RGD Peptide as a Targeting Moiety for Theranostic Purpose: An Update Study

  • Saket Asati
  • Vikas Pandey
  • Vandana SoniEmail author


In the current scenario, the utility of peptide as the targeting ligand has been increased for the efficient diagnosis and treatment of tumor cells. Blood vessels of tumor cells show some molecular receptors on the endothelial cell surface which can differentiate these cells from the remaining vasculature of other normal cells and tissues. Thus, these molecular receptors functioned as the revolutionary and striking target for the effective cancer diagnosis and treatment. Integrin (αvβ3) receptors are highly overexpressed onto the tumor neovasculature and tumor cells. Arginine-Glycine-Aspartic (RGD) peptide may be attached to these overexpressed integrin receptors with high affinity. Therefore, RGD-based systems have been developed for the effective delivery of diagnostic agent and anticancer drug for the diagnosis and treatment of cancer cells, respectively. In this review, an overview of peptide based nanoparticle especially RGD based nanoparticle systems in the field of theranostic application is provided.

Graphical Abstract


αvβ3 integrin Angiogenesis Radiolabeled peptide RGD peptide Theranostic Tumor vasculature 


Compliance with Ethical Standards

Conflict of interest

The authors declare no competing financial interest.


  1. Adams GP, Weiner LM (2005) Monoclonal antibody therapy of cancer. Nat Biotechnol 23:1147–1157CrossRefPubMedGoogle Scholar
  2. Allen TM, Cullis PR (2004) Drug delivery systems: entering the mainstream. Science 303:1818–1832CrossRefPubMedGoogle Scholar
  3. Amin M, Mansourian M, Koning GA, Badiee A, Jaafari MR, Ten Hagen TL (2015) Development of a novel cyclic RGD peptide for multiple targeting approaches of liposomes to tumor region. J Control Release 220:308–315CrossRefPubMedGoogle Scholar
  4. Anuradha C, Kanno S, Hirano S (2000) RGD peptide-induced apoptosis in human leukemia HL-60 cells requires caspase-3 activation. Cell Biol Toxicol 16:275–283CrossRefPubMedGoogle Scholar
  5. Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279:377–380CrossRefPubMedGoogle Scholar
  6. Baggio LL, Drucker DJ (2014) Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight. J Clin Invest 124:4223–4226CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bansal D, Yadav K, Pandey V, Ganeshpurkar A, Agnihotri A, Dubey N (2016) Lactobionic acid coupled liposomes: an innovative strategy for targeting hepatocellular carcinoma. Drug Deliv 23:140–146CrossRefPubMedGoogle Scholar
  8. Bellis SL (2011) Advantages of RGD peptides for directing cell association with biomaterials. Biomaterials 32:4205–4210CrossRefPubMedPubMedCentralGoogle Scholar
  9. Béraud-Dufour S, Devader C, Massa F, Roulot M, Coppola T, Mazella J (2016) Focal adhesion kinase-dependent role of the soluble form of neurotensin receptor-3/sortilin in colorectal cancer cell dissociation. Int J Mol Sci 17:1860CrossRefPubMedCentralGoogle Scholar
  10. Borgman MP, Aras O, Geyser-Stoops S, Sausville EA, Ghandehari H (2009) Biodistribution of HPMA copolymer-aminohexylgeldanamycin-RGDfK conjugates for prostate cancer drug delivery. Mol Pharm 6:1836–1847CrossRefPubMedPubMedCentralGoogle Scholar
  11. Brown KC (2010) Peptidic tumor targeting agents: the road from phage display peptide selections to clinical applications. Curr Pharm Des 16:1040–1054CrossRefPubMedPubMedCentralGoogle Scholar
  12. Byrne JD, Betancourt T, Brannon-Peppas L (2008) Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev 60:1615–1626CrossRefPubMedGoogle Scholar
  13. Chavakis E, Riecke B, Lin J, Linn T, Bretzel R, Preissner K, Brownlee M, Hammes HP (2002) Kinetics of integrin expression in the mouse model of proliferative retinopathy and success of secondary intervention with cyclic RGD peptides. Diabetologia 45:262–267CrossRefPubMedGoogle Scholar
  14. Chen Y, Xu X, Hong S, Chen J, Liu N, Underhill CB, Creswell K, Zhang L (2001) RGD-tachyplesin inhibits tumor growth. Cancer Res 61:2434–2438PubMedGoogle Scholar
