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Cancer targeting peptides

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Abstract

Despite continuing advances in the development of biomacromolecules for therapeutic purposes, successful application of these often large and hydrophilic molecules has been hindered by their inability to efficiently traverse the cellular plasma membrane. In recent years, cell-penetrating peptides (CPPs) have received considerable attention as a promising class of delivery vectors due to their ability to mediate the efficient import of a large number of cargoes in vitro and in vivo. However, the lack of target specificity of CPPs remains a major obstacle to their clinical development. To address this issue, researchers have developed strategies in which chemotherapeutic drugs are conjugated to cancer targeting peptides (CTPs) that exploit the unique characteristics of the tumor microenvironment or cancer cells, thereby improving cancer cell specificity. This review highlights several of these strategies that are currently in use, and discusses how multi-component nanoparticles conjugated to CTPs can be designed to provide a more efficient cancer therapeutic delivery strategy.

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References

  1. Juliano R (2007) Challenges to macromolecular drug delivery. Portland Press Limited, London

    Book  Google Scholar 

  2. Bolhassani A (2011) Potential efficacy of cell-penetrating peptides for nucleic acid and drug delivery in cancer. Biochim Biophys Acta (BBA) Rev Cancer 1816(2):232–246

    Article  CAS  Google Scholar 

  3. McErlean EM, McCrudden CM, McCarthy HO (2015) Multifunctional delivery systems for cancer gene therapy. In: Hashad D (ed) Gene therapy—principles and challenges. InTech, London

    Google Scholar 

  4. Regberg J, Srimanee A, Langel Ü (2012) Applications of cell-penetrating peptides for tumor targeting and future cancer therapies. Pharmaceuticals 5(9):991–1007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Magzoub M, Gräslund A (2004) Cell-penetrating peptides: small from inception to application. Q Rev Biophys 37(2):147–195

    Article  CAS  PubMed  Google Scholar 

  6. Reissmann S (2014) Cell penetration: scope and limitations by the application of cell-penetrating peptides. J Pept Sci 20(10):760–784

    Article  CAS  PubMed  Google Scholar 

  7. Derossi D et al (1994) The third helix of the Antennapedia homeodomain translocates through biological membranes. J Biol Chem 269(14):10444–10450

    CAS  PubMed  Google Scholar 

  8. Vives 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(25):16010–16017

    Article  CAS  PubMed  Google Scholar 

  9. Zorko M, Langel Ü (2005) Cell-penetrating peptides: mechanism and kinetics of cargo delivery. Adv Drug Deliv Rev 57(4):529–545

    Article  CAS  PubMed  Google Scholar 

  10. Snyder EL, Dowdy SF (2004) Cell penetrating peptides in drug delivery. Pharm Res 21(3):389–393

    Article  CAS  PubMed  Google Scholar 

  11. Schwarze SR et al (1999) In vivo protein transduction: delivery of a biologically active protein into the mouse. Science 285(5433):1569–1572

    Article  CAS  PubMed  Google Scholar 

  12. Josephson L et al (1999) High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates. Bioconjug Chem 10(2):186–191

    Article  CAS  PubMed  Google Scholar 

  13. Jiang Q-Y et al (2011) Gene delivery to tumor cells by cationic polymeric nanovectors coupled to folic acid and the cell-penetrating peptide octaarginine. Biomaterials 32(29):7253–7262

    Article  CAS  PubMed  Google Scholar 

  14. Asai T et al (2014) Cell-penetrating peptide-conjugated lipid nanoparticles for siRNA delivery. Biochem Biophys Res Commun 444(4):599–604

    Article  CAS  PubMed  Google Scholar 

  15. Lehto T, Kurrikoff K, Langel Ü (2012) Cell-penetrating peptides for the delivery of nucleic acids. Expert Opin Drug Deliv 9(7):823–836

    Article  CAS  PubMed  Google Scholar 

  16. Juliano RL et al (2009) Cell-targeting and cell-penetrating peptides for delivery of therapeutic and imaging agents. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1(3):324–335

