O, Tsai Y, Felgner P L. Analytical methods for the characterization of cationic lipidnucleic acid complexes. Human Gene Therapy, 1998, 9(3): 341–351
92. Qian Z, LaRochelle J R, Jiang B, Lian W, Hard R L, Selner N G, Luechapanichkul R, Barrios A M, Pei D. Early endosomal escape of a cyclic cell-penetrating peptide allows effective cytosolic cargo delivery. Biochemistry, 2014, 53(24): 4034–4046
93. Lundberg P, El-Andaloussi S, Sutlu T, Johansson H, Langel U. Delivery of short interfering RNA using endosomolytic cellpenetrating peptides. FASEB Journal, 2007, 21(11): 2664–2671
94. Yang S T, Zaitseva E, Chernomordik L V, Melikov K. Cellpenetrating peptide induces leaky fusion of liposomes containing late endosome-specific anionic lipid. Biophysical Journal, 2010, 99 (8): 2525–2533
95. Deshayes S, Plenat T, Charnet P, Divita G, Molle G, Heitz F. Formation of transmembrane ionic channels of primary amphipathic cell-penetrating peptides. Consequences on the mechanism of cell penetration. Biochimica et Biophysica Acta, 2006, 1758 (11): 1846–1851
96. Kenien R, Shen W C, Zaro J L. Vesicle-to-cytosol transport of disulfide-linked cargo mediated by an amphipathic cell-penetrating peptide. Journal of Drug Targeting, 2012, 20(9): 793–800
97. Kenien R, Zaro J L, Shen W C. MAP-mediated nuclear delivery of a cargo protein. Journal of Drug Targeting, 2012, 20(4): 329–337
98. Shai Y. Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by a-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochimica et Biophysica Acta, 1999, 1462(1–2): 55–70
99. Matsuzaki K, Sugishita K, Miyajima K. Interactions of an antimicrobial peptide, magainin 2, with lipopolysaccharide-containing liposomes as a model for outer membranes of gramnegative bacteria. FEBS Letters, 1999, 449(2–3): 221–224
100. Yang L, Harroun T A, Weiss T M, Ding L, Huang H W. Barrelstave model or toroidal model? A case study on melittin pores. Biophysical Journal, 2001, 81(3): 1475–1485
101. Berlose J P, Convert O, Derossi D, Brunissen A, Chassaing G. Conformational and associative behaviours of the third helix of antennapedia homeodomain in membrane-mimetic environments. European Journal of Biochemistry, 1996, 242(2): 372–386
102. Mor A, Nguyen V H, Delfour A, Migliore-Samour D, Nicolas P. Isolation, amino acid sequence, and synthesis of dermaseptin, a novel antimicrobial peptide of amphibian skin. Biochemistry, 1991, 30(36): 8824–8830
103. Matsuzaki K, Murase O, Fujii N, Miyajima K. An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation. Biochemistry, 1996, 35(35): 11361–11368
104. Matsuzaki K, Murase O, Fujii N, Miyajima K. Translocation of a channel-forming antimicrobial peptide, magainin 2, across lipid bilayers by forming a pore. Biochemistry, 1995, 34(19): 6521–6526
105. Ludtke S J, He K, Heller W T, Harroun T A, Yang L, Huang H W. Membrane pores induced by magainin. Biochemistry, 1996, 35 (43): 13723–13728
106. Brauner J W, Mendelsohn R, Prendergast F G. Attenuated total reflectance Fourier transform infrared studies of the interaction of melittin, two fragments of melittin, and δ-hemolysin with phosphatidylcholines. Biochemistry, 1987, 26(25): 8151–8158
107. Frey S, Tamm L K. Orientation of melittin in phospholipid bilayers. A polarized attenuated total reflection infrared study. Biophysical Journal, 1991, 60(4): 922–930
108. Mueller J, Kretzschmar I, Volkmer R, Boisguerin P. Comparison of cellular uptake using 22 CPPs in 4 different cell lines. Bioconjugate Chemistry, 2008, 19(12): 2363–2374