  15. Chen J, Bly R, Saad M, AlKhodary M, El-Backly R, Cohen D, Kattamis N, Fatta M, Moore W, Arnold C (2011) In vivo study of adhesion and bone growth around implanted laser groove/RGD-functionalized Ti-6Al-4V pins in rabbit femurs. Mater Sci Eng 31:826–832CrossRefGoogle Scholar
  16. Choi N, Kim SM, Hong KS, Cho G, Cho JH, Lee C, Ryu EK (2011) The use of the fusion protein RGD-HSA-TIMP2 as a tumor targeting imaging probe for SPECT and PET. Biomaterials 32:7151–7158CrossRefPubMedGoogle Scholar
  17. Colombo M, Bianchi A (2010) Click chemistry for the synthesis of RGD-containing integrin ligands. Molecules 15:178–197CrossRefPubMedPubMedCentralGoogle Scholar
  18. Coppage R, Slocik JM, Briggs BD, Frenkel AI, Naik RR, Knecht MR (2012) Determining peptide sequence effects that control the size, structure, and function of nanoparticles. ACS Nano 6:1625–1636CrossRefPubMedGoogle Scholar
  19. Corti A, Curnis F, Arap W, Pasqualini R (2008) The neovasculature homing motif NGR: more than meets the eye. Blood 112:2628–2635CrossRefPubMedPubMedCentralGoogle Scholar
  20. Cui H, Webber MJ, Stupp SI (2010) Self-assembly of peptide amphiphiles: from molecules to nanostructures to biomaterials. Biopolymers 94:1–18CrossRefPubMedPubMedCentralGoogle Scholar
  21. Curnis F, Gasparri A, Sacchi A, Longhi R, Corti A (2004) Coupling tumor necrosis factor-alpha with alphaV integrin ligands improves its antineoplastic activity. Cancer Res 64:565–571CrossRefPubMedGoogle Scholar
  22. Danhier F, Feron O, Préat V (2010) To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release 148:135–146CrossRefPubMedGoogle Scholar
  23. Deming TJ (2005) Polypeptide hydrogels via a unique assembly mechanism. Soft Matter 1:28–35CrossRefGoogle Scholar
  24. Deming TJ (2010) Regenerative medicine: noodle gels for cells. Nat Mater 9:535–536CrossRefPubMedGoogle Scholar
  25. Deutscher SL (2010) Phage display in molecular imaging and diagnosis of cancer. Chem Rev 110:3196–3211CrossRefPubMedPubMedCentralGoogle Scholar
  26. Dickerson EB, Akhtar N, Steinberg H, Wang ZY, Lindstrom MJ, Padilla ML, Auerbach R, Helfand SC (2004) Enhancement of the antiangiogenic activity of interleukin-12 by peptide targeted delivery of the cytokine to alphavbeta3 integrin. Mol Cancer Res 2:663–673PubMedGoogle Scholar
  27. Eliceiri BP, Cheresh DA (1999) The role of alpha v integrins during angiogenesis: insights into potential mechanisms of action and clinical development. J Clin Invest 103:1227–1230CrossRefPubMedPubMedCentralGoogle Scholar
  28. El-Sayed NS, Shirazi AN, El-Meligy MG, El-Ziaty AK, Nagieb ZA, Parang K, Tiwari RK (2016) Design, synthesis, and evaluation of chitosan conjugated GGRGDSK peptides as a cancer cell targeting molecular transporter. Int J Biol Macromol 87:611–622CrossRefPubMedGoogle Scholar
  29. Fairbrother WJ, Christinger HW, Cochran AG, Fuh G, Keenan CJ, Quan C, Shriver SK, Tom JY, Wells JA, Cunningham BC (1998) Novel peptides selected to bind vascular endothelial growth factor target the receptor-binding site. Biochemistry 37:17754–17764CrossRefPubMedGoogle Scholar
  30. Fang Y, Jiang Y, Zou Y, Meng F, Zhang J, Deng C, Sun H, Zhong Z (2017a) Targeted glioma chemotherapy by cyclic RGD peptide-functionalized reversibly core-crosslinked multifunctional poly (ethylene glycol)-b-poly (ε-caprolactone) micelles. Acta Biomater 50:396–406CrossRefPubMedGoogle Scholar
  31. Fang Z, Sun Y, Xiao H, Li P, Liu M, Ding F, Kan W, Miao R (2017b) Targeted osteosarcoma chemotherapy using RGD peptide-installed doxorubicin-loaded biodegradable polymeric micelle. Biomed Pharmacother 85:160–168CrossRefPubMedGoogle Scholar
  32. Fei W, Zhang Y, Han S, Tao J, Zheng H, Wei Y, Zhu J, Li F, Wang X (2017) RGD conjugated liposome-hollow silica hybrid nanovehicles for targeted and controlled delivery of arsenic trioxide against hepatic carcinoma. Int J Pharm 519:250–262CrossRefPubMedGoogle Scholar
  33. Fox ME, Szoka FC, Fréchet JM (2009) Soluble polymer carriers for the treatment of cancer: the importance of molecular architecture. Acc Chem Res 42:1141–1151CrossRefPubMedPubMedCentralGoogle Scholar