    Article  CAS  PubMed  Google Scholar 

  17. Bechara C, Sagan S (2013) Cell-penetrating peptides: 20 years later, where do we stand? FEBS Lett 587(12):1693–1702

    Article  CAS  PubMed  Google Scholar 

  18. Raucher D, Ryu JS (2015) Cell-penetrating peptides: strategies for anticancer treatment. Trends Mol Med 21(9):560–570

    Article  CAS  PubMed  Google Scholar 

  19. Foged C, Nielsen HM (2008) Cell-penetrating peptides for drug delivery across membrane barriers. Expert Opin Drug Deliv 5(1):105–117

    Article  CAS  PubMed  Google Scholar 

  20. Subrizi A et al (2012) Tat (48-60) peptide amino acid sequence is not unique in its cell penetrating properties and cell-surface glycosaminoglycans inhibit its cellular uptake. J Control Release 158(2):277–285

    Article  CAS  PubMed  Google Scholar 

  21. Åmand HL et al (2008) Stimulated endocytosis in penetratin uptake: effect of arginine and lysine. Biochem Biophys Res Commun 371(4):621–625

    Article  CAS  PubMed  Google Scholar 

  22. Mitchell DJ et al (2000) Polyarginine enters cells more efficiently than other polycationic homopolymers. J Pept Res 56(5):318–325

    Article  CAS  PubMed  Google Scholar 

  23. Kalafatovic D, Giralt E (2017) Cell-penetrating peptides: design strategies beyond primary structure and amphipathicity. Molecules 22(11):1929

    Article  CAS  PubMed Central  Google Scholar 

  24. Franz J et al (2016) SAP (E)—a cell-penetrating polyproline helix at lipid interfaces. Biochim Biophys Acta (BBA) Biomembr 1858(9):2028–2034

    Article  CAS  Google Scholar 

  25. Kristensen M, Birch D, Mørck Nielsen H (2016) Applications and challenges for use of cell-penetrating peptides as delivery vectors for peptide and protein cargos. Int J Mol Sci 17(2):185

    Article  CAS  PubMed Central  Google Scholar 

  26. Rydberg HA et al (2012) Effects of tryptophan content and backbone spacing on the uptake efficiency of cell-penetrating peptides. Biochemistry 51(27):5531–5539

    Article  CAS  PubMed  Google Scholar 

  27. Borrelli A et al (2018) Cell penetrating peptides as molecular carriers for anti-cancer agents. Molecules 23(2):295

    Article  CAS  PubMed Central  Google Scholar 

  28. Rydström A et al (2011) Direct translocation as major cellular uptake for CADY self-assembling peptide-based nanoparticles. PLoS One 6(10):e25924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Guo Z et al (2016) Cell-penetrating peptides: possible transduction mechanisms and therapeutic applications. Biomed Rep 4(5):528–534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Simeoni F et al (2003) Insight into the mechanism of the peptide-based gene delivery system MPG: implications for delivery of siRNA into mammalian cells. Nucleic Acids Res 31(11):2717–2724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Copolovici DM et al (2014) Cell-penetrating peptides: design, synthesis, and applications. ACS Nano 8(3):1972–1994

    Article  CAS  PubMed  Google Scholar 

  32. Avci F, Sariyar Akbulut B, Ozkirimli E (2018) Membrane active peptides and their biophysical characterization. Biomolecules 8(3):77

    Article  CAS  PubMed Central  Google Scholar 

  33. Mussbach F et al (2011) Transduction of peptides and proteins into live cells by cell penetrating peptides. J Cell Biochem 112(12):3824–3833

    Article  CAS  PubMed  Google Scholar 

  34. Brock R (2014) The uptake of arginine-rich cell-penetrating peptides: putting the puzzle together. Bioconjug Chem 25(5):863–868