109. Saar K, Lindgren M, Hansen M, Eiriksdottir E, Jiang Y, Rosenthal- Aizman K, Sassian M, Langel U. Cell-penetrating peptides: A comparative membrane toxicity study. Analytical Biochemistry, 2005, 345(1): 55–65
110. El-Andaloussi S, Jarver P, Johansson H J, Langel U. Cargodependent cytotoxicity and delivery efficacy of cell-penetrating peptides: A comparative study. Biochemical Journal, 2007, 407(2): 285–292
111. Rothbard J B, Jessop T C, Lewis R S, Murray B A, Wender P A. Role of membrane potential and hydrogen bonding in the mechanism of translocation of guanidinium-rich peptides into cells. Journal of the American Chemical Society, 2004, 126(31): 9506–9507
112. Zaro J L, Shen W C. Quantitative comparison of membrane transduction and endocytosis of oligopeptides. Biochemical and Biophysical Research Communications, 2003, 307(2): 241–247
113. Zaro J L, Shen W C. Evidence that membrane transduction of oligoarginine does not require vesicle formation. Experimental Cell Research, 2005, 307(1): 164–173
114. Patel L N, Zaro J L, Shen W C. Cell penetrating peptides: Intracellular pathways and pharmaceutical perspectives. Pharmaceutical Research, 2007, 24(11): 1977–1992
115. Sawant R, Torchilin V. Intracellular transduction using cellpenetrating peptides. Molecular BioSystems, 2010, 6(4): 628–640
116. Schmidt N, Mishra A, Lai G H, Wong G C L. Arginine-rich cellpenetrating peptides. FEBS Letters, 2010, 584(9): 1806–1813
117. Wender P A, Galliher W C, Goun E A, Jones L R, Pillow T H. The design of guanidinium-rich transporters and their internalization mechanisms. Advanced Drug Delivery Reviews, 2008, 60(4–5): 452–472
118. Ziegler A. Thermodynamic studies and binding mechanisms of cell-penetrating peptides with lipids and glycosaminoglycans. Advanced Drug Delivery Reviews, 2008, 60(4–5): 580–597
119. Jiao C Y, Delaroche D, Burlina F, Alves I D, Chassaing G, Sagan S. Translocation and endocytosis for cell-penetrating peptideinternalization. Journal of Biological Chemistry, 2009, 284(49): 33957–33965
120. Herbig M E, Weller K M, Merkle H P. Reviewing biophysical and cell biological methodologies in cell-penetrating peptide (CPP) research. Critical Reviews in Therapeutic Drug Carrier Systems, 2007, 24(3): 203–255
121. Shen W C. Acid-sensitive dissociation between poly(lysine) and histamine-modified poly(glutamate) as a model for drug-releasing from carriers in endosomes. Biochimica et Biophysica Acta, 1990, 1034(1): 122–124
122. Fei L, Yap L P, Conti P S, Shen W C, Zaro J L. Tumor targeting of a cell penetrating peptide by fusing with a pH-sensitive histidineglutamate co-oligopeptide. Biomaterials, 2014, 35(13): 4082–4087
123. Sun C, Shen W C, Tu J, Zaro J L. Interaction between cellpenetrating peptides and acid-sensitive anionic oligopeptides as a model for the design of targeted drug carriers. Molecular Pharmaceutics, 2014, 11(5): 1583–1590
124. Olson E S, Aguilera T A, Jiang T, Ellies L G, Nguyen Q T, Wong E H, Gross L A, Tsien R Y. In vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer. Integrative Biology: Quantitative Biosciences from Nano to Macro, 2009, 1(5–6): 382–393
125. Savariar E N, Felsen C N, Nashi N, Jiang T, Ellies L G, Steinbach P, Tsien R Y, Nguyen Q T. Real-time in vivo molecular detection of primary tumors and metastases with ratiometric activatable cellpenetrating peptides. Cancer Research, 2013, 73(2): 855–864
126. Weinstain R, Savariar E N, Felsen C N, Tsien R Y. In vivo targeting of hydrogen peroxide by activatable cell-penetrating peptides. Journal of the American Chemical Society, 2014, 136(3): 874–877
127. Lee S H, Castagner B, Leroux J C. Is there a future for cellpenetrating peptides in oligonucleotide delivery? European Journal of Pharmaceutics and Biopharmaceutics, 2013, 85(1): 5–11