  34. Frochot C, Di Stasio B, Vanderesse R, Belgy MJ, Dodeller M, Guillemin F, Viriot ML, Barberi-Heyob M (2007) Interest of RGD-containing linear or cyclic peptide targeted tetraphenylchlorin as novel photosensitizers for selective photodynamic activity. Bioorg Chem 35:205–220CrossRefPubMedGoogle Scholar
  35. Fu X, Yang Y, Li X, Lai H, Huang Y, He L, Zheng W, Chen T (2016) RGD peptide-conjugated selenium nanoparticles: antiangiogenesis by suppressing VEGF-VEGFR2-ERK/AKT pathway. Nanomed Nanotechnol Biol Med 12:1627–1639CrossRefGoogle Scholar
  36. García AJ (2005) Get a grip: integrins in cell-biomaterial interactions. Biomaterials 26:7525–7529CrossRefPubMedGoogle Scholar
  37. Gentilucci L, De Marco R, Cerisoli L (2010) Chemical modifications designed to improve peptide stability: incorporation of non-natural amino acids, pseudo-peptide bonds, and cyclization. Curr Pharm Des 16:3185–3203CrossRefPubMedGoogle Scholar
  38. Gil ES, Mandal BB, Park SH, Marchant JK, Omenetto FG, Kaplan DL (2010) Helicoidal multi-lamellar features of RGD-functionalized silk biomaterials for corneal tissue engineering. Biomaterials 31:8953–8963CrossRefPubMedPubMedCentralGoogle Scholar
  39. Gilad Y, Noy E, Senderowitz H, Albeck A, Firer MA, Gellerman G (2016) Synthesis, biological studies and molecular dynamics of new anticancer RGD-based peptide conjugates for targeted drug delivery. Bioorg Med Chem 24:294–303CrossRefPubMedGoogle Scholar
  40. Guo Z, He B, Jin H, Zhang H, Dai W, Zhang L, Zhang H, Wang X, Wang J, Zhang X, Zhang Q (2014) Targeting efficiency of RGD-modified nanocarriers with different ligand intervals in response to integrin αvβ3 clustering. Biomaterials 35:6106–6117CrossRefPubMedGoogle Scholar
  41. Haedicke K, Brand C, Omar M, Ntziachristos V, Reiner T, Grimm J (2017) Sonophore labeled RGD: a targeted contrast agent for optoacoustic imaging. Photoacoustics 6:1–8CrossRefPubMedPubMedCentralGoogle Scholar
  42. Hatakeyama S, Sugihara K, Shibata TK, Nakayama J, Akama TO, Tamura N, Wong SM, Bobkov AA, Takano Y, Ohyama C, Fukuda M (2011) Targeted drug delivery to tumor vasculature by a carbohydrate mimetic peptide. Proc Natl Acad Sci USA 108:19587–19592CrossRefPubMedGoogle Scholar
  43. Haubner R, Wester HJ (2004) Radiolabeled tracers for imaging of tumor angiogenesis and evaluation of anti-angiogenic therapies. Curr Pharm Des 10:1439–1455CrossRefPubMedGoogle Scholar
  44. Hennessy KM, Clem WC, Phipps MC, Sawyer AA, Shaikh FM, Bellis SL (2008) The effect of RGD peptides on osseointegration of hydroxyapatite biomaterials. Biomaterials 29:3075–3083CrossRefPubMedPubMedCentralGoogle Scholar
  45. Hilgenbrink AR, Low PS (2005) Folate receptor-mediated drug targeting: from therapeutics to diagnostics. J Pharm Sci 94:2135–2146CrossRefPubMedGoogle Scholar
  46. Hood JD, Bednarski M, Frausto R, Guccione S, Reisfeld RA, Xiang R, Cheresh DA (2002) Tumor regression by targeted gene delivery to the neovasculature. Science 296:2404–2407CrossRefPubMedGoogle Scholar
  47. Hou J, Diao Y, Li W, Yang Z, Zhang L, Chen Z, Wu Y (2016) RGD peptide conjugation results in enhanced antitumor activity of PD0325901 against glioblastoma by both tumor-targeting delivery and combination therapy. Int J Pharm 505:329–340CrossRefPubMedGoogle Scholar
  48. Huang Y, Liu W, Gao F, Fang X, Chen Y (2016) c(RGDyK)-decorated pluronic micelles for enhanced doxorubicin and paclitaxel delivery to brain glioma. Int J Nanomed 11:1629–1641Google Scholar
  49. Humphries JD, Byron A, Humphries MJ (2006) Integrin ligands at a glance. J Cell Sci 119:3901–3903CrossRefPubMedPubMedCentralGoogle Scholar
  50. Hutmacher DW (2010) Biomaterials offer cancer research the third dimension. Nat Mater 9:90–93CrossRefPubMedGoogle Scholar
  51. Hwang DS, Sim SB, Cha HJ (2007) Cell adhesion biomaterial based on mussel adhesive protein fused with RGD peptide. Biomaterials 28:4039–4046CrossRefPubMedGoogle Scholar
  52. Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48:549–554CrossRefPubMedGoogle Scholar