    Article  CAS  PubMed  Google Scholar 

  35. Vivès E, Schmidt J, Pèlegrin A (2008) Cell-penetrating and cell-targeting peptides in drug delivery. Biochim Biophys Acta (BBA) Rev Cancer 1786(2):126–138

    Article  CAS  Google Scholar 

  36. LeCher JC, Nowak SJ, McMurry JL (2017) Breaking in and busting out: cell-penetrating peptides and the endosomal escape problem. Biomol Concepts 8(3–4):131–141

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Jiang T et al (2004) Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proc Natl Acad Sci USA 101(51):17867–17872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Huang S et al (2013) Tumor targeting and microenvironment-responsive nanoparticles for gene delivery. Biomaterials 34(21):5294–5302

    Article  CAS  PubMed  Google Scholar 

  39. Jiang B (2017) Aerobic glycolysis and high level of lactate in cancer metabolism and microenvironment. Genes Dis 4(1):25–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Nguyen VP et al (2015) A novel soluble peptide with pH-responsive membrane insertion. Biochemistry 54(43):6567–6575

    Article  CAS  PubMed  Google Scholar 

  41. Gao W, Chan JM, Farokhzad OC (2010) pH-responsive nanoparticles for drug delivery. Mol Pharm 7(6):1913–1920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Daumar P et al (2012) Efficient 18F-labeling of large 37-amino-acid pHLIP peptide analogues and their biological evaluation. Bioconjug Chem 23(8):1557–1566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Reshetnyak YK et al (2011) Measuring tumor aggressiveness and targeting metastatic lesions with fluorescent pHLIP. Mol Imaging Biol 13(6):1146–1156

    Article  PubMed  PubMed Central  Google Scholar 

  44. Vāvere AL et al (2009) A novel technology for the imaging of acidic prostate tumors by positron emission tomography. Can Res 69(10):4510–4516

    Article  CAS  Google Scholar 

  45. Karabadzhak AG et al (2014) pHLIP-FIRE, a cell insertion-triggered fluorescent probe for imaging tumors demonstrates targeted cargo delivery in vivo. ACS Chem Biol 9(11):2545–2553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. An M et al (2010) pH-(low)-insertion-peptide (pHLIP) translocation of membrane impermeable phalloidin toxin inhibits cancer cell proliferation. Proc Natl Acad Sci 107(47):20246–20250

    Article  PubMed  PubMed Central  Google Scholar 

  47. Moshnikova A et al (2013) Antiproliferative effect of pHLIP-amanitin. Biochemistry 52(7):1171–1178

    Article  CAS  PubMed  Google Scholar 

  48. Reshetnyak YK et al (2006) Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix. Proc Natl Acad Sci 103(17):6460–6465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hunt JF et al (1997) Spontaneous, pH-dependent membrane insertion of a transbilayer α-helix. Biochemistry 36(49):15177–15192

    Article  CAS  PubMed  Google Scholar 

  50. Andreev OA, Engelman DM, Reshetnyak YK (2014) Targeting diseased tissues by pHLIP insertion at low cell surface pH. Front Physiol 5:1–7

    Article  Google Scholar 

  51. Yao L et al (2013) pHLIP peptide targets nanogold particles to tumors. Proc Natl Acad Sci 110(2):465–470

    Article  PubMed  Google Scholar 

  52. Andreev OA, Engelman DM, Reshetnyak YK (2009) Targeting acidic diseased tissue: new technology based on use of the pH (Low) Insertion Peptide (pHLIP). Chim Oggi 27(2):34

    PubMed  PubMed Central  Google Scholar 

  53. Andreev OA, Engelman DM, Reshetnyak YK (2010) pH-sensitive membrane peptides (pHLIPs) as a novel class of delivery agents. Mol Membr Biol 27(7):341–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Deacon JC, Engelman DM, Barrera FN (2015) Targeting acidity in diseased tissues: mechanism and applications of the membrane-inserting peptide, pHLIP. Arch Biochem Biophys 565:40–48