128. 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. Molecular Therapy, 2009, 17(1): 95–103
129. Dubikovskaya E A, Thorne S H, Pillow T H, Contag C H, Wender P A. Overcoming multidrug resistance of small-molecule therapeutics through conjugation with releasable octaarginine transporters. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(34): 12128–12133
130. Liu H, Zhang W, Ma L, Fan L, Gao F, Ni J, Wang R. The improved blood-brain barrier permeability of endomorphin-1 using the cellpenetrating peptide synB3 with three different linkages. International Journal of Pharmaceutics, 2014, 476(1–2): 1–8
131. Hauff S J, Raju S C, Orosco R K, Gross A M, Diaz-Perez J A, Savariar E, Nashi N, Hasselman J, Whitney M, Myers J N, Lippman S M, Tsien R Y, Ideker T, Nguyen Q T. Matrixmetalloproteinases in head and neck carcinoma-cancer genome atlas analysis and fluorescence imaging in mice. Otolaryngology- Head and Neck Surgery, 2014, 151(4): 612–618
132. Gotanda Y, Wei F Y, Harada H, Ohta K, Nakamura K, Tomizawa K, Ushijima K. Efficient transduction of 11 poly-arginine peptide in an ischemic lesion of mouse brain. Journal of Stroke and Cerebrovascular Diseases, 2014, 23(8): 2023–2030
133. van Duijnhoven S M, Robillard M S, Hermann S, Kuhlmann M T, Schafers M, Nicolay K, Grull H. Imaging of MMP activity in postischemic cardiac remodeling using radiolabeled MMP-2/9 activatable peptide probes. Molecular Pharmaceutics, 2014, 11(5): 1415–1423
134. Neundorf I, Rennert R, Franke J, Kozle I, Bergmann R. Detailed analysis concerning the biodistribution and metabolism of human calcitonin-derived cell-penetrating peptides. Bioconjugate Chemistry, 2008, 19(8): 1596–1603
135. Weiss H M, Wirz B, Schweitzer A, Amstutz R, Rodriguez Perez M I, Andres H, Metz Y, Gardiner J, Seebach D. ADME investigations of unnatural peptides: Distribution of a 14C-labeled ß 3- octaarginine in rats. Chemistry & Biodiversity, 2007, 4(7): 1413–1437
136. Sehgal I, Sibrian-Vazquez M, Vicente M G. Photoinduced cytotoxicity and biodistribution of prostate cancer cell-targeted porphyrins. Journal of Medicinal Chemistry, 2008, 51(19): 6014–6020
137. Felsen C N, Savariar E N, Whitney M, Tsien R Y. Detection and monitoring of localized matrix metalloproteinase upregulation in a murine model of asthma. American Journal of Physiology. Lung Cellular and Molecular Physiology, 2014, 306(8): L764–L774
138. Michiue H, Sakurai Y, Kondo N, Kitamatsu M, Bin F, Nakajima K, Hirota Y, Kawabata S, Nishiki T, Ohmori I, Tomizawa K, Miyatake S, Ono K, Matsui H. The acceleration of boron neutron capture therapy using multi-linked mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide. Biomaterials, 2014, 35(10): 3396–3405
139. Temming R P, Eggermont L, van Eldijk M B, van Hest J C, van Delft F L. N-Terminal dual protein functionalization by strainpromoted alkyne-nitrone cycloaddition. Organic & Biomolecular Chemistry, 2013, 11(17): 2772–2779
140. Shen W C, Ryser H J. Cis-Aconityl spacer between daunomycin and macromolecular carriers: A model of pH-sensitive linkage releasing drug from a lysosomotropic conjugate. Biochemical and Biophysical Research Communications, 1981, 102(3): 1048–1054
141. Walker L, Perkins E, Kratz F, Raucher D. Cell penetrating peptides fused to a thermally targeted biopolymer drug carrier improve the delivery and antitumor efficacy of an acid-sensitive doxorubicin derivative. International Journal of Pharmaceutics, 2012, 436(1–2): 825–832