  53. Jain P, Rahi P, Pandey V, Asati S, Soni V (2017) Nanostructure lipid carriers: a modish contrivance to overcome the ultraviolet effects. Egypt J Basic Appl Sci 4:89–100CrossRefGoogle Scholar
  54. Jao D, Mou X, Hu X (2016) Tissue regeneration: a silk road. J Funct Biomater 7:22CrossRefPubMedCentralGoogle Scholar
  55. Jiang J, Yang S, Wang J, Yang L, Xu Z, Yang T, Liu X, Zhang Q (2010) Sequential treatment of drug-resistant tumors with RGD-modified liposomes containing siRNA or doxorubicin. Eur J Pharm Biopharm 76:170–178CrossRefPubMedGoogle Scholar
  56. Jiang-Hua YA, Gui-Wang YA, Jie-Ping WA, Wu N, Zhuang GH (2007) Gene expression and activity analysis of a novel fusion protein (RGD) 3/Ttf. Chin J Biotechnol 23:409–413CrossRefGoogle Scholar
  57. Jo DH, Lee TG, Kim JH (2011) Nanotechnology and nanotoxicology in retinopathy. Int J Mol Sci 12:8288–8301CrossRefPubMedPubMedCentralGoogle Scholar
  58. Kang IC, Kim DS, Jang Y, Chung KH (2000) Suppressive mechanism of salmosin, a novel disintegrin in B16 melanoma cell metastasis. Biochem Biophys Res Comm 275:169–173CrossRefPubMedGoogle Scholar
  59. Katayama K, Furuki R, Yokoyama H, Kaneko M, Tachibana M, Yoshida I, Nagase H, Tanaka K, Sakurai F, Mizuguchi H (2011) Enhanced in vivo gene transfer into the placenta using RGD fiber-mutant adenovirus vector. Biomaterials 32:4185–4193CrossRefPubMedGoogle Scholar
  60. Kibria G, Hatakeyama H, Ohga N, Hida K, Harashima H (2011) Dual-ligand modification of PEGylated liposomes shows better cell selectivity and efficient gene delivery. J Control Release 153:141–148CrossRefPubMedGoogle Scholar
  61. Kim J, Nam HY, Kim TI, Kim PH, Ryu J, Yun CO, Kim SW (2011) Active targeting of RGD-conjugated bioreducible polymer for delivery of oncolytic adenovirus expressing shRNA against IL-8 mRNA. Biomaterials 32:5158–5166CrossRefPubMedPubMedCentralGoogle Scholar
  62. Kim TH, Jo YG, Jiang HH, Lim SM, Youn YS, Lee S, Chen X, Byun Y, Lee KC (2012) PEG-transferrin conjugated TRAIL (TNF-related apoptosis-inducing ligand) for therapeutic tumor targeting. J Control Release 162:422–428CrossRefPubMedPubMedCentralGoogle Scholar
  63. Koivunen E, Arap W, Valtanen H, Rainisalo A, Medina OP, Heikkilä P, Kantor C, Gahmberg CG, Salo T, Konttinen YT, Sorsa T (1999) Tumor targeting with a selective gelatinase inhibitor. Nat Biotechnol 17:768–774CrossRefPubMedGoogle Scholar
  64. Kong L, Wu Y, Alves CS, Shi X (2016) Efficient delivery of therapeutic siRNA into glioblastoma cells using multifunctional dendrimer-entrapped gold nanoparticles. Nanomedicine 12:3103–3115CrossRefGoogle Scholar
  65. Koo H, Huh MS, Sun IC, Yuk SH, Choi K, Kim K, Kwon IC (2011) In vivo targated delivery of nanoparticles for theranosis. Acc Chem Res 44:1018–1028CrossRefPubMedGoogle Scholar
  66. Körner M, Reubi JC (2007) NPY receptors in human cancer: a review of current knowledge. Peptides 28:419–425CrossRefPubMedGoogle Scholar
  67. Kulhari H, Pooja D, Shrivastava S, Telukutala SR, Barui AK, Patra CR, Vegi GM, Adams DJ, Sistla R (2015) Cyclic-RGDfK peptide conjugated succinoyl-TPGS nanomicelles for targeted delivery of docetaxel to integrin receptor over-expressing angiogenic tumours. Nanomed Nanotechnol Biol Med 11:1511–1520CrossRefGoogle Scholar
  68. Lai Y, Zhao P, Zhang Z, Li B, Wu J (2017) An effective peptide cargo carrier for the delivery of cisplatin in ovarian cancer cells. Dyes Pigm 143:342–347CrossRefGoogle Scholar
  69. Lamm MS, Sharma N, Rajagopal K, Beyer FL, Schneider JP, Pochan DJ (2008) Laterally spaced linear nanoparticle arrays templated by laminated -sheet fibrils. Adv Mater 20:447–451CrossRefGoogle Scholar
  70. Lee S, Xie J, Chen X (2010a) Peptide-based probes for targeted molecular imaging. Biochemistry 49:1364–1376CrossRefPubMedPubMedCentralGoogle Scholar
  71. Lee S, Xie J, Chen X (2010b) Peptides and peptide hormones for molecular imaging and disease diagnosis. Chem Soc Rev 110:3087–3111CrossRefGoogle Scholar
  72. Leng Q, Mixson AJ (2005) Modified branched peptides with a histidine-rich tail enhance in vitro gene transfection. Nucleic Acids Res 33:e40. CrossRefPubMedPubMedCentralGoogle Scholar