    Article  CAS  PubMed  Google Scholar 

  55. Zoonens M, Reshetnyak YK, Engelman DM (2008) Bilayer interactions of pHLIP, a peptide that can deliver drugs and target tumors. Biophys J 95(1):225–235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wei Y et al (2017) pH-responsive pHLIP (pH low insertion peptide) nanoclusters of superparamagnetic iron oxide nanoparticles as a tumor-selective MRI contrast agent. Acta Biomater 55:194–203

    Article  CAS  PubMed  Google Scholar 

  57. Wyatt LC, Lewis JS, Andreev OA, Reshetnyak YK, Engelman DM (2017) Applications of pHLIP technology for cancer imaging and therapy. Trends Biotechnol 35(7):653–664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Weerakkody D et al (2013) Family of pH (low) insertion peptides for tumor targeting. Proc Natl Acad Sci 110(15):5834–5839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Reshetnyak YK et al (2008) Energetics of peptide (pHLIP) binding to and folding across a lipid bilayer membrane. Proc Natl Acad Sci 105(40):15340–15345

    Article  PubMed  PubMed Central  Google Scholar 

  60. Wijesinghe D et al (2013) pH dependent transfer of nano-pores into membrane of cancer cells to induce apoptosis. Sci Rep 3:3560

    Article  PubMed  PubMed Central  Google Scholar 

  61. Song Q et al (2016) A smart tumor targeting peptide–drug conjugate, pHLIP-SS-DOX: synthesis and cellular uptake on MCF-7 and MCF-7/Adr cells. Drug Deliv 23(5):1734–1746

    CAS  PubMed  Google Scholar 

  62. Kyrychenko A (2015) NANOGOLD decorated by pHLIP peptide: comparative force field study. Phys Chem Chem Phys 17(19):12648–12660

    Article  CAS  PubMed  Google Scholar 

  63. Anderson MD (2015) Development of new tools for study of tumor microenvironment. Open access Dissertations. Paper 359

  64. Demoin DW et al (2016) PET imaging of extracellular pH in tumors with 64Cu-and 18F-labeled pHLIP peptides: a structure–activity optimization study. Bioconjug Chem 27(9):2014–2023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Andreev OA et al (2010) pH (low) insertion peptide (pHLIP) inserts across a lipid bilayer as a helix and exits by a different path. Proc Natl Acad Sci 107(9):4081–4086

    Article  PubMed  PubMed Central  Google Scholar 

  66. Karabadzhak AG et al (2012) Modulation of the pHLIP transmembrane helix insertion pathway. Biophys J 102(8):1846–1855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Shu NS et al (2015) Residue-specific structures and membrane locations of pH-low insertion peptide by solid-state nuclear magnetic resonance. Nat Commun 6:1–10

    Article  CAS  Google Scholar 

  68. Hanz SZ et al (2016) Protonation-driven membrane insertion of a pH-low insertion peptide. Angew Chem Int Ed 55(40):12376–12381

    Article  CAS  Google Scholar 

  69. Narayanan T et al (2016) pHLIP peptide interaction with a membrane monitored by SAXS. J Phys Chem B 120(44):11484–11491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Daniels JL et al (2017) Synthesis and characterization of pHLIP® coated gold nanoparticles. Biochem Biophys Rep 10:62–69

    PubMed  PubMed Central  Google Scholar 

  71. Scott HL et al (2015) The negative charge of the membrane has opposite effects on the membrane entry and exit of pH-low insertion peptide. Biochemistry 54(9):1709–1712

    Article  CAS  PubMed  Google Scholar 

  72. Gupta C, Mertz B (2017) Protonation Enhances the Inherent Helix-Forming Propensity of pHLIP. ACS Omega 2(11):8536–8542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Sosunov EA et al (2013) pH (low) insertion peptide (pHLIP) targets ischemic myocardium. Proc Natl Acad Sci 110(1):82–86