142. Nakase I, Konishi Y, Ueda M, Saji H, Futaki S. Accumulation of arginine-rich cell-penetrating peptides in tumors and the potential for anticancer drug delivery in vivo. Journal of Controlled Release, 2012, 159(2): 181–188
143. Vives E. Present and future of cell-penetrating peptide mediated delivery systems: Is the Trojan horse too wild to go only to Troy? Journal of Controlled Release, 2005, 109(1–3): 77–85
144. Vives E, Schmidt J, Pelegrin A. Cell-penetrating and cell-targeting peptides in drug delivery. Biochimica et Biophysica Acta, 2008, 1786(2): 126–138
145. Heitz F, Morris M C, Divita G. Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics. British Journal of Pharmacology, 2009, 157(2): 195–206
146. Sarko D, Beijer B, Garcia B R, Nothelfer E M, Leotta K, Eisenhut M, Altmann A, Haberkorn U, Mier W. The pharmacokinetics of cell-penetrating peptides. Molecular Pharmaceutics, 2010, 7(6): 2224–2231
147. Hamann P R, Hinman L M, Beyer C F, Lindh D, Upeslacis J, Flowers D A, Bernstein I. An anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Choice of linker. Bioconjugate Chemistry, 2002, 13(1): 40–46
148. Anderson D C, Nichols E, Manger R, Woodle D, Barry M, Fritzberg A R. Tumor cell retention of antibody Fab fragments is enhanced by an attached HIV TAT protein-derived peptide. Biochemical and Biophysical Research Communications, 1993, 194(2): 876–884
149. Trudel D, Fradet Y, Meyer F, Harel F, Tetu B. Significance of MMP-2 expression in prostate cancer: An immunohistochemical study. Cancer Research, 2003, 63(23): 8511–8515
150. Turpeenniemi-Hujanen T. Gelatinases (MMP-2 and-9) and their natural inhibitors as prognostic indicators in solid cancers. Biochimie, 2005, 87(3–4): 287–297
151. Gerweck L E, Seetharaman K. Cellular pH gradient in tumor versus normal tissue: Potential exploitation for the treatment of cancer. Cancer Research, 1996, 56(6): 1194–1198
152. Getzenberg R H, Coffey D S, De Weese T L. Hyperthermic biology and cancer therapies a hypothesis for the “Lance Armstrong effect”. Journal of the American Medical Association, 2006, 296 (4): 445–448
153. Denko N, Cairns R, Papandreou I. Overcoming physiologic barriers to cancer treatment by molecularly targeting the tumor microenvironment. Molecular Cancer Research, 2006, 4(2): 61–70
154. Crisp J L, Savariar E N, Glasgow H L, Ellies L G, Whitney M A, Tsien R Y. Dual targeting of integrin avß3 and matrix metalloproteinase-2 for optical imaging of tumors and chemotherapeutic delivery. Molecular Cancer Therapeutics, 2014, 13(6): 1514–1525
155. Nguyen Q T, Olson E S, Aguilera T A, Jiang T, Scadeng M, Ellies L G, Tsien R Y. Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(9): 4317–4322
156. van Duijnhoven S M, Robillard M S, Nicolay K, Grull H. Tumor targeting of MMP-2/9 activatable cell-penetrating imaging probes is caused by tumor-independent activation. Journal of Nuclear Medicine, 2011, 52(2): 279–286
157. Zaro J L, Fei L, Shen W C. Recombinant peptide constructs for targeted cell penetrating peptide-mediated delivery. Journal of Controlled Release, 2012, 158(3): 357–361
158. Zhu L, Kate P, Torchilin V P. Matrix metalloprotease 2-responsive multifunctional liposomal nanocarrier for enhanced tumor targeting. ACS Nano, 2012, 6(4): 3491–3498
159. Apte A, Koren E, Koshkaryev A, Torchilin V P. Doxorubicin in TAT peptide-modified multifunctional immunoliposomes demonstrates increased activity against both drug-sensitive and drugresistant ovarian cancer models. Cancer Biology & Therapy, 2014, 15(1): 69–80
160. Leader B, Baca Q J, Golan D E. Protein therapeutics: A summary and pharmacological classification. Nature Reviews. Drug Discovery, 2008, 7(1): 21–39