  73. Li ZJ, Cho CH (2010) Development of peptides as potential drugs for cancer therapy. Curr Pharm Des 16:1180–1189CrossRefPubMedGoogle Scholar
  74. Liu S (2006) Radiolabeled multimeric cyclic RGD peptides as integrin avß3 targeted radiotracers for tumor imaging. Mol Pharm 3:472–487CrossRefPubMedGoogle Scholar
  75. Liu G, Swierczewska M, Niu G, Zhang X, Chen X (2011a) Molecular imaging of cell-based cancer immunotherapy. Mol Biosyst 7:993–1003CrossRefPubMedPubMedCentralGoogle Scholar
  76. Liu TW, Chen J, Zheng G (2011b) Peptide-based molecular beacons for cancer imaging and therapy. Amino Acids 41:1123–1134CrossRefPubMedGoogle Scholar
  77. Liu B, Feng Y, Zhang JY, Li HM, Li XD, Jia HL, Li ZY, Feng J (2013) Imaging of bronchioloalveolar carcinoma in the mice with the αVβ3 integrin-targeted tracer 99 m Tc-RGD-4CK. Transl Res 162:174–180CrossRefPubMedGoogle Scholar
  78. Lopez-Rodriguez V, Gaspar-Carcamo RE, Pedraza-Lopez M, Rojas-Calderon EL, Arteaga de Murphy C, Ferro-Flores G, Avila-Rodriguez MA (2015) Preparation and preclinical evaluation of 66 Ga-DOTA-E(c(RGDfK)) as a potential theranostic radiopharmaceutical. Nucl Med Biol 42:109–114CrossRefPubMedGoogle Scholar
  79. Loyer P, Bedhouche W, Huang ZW, Cammas-Marion S (2013) Degradable and biocompatible nanoparticles decorated with cyclic RGD peptide for efficient drug delivery to hepatoma cells in vitro. Int J Pharm 454:727–737CrossRefPubMedGoogle Scholar
  80. Lu RM, Chang YL, Chen MS, Wu HC (2011) Single chain anti-c-Met antibody conjugated nanoparticles for in vivo tumor-targeted imaging and drug delivery. Biomaterials 32:3265–3274CrossRefPubMedGoogle Scholar
  81. Mancuso A, Sternberg CN (2005) Colorectal cancer and antiangiogenic therapy: what can be expected in clinical practice. Crit Rev Oncol Hematol 55:67–81CrossRefPubMedGoogle Scholar
  82. Meyer A, Auernheimer J, Modlinger A, Kessler H (2006) Targeting RGD recognizing integrins: drug development, biomaterial research, tumor imaging and targeting. Curr Pharm Des 12:2723–2747CrossRefPubMedGoogle Scholar
  83. Mitjans F, Meyer T, Fittschen C, Goodman S, Jonczyk A, Marshall JF, Reyes G, Piulats J (2000) In vivo therapy of malignant melanoma by means of antagonists of αv integrins. Int J Cancer 87:716–723CrossRefPubMedGoogle Scholar
  84. Mitra A, Mulholland J, Nan A, McNeill E, Ghandehari H, Line BR (2005) Targeting tumor angiogenic vasculature using polymer-RGD conjugates. J Control Rel 102:191–201CrossRefGoogle Scholar
  85. Moody TW, Nuche-Berenguer B, Jensen RT (2016) Vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide, and their receptors and cancer. Curr Opin Endocrinol Diabet Obes 23:38–47CrossRefGoogle Scholar
  86. Naik S, Patel D, Chuttani K, Mishra AK, Misra A (2012) In vitro mechanistic study of cell death and in vivo performance evaluation of RGD grafted PEGylated docetaxel liposomes in breast cancer. Nanomed Nanotechnol 8:951–962CrossRefGoogle Scholar
  87. Orsi S, Guarnieri D, de Capua A, Netti PA (2012) Gene-activated and cell-migration guiding PEG matrices based on three dimensional patterning of RGD peptides and DNA complexes. Acta Biomater 8:3228–3240CrossRefPubMedGoogle Scholar
  88. Pandey V, Gajbhiye KR, Soni V (2015) Lactoferrin-appended solid lipid nanoparticles of paclitaxel for effective management of bronchogenic carcinoma. Drug Deliv 22:199–205CrossRefPubMedGoogle Scholar
  89. Park J, Lee JJ, Jung JC, Yu DY, Oh C, Ha S, Kim TJ, Chang Y (2008) Gd-DOTA conjugate of RGD as a potential tumor-targeting MRI contrast agent. ChemBioChem 9:2811–2813CrossRefPubMedGoogle Scholar
  90. Patel O, Shulkes A, Baldwin GS (2006) Gastrin-releasing peptide and cancer. BBA Rev Cancer 1766:23–41Google Scholar
  91. Patra C, Ricciardi F, Engel FB (2012) The functional properties of nephronectin: an adhesion molecule for cardiac tissue engineering. Biomaterials 33:4327–4335CrossRefPubMedGoogle Scholar
  92. Pierschbacher MD, Ruoslahti E (1984) Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature 309:30–33CrossRefPubMedGoogle Scholar