    Article  PubMed  Google Scholar 

  74. Van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9(2):112–124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Vasquez-Montes V et al (2018) Comparison of lipid-dependent bilayer insertion of pHLIP and its P20G variant. Biochim Biophys Acta (BBA) Biomembr 1860(2):534–543

    Article  CAS  Google Scholar 

  76. Kyrychenko A et al (2015) Lipid headgroups modulate membrane insertion of pHLIP peptide. Biophys J 108(4):791–794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wyatt LC et al (2018) Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors. Proc Natl Acad Sci 115(12):E2811–E2818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Petrova V et al (2018) The hypoxic tumour microenvironment. Oncogenesis 7(1):10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kim Y et al (2009) Hypoxic tumor microenvironment and cancer cell differentiation. Curr Mol Med 9(4):425–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Majmundar AJ, Wong WJ, Simon MC (2010) Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell 40(2):294–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Harada H, Hiraoka M, Kizaka-Kondoh S (2002) Antitumor effect of TAT-oxygen-dependent degradation-caspase-3 fusion protein specifically stabilized and activated in hypoxic tumor cells. Can Res 62(7):2013–2018

    CAS  Google Scholar 

  82. Nalla AK et al (2010) Targeting MMP-9, uPAR, and cathepsin B inhibits invasion, migration and activates apoptosis in prostate cancer cells. Cancer Gene Ther 17(9):599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Polette M et al (2004) Tumour invasion and matrix metalloproteinases. Crit Rev Oncol Hematol 49(3):179–186

    Article  PubMed  Google Scholar 

  84. Weidle UH, Tiefenthaler G, Georges G (2014) Proteases as activators for cytotoxic prodrugs in antitumor therapy. Cancer Genom Proteom 11(2):67–79

    Google Scholar 

  85. Olson ES et al (2009) In vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer. Integr Biol 1(5–6):382–393

    Article  CAS  Google Scholar 

  86. Hofmann H-S et al (2005) Matrix metalloproteinase-12 expression correlates with local recurrence and metastatic disease in non-small cell lung cancer patients. Clin Cancer Res 11(3):1086–1092

    CAS  PubMed  Google Scholar 

  87. Gong Y, Chippada-Venkata UD, Oh WK (2014) Roles of matrix metalloproteinases and their natural inhibitors in prostate cancer progression. Cancers 6(3):1298–1327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. van Duijnhoven SM et al (2011) Tumor targeting of MMP-2/9 activatable cell-penetrating imaging probes is caused by tumor-independent activation. J Nucl Med 52(2):279–286

    Article  CAS  PubMed  Google Scholar 

  89. Aguilera TA et al (2009) Systemic in vivo distribution of activatable cell penetrating peptides is superior to that of cell penetrating peptides. Integr Biol 1(5–6):371–381

    Article  CAS  Google Scholar 

  90. Anderson CF, Cui H (2017) Protease-sensitive nanomaterials for cancer therapeutics and imaging. Ind Eng Chem Res 56(20):5761–5777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Shi N-Q et al (2012) Enhancing cellular uptake of activable cell-penetrating peptide–doxorubicin conjugate by enzymatic cleavage. Int J Nanomed 7:1613

    CAS  Google Scholar 

  92. Jiang T et al (2004) Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proc Natl Acad Sci 101(51):17867–17872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Nguyen QT et al (2010) Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival. Proc Natl Acad Sci 107(9):4317–4322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Malhotra M et al (2013) Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA. Int J Nanomed 8:2041

    Article  CAS  Google Scholar 

  95. Lee SH et al (2014) Activatable cell penetrating peptide–peptide nucleic acid conjugate via reduction of azobenzene PEG chains. J Am Chem Soc 136(37):12868–12871

    Article  CAS  PubMed  Google Scholar 

  96. Wender PA et al (2000) The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: peptoid molecular transporters. Proc Natl Acad Sci 97(24):13003–13008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Jin E et al (2013) Acid-active cell-penetrating peptides for in vivo tumor-targeted drug delivery. J Am Chem Soc 135(2):933–940