161. He H, Sheng J, David A E, Kwon YM, Zhang J, Huang Y, Wang J, Yang V C. The use of low molecular weight protamine chemical chimera to enhance monomeric insulin intestinal absorption. Biomaterials, 2013, 34(31): 7733–7743
162. Liang J F, Yang V C. Insulin-cell penetrating peptide hybrids with improved intestinal absorption efficiency. Biochemical and Biophysical Research Communications, 2005, 335(3): 734–738
163. Liu E, Sheng J, Ye J, Wang Y, Gong J, Yang V C, Wang J, He H. CPP mediated insulin delivery: Current status and promising future. Current Pharmaceutical Biotechnology, 2014, 15(3): 240–255
164. Fei L. Cell Penetrating Peptide-Based Drug Delivery System for Targeting Mildly Acidic pH. Dissertation for the Doctoral Degree. California: University of Southern California, 2014
165. Chen X, Zaro J L, Shen W C. Fusion protein linkers: Property, design and functionality. Advanced Drug Delivery Reviews, 2013, 65(10): 1357–1369
166. Almeida P F. Membrane-active peptides: Binding, translocation, and flux in lipid vesicles. Biochimica et Biophysica Acta, 2014, 1838(9): 2216–2227
167. Shin M C, Zhang J, Min K A, Lee K, Moon C, Balthasar J P, Yang V C. Combination of antibody targeting and PTD-mediated intracellular toxin delivery for colorectal cancer therapy. Journal of Controlled Release, 2014, 194: 197–210
168. Xu J, Xiang Q, Su J, Yang P, Zhang Q, Su Z, Xiao F, Huang Y. Evaluation of the safety and brain-related tissues distribution characteristics of TAT-HaFGF via intranasal administration. Biological & Pharmaceutical Bulletin, 2014, 37(7): 1149–1157
169. Cai S R, Xu G, Becker-Hapak M, Ma M, Dowdy S F, McLeod H L. The kinetics and tissue distribution of protein transduction in mice. European Journal of Pharmaceutical Sciences, 2006, 27(4): 311–319
170. Cerchietti L C, Yang S N, Shaknovich R, Hatzi K, Polo J M, Chadburn A, Dowdy S F, Melnick A. A peptomimetic inhibitor of BCL6 with potent antilymphoma effects in vitro and in vivo. Blood, 2009, 113(15): 3397–3405
171. Bowne W B, Michl J, Bluth M H, Zenilman M E, Pincus M R. Novel peptides from the RAS-p21 and p53 proteins for the treatment of cancer. Cancer Therapy, 2007, 5B: 331–344
172. Kwon M K, Nam J O, Park R W, Lee B H, Park J Y, Byun Y R, Kim S Y, Kwon I C, Kim I S. Antitumor effect of a transducible fusogenic peptide releasing multiple proapoptotic peptides by caspase-3. Molecular Cancer Therapeutics, 2008, 7(6): 1514–1522
173. Tan M, Lan K H, Yao J, Lu C H, Sun M, Neal C L, Lu J, Yu D. 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 Research, 2006, 66(7): 3764–3772
174. Shibata W, Maeda S, Hikiba Y, Yanai A, Ohmae T, Sakamoto K, Nakagawa H, Ogura K, Omata M. Cutting edge: The IkappaB kinase (IKK) inhibitor, NEMO-binding domain peptide, blocks inflammatory injury in murine colitis. Journal of Immunology 2007, 179(5): 2681–2685
175. Ghosh A, Roy A, Liu X, Kordower J H, Mufson E J, Hartley D M, Ghosh S, Mosley R L, Gendelman H E, Pahan K. Selective inhibition of NF-kappaB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(47): 18754–18759
176. Hotchkiss R S, McConnell KW, Bullok K, Davis C G, Chang K C, Schwulst S J, Dunne J C, Dietz G P, Bahr M, McDunn J E, Karl I E, Wagner T H, Cobb J P, Coopersmith C M, Piwnica-Worms D. TAT-BH4 and TAT-Bcl-xL peptides protect against sepsis-induced lymphocyte apoptosis in vivo. Journal of Immunology (Baltimore, MD.: 1950), 2006, 176(9): 5471–5477
177. McCusker C T, Wang Y, Shan J, Kinyanjui M W, Villeneuve A, Michael H, Fixman E D. Inhibition of experimental allergic airways disease by local application of a cell-penetrating dominantnegative STAT-6 peptide. Journal of Immunology, 2007, 179(4): 2556–2564