  93. Plow EF, Haas TA, Zhang L, Loftus J, Smith JW (2000) Ligand binding to integrins. J Biol Chem 275:21785–21788CrossRefPubMedGoogle Scholar
  94. Pomper MG (2005) Translational molecular imaging for cancer. Cancer Imaging 5:S16–S26CrossRefGoogle Scholar
  95. Przystal JM, Umukoro E, Stoneham CA, Yata T, O’Neill K, Syed N, Hajitou A (2013) Proteasome inhibition in cancer is associated with enhanced tumor targeting by the adeno-associated virus/phage. Mol Oncol 7:55–66CrossRefPubMedGoogle Scholar
  96. Reynolds TJS, Schehr R, Liu D, Xu J, Miao Y, Hoffman TJ, Rold TL, Lewis MR, Smith CJ (2015) Characterization and evaluation of DOTA-conjugated Bombesin/RGD-antagonists for prostate cancer tumor imaging and therapy. Nucl Med Biol 42:99–108CrossRefGoogle Scholar
  97. Ritchie CK, Giordano A, Khalili K (2000) Integrin involvement in glioblastoma multiforme: possible regulation by NF-Κb. J Cell Physiol 184:214–221CrossRefPubMedGoogle Scholar
  98. Sakae M, Ito T, Yoshihara C, Iida-Tanaka N, Yanagie H, Eriguchi M, Koyama Y (2008) Highly efficient in vivo gene transfection by plasmid/PEI complexes coated by anionic PEG derivatives bearing carboxyl groups and RGD peptide. Biomed Pharmacother 62:448–453CrossRefPubMedGoogle Scholar
  99. Samanta S, Sistla R, Chaudhuri A (2010) The use of RGDGWK-lipopeptide to selectively deliver genes to mouse tumor vasculature and its complexation with p53 to inhibit tumor growth. Biomaterials 31:1787–1797CrossRefPubMedGoogle Scholar
  100. Schraa AJ, Kok RJ, Moorlag HE, Bos EJ, Proost JH, Meijer DK, de Leij LF, Molema G (2002) Targeting of RGD-modified proteins to tumor vasculature: a pharmacokinetic and cellular distribution study. Int J Cancer 102:469–475CrossRefPubMedGoogle Scholar
  101. Shachar M, Tsur-Gang O, Dvir T, Leor J, Cohen S (2011) The effect of immobilized RGD peptide in alginate scaffolds on cardiac tissue engineering. Acta Biomater 7:152–162CrossRefPubMedGoogle Scholar
  102. Shen JM, Gao FY, Yin T, Zhang HX, Ma M, Yang YJ, Yue F (2013) cRGD-functionalized polymeric magnetic nanoparticles as a dual-drug delivery system for safe targeted cancer therapy. Pharmacol Res 70:102–115CrossRefPubMedGoogle Scholar
  103. Singh RP, Sharma G, Kumari L, Koch B, Singh S, Bharti S. Rajinikanth PS, Pandey BL, Muthu MS (2016) RGD-TPGS decorated theranostic liposomes for brain targeted delivery. Colloids Surf B Biointerfaces 147:129–141CrossRefPubMedGoogle Scholar
  104. Stengel A, Taché YF (2017) Activation of brain somatostatin signaling suppresses CRF receptor-mediated stress response. Front Neurosci 11:231CrossRefPubMedPubMedCentralGoogle Scholar
  105. Sun X, Niu G, Yan Y, Yang M, Chen K, Ma Y, Chan N, Shen B, Chen X (2010) Phage display-derived peptides for osteosarcoma imaging. Clin Cancer Res 16:4268–4277CrossRefPubMedPubMedCentralGoogle Scholar
  106. Svensen N, Walton JG, Bradley M (2012) Peptides for cell selective drug delivery. Trends Pharmacol Sci 33:186–192CrossRefPubMedGoogle Scholar
  107. Swierczewska M, Lee S, Chen X (2011) Inorganic nanoparticles for multimodal molecular imaging. Mol Imaging 10(1):3–16CrossRefPubMedPubMedCentralGoogle Scholar
  108. Tai W, Mahato R, Cheng K (2010) The role of HER2 in cancer therapy and targeted drug delivery. J Control Release 146:264–275CrossRefPubMedPubMedCentralGoogle Scholar
  109. Tamerler C, Sarikaya M (2009) Genetically designed peptide-based molecular materials. ACS Nano 3:1606–1615CrossRefPubMedGoogle Scholar
  110. Tanabe N, Wheal BD, Kwon J, Chen HH, Shugg R, Sims SM, Goldberg HA, Dixon SJ (2011) Osteopontin signals through calcium and nuclear factor of activated T cells (NFAT) in osteoclasts: a novel RGD-dependent pathway promoting cell survival. J Biol Chem 286:39871–39881CrossRefPubMedPubMedCentralGoogle Scholar
  111. Temming K, Schiffelers RM, Molema G, Kok RJ (2005) RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature. Drug Resist Update 8:381–402CrossRefGoogle Scholar
  112. Thakare VS, Das M, Jain AK, Patil S, Jain S (2010) Carbon nanotubes in cancer theragnosis. Nanomedicine 5:1277–1301CrossRefPubMedGoogle Scholar