    Article  CAS  PubMed  Google Scholar 

  98. Bode SA et al (2015) Enzyme-activatable cell-penetrating peptides through a minimal side chain modification. Bioconjug Chem 26(5):850–856

    Article  CAS  PubMed  Google Scholar 

  99. Vocero-Akbani AM et al (1999) Killing HIV-infected cells by transduction with an HIV protease-activated caspase-3 protein. Nat Med 5(1):29

    Article  CAS  PubMed  Google Scholar 

  100. Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324(5930):1029–1033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Mathupala S, Ko YA, Pedersen P (2006) Hexokinase II: cancer’s double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene 25(34):4777–4786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Arzoine L et al (2009) Voltage-dependent anion channel 1-based peptides interact with hexokinase to prevent its anti-apoptotic activity. J Biol Chem 284(6):3946–3955

    Article  CAS  PubMed  Google Scholar 

  103. Woldetsadik AD et al (2017) Hexokinase II–derived cell-penetrating peptide targets mitochondria and triggers apoptosis in cancer cells. FASEB J 31(5):2168–2184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Pastorino JG, Shulga N, Hoek JB (2002) Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J Biol Chem 277(9):7610–7618

    Article  CAS  PubMed  Google Scholar 

  105. Patra KC et al (2013) Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer. Cancer Cell 24(2):213–228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Rezgui R et al (2016) Precise quantification of cellular uptake of cell-penetrating peptides using fluorescence-activated cell sorting and fluorescence correlation spectroscopy. Biochim Biophys Acta (BBA) Biomembr 1858(7):1499–1506

    Article  CAS  Google Scholar 

  107. Takayama K et al (2012) Effect of the attachment of a penetration accelerating sequence and the influence of hydrophobicity on octaarginine-mediated intracellular delivery. Mol Pharm 9(5):1222–1230

    Article  CAS  PubMed  Google Scholar 

  108. Kondo E et al (2012) Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems. Nat Commun 3:951

    Article  CAS  PubMed  Google Scholar 

  109. Shi J et al (2017) Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 17(1):20

    Article  CAS  PubMed  Google Scholar 

  110. Zuo HD et al (2014) The effect of superparamagnetic iron oxide with iRGD peptide on the labeling of pancreatic cancer cells in vitro: a preliminary study. BioMed Res Int 2014:1–8

    Google Scholar 

  111. Shirazi AN et al (2014) Cyclic peptide-capped gold nanoparticles for enhanced siRNA delivery. Molecules 19(9):13319–13331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Li H, Tsui T, Ma W (2015) Intracellular delivery of molecular cargo using cell-penetrating peptides and the combination strategies. Int J Mol Sci 16(8):19518–19536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Qin H et al (2017) Tumor microenvironment targeting and responsive peptide-based nanoformulations for improved tumor therapy. Mol Pharmacol. 1:1. https://doi.org/10.1124/mol.116.108084

    Article  CAS  Google Scholar 

  114. Yoo J et al (2017) Protease-activatable cell-penetrating peptide possessing ROS-triggered phase transition for enhanced cancer therapy. J Control Release 264:89–101

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Professor David Male (The Open University) for critical reading of the manuscript. This work was supported by funding from NYU Abu Dhabi (Research Grant) and an ADEK Award for Research Excellence Grant (AARE17-089) to M.M.

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  1. Biology Program, New York University Abu Dhabi, PO Box 129188, Saadiyat Island Campus, Abu Dhabi, United Arab Emirates

    Mona Kalmouni, Sumaya Al-Hosani & Mazin Magzoub

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  1. Mona Kalmouni
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Kalmouni, M., Al-Hosani, S. & Magzoub, M. Cancer targeting peptides. Cell. Mol. Life Sci. 76, 2171–2183 (2019). https://doi.org/10.1007/s00018-019-03061-0

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