178. Walker L R, Ryu J S, Perkins E, McNally L R, Raucher D. Fusion of cell-penetrating peptides to thermally responsive biopolymer improves tumor accumulation of p21 peptide in a mouse model of pancreatic cancer. Drug Design, Development and Therapy, 2014, 8: 1649–1658
179. Qiu X, Johnson J R, Wilson B S, Gammon S T, Piwnica-Worms D, Barnett EM. Single-cell resolution imaging of retinal ganglion cell apoptosis in vivo using a cell-penetrating caspase-activatable peptide probe. PLoS One, 2014, 9(2): e88855
180. He X H, Yan X T, Wang Y L, Wang C Y, Zhang Z Z, Zhan J. Transduced PEP-1-heme oxygenase-1 fusion protein protects against intestinal ischemia/reperfusion injury. Journal of Surgical Research, 2014, 187(1): 77–84
181. He X H, Wang Y, Yan X T, Wang Y L, Wang C Y, Zhang Z Z, Li H, Jiang H X. Transduction of PEP-1-heme oxygenase-1 fusion protein reduces myocardial ischemia/reperfusion injury in rats. Journal of Cardiovascular Pharmacology, 2013, 62(5): 436–442
182. McCarthy H O, McCaffrey J, McCrudden CM, Zholobenko A, Ali A A, McBride J W, Massey A S, Pentlavalli S, Chen K H, Cole G, Loughran S P, Dunne N J, Donnelly R F, Kett V L, Robson T. Development and characterization of self-assembling nanoparticles using a bio-inspired amphipathic peptide for gene delivery. Journal of Controlled Release, 2014, 189: 141–149
183. Wang H, Wang H, Liang J, Jiang Y, Guo Q, Peng H, Xu Q, Huang Y. Cell-penetrating apoptotic peptide/p53 DNA nanocomplex as adjuvant therapy for drug-resistant breast cancer. Molecular Pharmaceutics, 2014, 11(10): 3352–3360
184. Hu Y, Xu B, Ji Q, Shou D, Sun X, Xu J, Gao J, Liang W. A mannosylated cell-penetrating peptide-graft-polyethylenimine as a gene delivery vector. Biomaterials, 2014, 35(13): 4236–4246
185. Wang H X, Yang X Z, Sun C Y, Mao C Q, Zhu Y H, Wang J. Matrix metalloproteinase 2-responsive micelle for siRNA delivery. Biomaterials, 2014, 35(26): 7622–7634
186. Nielsen E J, Yoshida S, Kamei N, Iwamae R, Khafagy E S, Olsen J, Rahbek U L, Pedersen B L, Takayama K, Takeda-Morishita M. Khafagyel S, Olsen J, Rahbek U L, Pedersen B L, Takayama K, Takeda-Morishita M. in vivo proof of concept of oral insulin delivery based on a co-administration strategy with the cellpenetrating peptide penetratin. Journal of Controlled Release, 2014, 189: 19–24
187. Manosroi J, Lohcharoenkal W, Gotz F, Werner R G, Manosroi W, Manosroi A. Novel application of polioviral capsid: Development of a potent and prolonged oral calcitonin using polioviral binding ligand and Tat peptide. Drug Development and Industrial Pharmacy, 2014, 40(8): 1092–1100
188. Wiethoff C M, Middaugh C R. Barriers to nonviral gene delivery. Journal of Pharmaceutical Sciences, 2003, 92(2): 203–217
189. Nam H Y, Kim J, Kim S, Yockman J W, Kim S W, Bull D A. Cell penetrating peptide conjugated bioreducible polymer for siRNA delivery. Biomaterials, 2011, 32(22): 5213–5222
190. Mo R H, Zaro J L, Shen W C. Comparison of cationic and amphipathic cell penetrating peptides for siRNA delivery and efficacy. Molecular Pharmaceutics, 2012, 9(2): 299–309
191. Margus H, Padari K, Pooga M. Cell-penetrating peptides as versatile vehicles for oligonucleotide delivery. Molecular Therapy, 2012, 20(3): 525–533
192. Amidon G L, Lee H J. Absorption of peptide and peptidomimetic drugs. Annual Review of Pharmacology and Toxicology, 1994, 34 (1): 321–341
193. Farkhani S M, Valizadeh A, Karami H, Mohammadi S, Sohrabi N, Badrzadeh F. Cell penetrating peptides: Efficient vectors for delivery of nanoparticles, nanocarriers, therapeutic and diagnostic molecules. Peptides, 2014, 57: 78–94