  113. Tocce E, Liliensiek S, Broderick A, Jiang Y, Murphy K, Murphy C, Lynn D, Nealey P (2013) The influence of biomimetic topographic features and the extracellular matrix peptide RGD on human corneal epithelial contact guidance. Acta Biomater 9:5040–5051CrossRefPubMedGoogle Scholar
  114. Trail PA, King DH, Dubowchik GM (2003) Monoclonal antibody drug immunoconjugates for targeted treatment of cancer. Cancer Immunol Immunother 52:328–337PubMedGoogle Scholar
  115. Tsiapa I, Loudos G, Varvarigou A, Fragogeorgi E, Psimadas D, Tsotakos T, Xanthopoulos S, Mihailidis D, Bouziotis P, Nikiforidis GC, Kagadis GC (2013) Biological evaluation of an ornithine-modified 99 m Tc-labeled RGD peptide as an angiogenesis imaging agent. Nucl Med Biol 40:262–272CrossRefPubMedGoogle Scholar
  116. Tugulu S, Silacci P, Stergiopulos N, Klok HA (2007) RGD—functionalized polymer brushes as substrates for the integrin specific adhesion of human umbilical vein endothelial cells. Biomaterials 28:2536–2546CrossRefPubMedGoogle Scholar
  117. Vachutinsky Y, Oba M, Miyata K, Hiki S, Kano MR, Nishiyama N, Koyama H, Miyazono K, Kataoka K (2011) Antiangiogenic gene therapy of experimental pancreatic tumor by sFlt-1 plasmid DNA carried by RGD-modified crosslinked polyplex micelles. J Control Release 149:51–57CrossRefPubMedGoogle Scholar
  118. Verrier S, Pallu S, Bareille R, Jonczyk A, Meyer J, Dard M, Amedee J (2002) Function of linear and cyclic RGD-containing peptides in osteoprogenitor cells adhesion process. Biomaterials 23:585–596CrossRefPubMedGoogle Scholar
  119. Wang ZH, Wang HM, Zheng WT, Zhang J, Zhao Q, Wang SF, Yang Z, Kong D (2011) Highly stable surface modifications of poly(3-caprolactone) (PCL) films by molecular self assembly to promote cells adhesion and proliferation. Chem Commun 47:8901–8903CrossRefGoogle Scholar
  120. Wang Z, Lee Y, Ho PC (2012) A novel dextran-oleate-cRGDfK conjugate for self-assembly of nanodrug. Nanomed Nanotechnol 8:194–203CrossRefGoogle Scholar
  121. Wang F, Li Y, Shen Y, Wang A, Wang S, Xie T (2013) The functions and applications of RGD in tumor therapy and tissue engineering. Int J Mol Sci 14:13447–13462CrossRefPubMedPubMedCentralGoogle Scholar
  122. Wang F, Chen L, Zhang R, Chen Z, Zhu L (2014) RGD peptide conjugated liposomal drug delivery system for enhance therapeutic efficacy in treating bone metastasis from prostate cancer. J Control Release 196:222–233CrossRefPubMedGoogle Scholar
  123. Weissleder R (2006) Molecular imaging in cancer. Science 312:1168–1171CrossRefPubMedGoogle Scholar
  124. Weissleder R, Schwaiger MC, Gambhir SS, Hricak H (2016) Imaging approaches to optimize molecular therapies. Sci Transl Med 8(355):355ps16CrossRefPubMedGoogle Scholar
  125. Wohlrab S, Müller S, Schmidt A, Neubauer S, Kessler H, Leal-Egaña A, Scheibel T (2012) Cell adhesion and proliferation on RGD-modified recombinant spider silk proteins. Biomaterials 33:6650–6659CrossRefPubMedGoogle Scholar
  126. Xu HM, Yin R, Chen L, Siraj S, Huang X, Wang M, Fang H, Wang Y (2008) An RGD-modified endostatin-derived synthetic peptide shows antitumor activity in vivo. Bioconj Chem 19:1980–1986CrossRefGoogle Scholar
  127. Xu Q, Liu Y, Su S, Li W, Chen C, Wu Y (2012a) Anti-tumor activity of paclitaxel through dual-targeting carrier of cyclic RGD and transferrin conjugated hyperbranched copolymer nanoparticles. Biomaterials 33:1627–1639CrossRefPubMedGoogle Scholar
  128. Xu W, Luo T, Li P, Zhou C, Cui D, Pang B, Ren Q, Fu S (2012b) RGD-conjugated gold nanorods induce radiosensitization in melanoma cancer cells by downregulating alpha(v)beta expression. Int J Nanomed 7:915–924Google Scholar
  129. Yamada KM, Geiger B (1997) Molecular interactions in cell adhesion complexes. Curr Opin Cell Biol 9:76–85CrossRefPubMedGoogle Scholar
  130. Yamaga LY, Cunha ML, Neto GC, Garcia MR, Yang JH, Camacho CP, Wagner J, Funari MB (2017) 68 Ga-DOTATATE PET/CT in recurrent medullary thyroid carcinoma:a lesion-by-lesion comparison with 111In-octreotide SPECT/CT and conventional imaging. Eur J Nucl Med Mol Imaging 44:1695–1701CrossRefPubMedGoogle Scholar
  131. Yang G, Sun H, Kong Y, Hou G, Han J (2014) Diversity of RGD radiotracers in monitoring antiangiogenesis of flavopiridol and paclitaxel in ovarian cancer xenograft-bearing mice. Nucl Med Biol 41:856–862CrossRefPubMedGoogle Scholar
  132. Yonenaga N, Kenjo E, Asai T, Tsuruta A. Shimizu K, Dewa T, Nango M, Oku N (2012) RGD-based active targeting of novel polycation liposomes bearing siRNA for cancer treatment. J Control Release 160:177–181CrossRefPubMedGoogle Scholar
  133. Yu YP, Wang Q, Liu YC, Xie Y (2014) Molecular basis for the targeted binding of RGD-containing peptide to integrin αVβ3. Biomaterials 35:1667–1675CrossRefPubMedGoogle Scholar
  134. Yue W, Sun Q, Landreneau R, Wu C, Siegfried JM, Yu J, Zhang L (2009) Fibulin-5 suppresses lung cancer invasion by inhibiting matrix metalloproteinase-7 expression. Cancer Res 69:6339–6346CrossRefPubMedPubMedCentralGoogle Scholar
  135. Zerda ADL, Liu Z, Bodapati S, Teed R, Vaithilingam S, Khuri-Yakub BT, Chen X, Dai H, Gambhir SS (2010) Ultrahigh sensitivity carbon nanotube agents for photoacoustic molecular imaging in living mice. Nano Lett 10:2168–2172CrossRefPubMedPubMedCentralGoogle Scholar
  136. Zhan C, Gu B, Xie C, Li J, Liu Y, Lu W (2010) Cyclic RGD conjugated poly(ethylene glycol)-co-poly(lactic acid) micelle enhances paclitaxel anti-glioblastoma effect. J Control Release 143:136–142CrossRefPubMedGoogle Scholar
  137. Zhan C, Meng Q, Li Q, Feng L, Zhu J, Lu W (2012) Cyclic RGD-polyethylene glycol-polyethylenimine for intracranial glioblastoma-targeted gene delivery. Chem Asian J 7:91–96CrossRefPubMedGoogle Scholar
  138. Zhang H, Lin CY, Hollister SJ (2009) The interaction between bone marrow stromal cells and RGD-modified three-dimensional porous polycaprolactone scaffolds. Biomaterials 30:4063–4069CrossRefPubMedPubMedCentralGoogle Scholar
  139. Zhang Y, Wang J, Bian D, Zhang X, Zhang Q (2010) Targeted delivery of RGD-modified liposomes encapsulating both combretastatin A-4 and doxorubicin for tumor therapy: in vitro and in vivo studies. Eur J Pharm Biopharm 74:467–473CrossRefPubMedGoogle Scholar
  140. Zhang L, Zhu S, Qian L, Pei Y, Qiu Y, Jiang Y (2011) RGD-modified PEG-PAMAM-DOX conjugates: in vitro and in vivo studies for glioma. Eur J Pharm Biopharm 79:232–240CrossRefPubMedGoogle Scholar
  141. Zhang H, Desai P, Koike Y, Carlin S, Tandon N, Touijer K, Weber W (2015) Dual-modality imaging of GRP receptor-expressing prostate cancer with new bombesin antagonist. J Nucl Med 56:1148–1148Google Scholar
  142. Zhao ZQ, Yang Y, Fang W, Liu S (2016) Comparison of biological properties of 99 m Tc-labeled cyclic RGD Peptide trimer and dimer useful as SPECT radiotracers for tumor imaging. Nucl Med Biol 43:661–669CrossRefPubMedPubMedCentralGoogle Scholar
  143. Zheng W, Wang Z, Song L, Zhao Q, Zhang J, Li D, Wang S, Han J, Zheng XL, Yang Z (2012) Endothelialization and patency of RGD-functionalized vascular grafts in a rabbit carotid artery model. Biomaterials 33:2880–2891CrossRefPubMedGoogle Scholar
  144. Zhu S, Qian L, Hong M, Zhang L, Pei Y, Jiang Y (2011) RGD-modified PEG-PAMAM-DOX conjugate: in vitro and in vivo targeting to both tumor neovascular endothelial cells and tumor cells. Adv Mater 23:H84–H89CrossRefPubMedGoogle Scholar
  145. Zilberberg L, Shinkaruk S, Lequin O, Rousseau B, Hagedorn M, Costa F, Caronzolo D, Balke M, Canron X, Convert O, Laïn G (2003) Structure and inhibitory effects on angiogenesis and tumor development of a new vascular endothelial growth inhibitor. J Biol Chem 278:35564–35573CrossRefPubMedGoogle Scholar
  146. Zitzmann S, Ehemann V, Schwab M (2002) Arginine-glycine-aspartic acid (RGD)-peptide binds to both tumor and tumor-endothelial cells in vivo. Cancer Res 62:5139–5143PubMedGoogle Scholar

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© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesDr. Hari Singh Gour UniversitySagarIndia

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