194. Cleal K, He L, Watson P D, Jones A T. Endocytosis, intracellular traffic and fate of cell penetrating peptide based conjugates and nanoparticles. Current Pharmaceutical Design, 2013, 19(16): 2878–2894
195. Zhang B, Zhang Y, Liao Z, Jiang T, Zhao J, Tuo Y, She X, Shen S, Chen J, Zhang Q, Jiang X, Hu Y, Pang Z. UPA-sensitive ACPPconjugated nanoparticles for multi-targeting therapy of brain glioma. Biomaterials, 2015, 36: 98–109
196. Mei L, Zhang Q, Yang Y, He Q, Gao H. Angiopep-2 and activatable cell penetrating peptide dual modified nanoparticles for enhanced tumor targeting and penetrating. International Journal of Pharmaceutics, 2014, 474(1–2): 95–102
197. Fan T, Chen C, Guo H, Xu J, Zhang J, Zhu X, Yang Y, Zhou Z, Li L, Huang Y. Design and evaluation of solid lipid nanoparticles modified with peptide ligand for oral delivery of protein drugs. European Journal of Pharmaceutics and Biopharmaceutics, 2014, 88(2): 518–528
198. Huang A, Su Z, Li S, Sun M, Xiao Y, Ping Q, Deng Y. Oral absorption enhancement of salmon calcitonin by using both Ntrimethyl chitosan chloride and oligoarginines-modified liposomes as the carriers. Drug Delivery, 2014, 21(5): 388–396
199. Gao H, Zhang S, Cao S, Yang Z, Pang Z, Jiang X. Angiopep-2 and activatable cell-penetrating peptide dual-functionalized nanoparticles for systemic glioma-targeting delivery. Molecular Pharmaceutics, 2014, 11(8): 2755–2763
200. Yang Y, Yang Y, Xie X, Cai X, Zhang H, Gong W, Wang Z, Mei X. PEGylated liposomes with NGR ligand and heat-activable cellpenetrating peptide-doxorubicin conjugate for tumor-specific therapy. Biomaterials, 2014, 35(14): 4368–4381
201. Zong T, Mei L, Gao H, Cai W, Zhu P, Shi K, Chen J, Wang Y, Gao F, He Q. Synergistic dual-ligand doxorubicin liposomes improve targeting and therapeutic efficacy of brain glioma in animals. Molecular Pharmaceutics, 2014, 11(7): 2346–2357
202. Liu Y, Ran R, Chen J, Kuang Q, Tang J, Mei L, Zhang Q, Gao H, Zhang Z, He Q. Paclitaxel loaded liposomes decorated with a multifunctional tandem peptide for glioma targeting. Biomaterials, 2014, 35(17): 4835–4847
203. Tang J, Zhang L, Liu Y, Zhang Q, Qin Y, Yin Y, Yuan W, Yang Y, Xie Y, Zhang Z, He Q. Synergistic targeted delivery of payload into tumor cells by dual-ligand liposomes co-modified with cholesterol anchored transferrin and TAT. International Journal of Pharmaceutics, 2013, 454(1): 31–40
204. Wang J, Yu Y, Yan Z, Hu Z, Li L, Li J, Jiang X, Qian Q. Anticancer activity of oncolytic adenoviruses carrying p53 is augmented by 11R in gallbladder cancer cell lines in vitro and in vivo. Oncology Reports, 2013, 30(2): 833–841
205. Tang J, Fu H, Kuang Q, Zhang L, Zhang Q, Liu Y, Ran R, Gao H, Zhang Z, He Q. Liposomes co-modified with cholesterol anchored cleavable PEG and octaarginines for tumor targeted drug delivery. Journal of Drug Targeting, 2014, 22(4): 313–326
206. Shamay Y, Shpirt L, Ashkenasy G, David A. Complexation of cellpenetrating peptide-polymer conjugates with polyanions controls cells uptake of HPMA copolymers and anti-tumor activity. Pharmaceutical Research, 2014, 31(3): 768–779
207. Wang Y, Dou L, He H, Zhang Y, Shen Q. Multifunctional nanoparticles as nanocarrier for vincristine sulfate delivery to overcome tumor multidrug resistance. Molecular Pharmaceutics, 2014, 11(3): 885–894
208. Nakamura T, Yamazaki D, Yamauchi J, Harashima H. The nanoparticulation by octaarginine-modified liposome improves alpha-galactosylceramide-mediated antitumor therapy via systemic administration. Journal of Controlled Release, 2013, 171(2): 216–224