Immobilized Peptide on the Surface of Poly l-DOPA/Silica for Targeted Delivery of 5-Fluorouracil to Breast Tumor

  • Maryam Nazemian
  • Vida HojatiEmail author
  • Saeed Zavareh
  • Hamid Madanchi
  • Hamid Hashemi-MoghaddamEmail author


Chemotherapy using drug delivery systems can target tumor cells selectively and do not affect normal cells. In this paper, a specific drug delivery system with immobilized NL2 peptide on the surface of polymeric nano drug was designed for treatment of breast tumor. The tertiary structure of NL2 peptide (AEGEFIHNRYNRFFYWYGDPAK) was selected from the database and synthesized. After that, it was coupled to the synthesized poly 3,4-dihydroxy-l-phenylalanine (DOPA)/SiO2 nano-composite and examined for targeted 5-fluorouracil (5-FU) delivery in nude mice bearing MCF7 human breast carcinoma cells. Investigation of drug deposition in different tissue and in vivo experiments showed drug in combination with functionalized nano-composite with peptide (DPP) improve targeting properties of drug and 5-FU concentration was significantly increased in tumor rather than other tissues. In addition, this functionalization increases antitumor and targeting efficacy than the free 5-FU and non-functionalized nanocomposite.The poly DOPA functionalized peptide is a powerful agent for targeted delivery of anticancer drugs such as 5FU to tumor cells.


5-Fluorouracil Poly 3,4-dihydroxy-l-phenylalanine Anti-cancer peptide Breast cancer 



The authors are grateful for the MCF7 cell line given by the Pasteur Institute of Iran.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All experiments were performed according to the The International Guiding Principles for Biomedical Research Involving Animals and were approved by the Institutional Bioethics Commission. This investigation does not contain any studies with human participants performed by any of the authors.


  1. Adams GP, Weiner LM (2005) Monoclonal antibody therapy of cancer. Nat Biotechnol 23:1147CrossRefGoogle Scholar
  2. Aina OH, Sroka TC, Chen ML, Lam KS (2002) Therapeutic cancer targeting peptides. Peptide Science: Original Research on Biomolecules 66:184–199CrossRefGoogle Scholar
  3. Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279:377–380CrossRefGoogle Scholar
  4. Brahmbhatt H, MacDiarmid J, Engeneic Molecular Deliver Pty Ltd (2018) Targeted delivery of drugs, therapeutic nucleic acids and functional nucleic acids to mammalian cells via intact killed bacterial cells. US Patent Application 15/881,801Google Scholar
  5. Chilkoti A, Chen G, Stayton PS, Hoffman AS (1994) Site-specific conjugation of a temperature-sensitive polymer to a genetically engineered protein. Bioconjugate Chem 5:504–507CrossRefGoogle Scholar
  6. Cho H-S, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW Jr, Leahy DJ (2003) Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421:756CrossRefGoogle Scholar
  7. Das P, Jana NR (2015) Dopamine functionalized polymeric nanoparticle for targeted drug delivery. RSC Adv 5:33586–33594CrossRefGoogle Scholar
  8. Del Nozal M, Bernal J, Marenero P, Pampliega A (1994) Extraction Procedures for the HPLC determination of 5-fluorouracil in biological samples. J Liq Chromatogr Relat Technol 17:1621–1636CrossRefGoogle Scholar
  9. Ellerby HM, Arap W, Ellerby LM, Kain R, Andrusiak R, Del Rio G, Krajewski S, Lombardo CR, Rao R, Ruoslahti E (1999) Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med 5:1032CrossRefGoogle Scholar
  10. Gao H, Xiong Y, Zhang S, Yang Z, Cao S, Jiang X (2014) RGD and interleukin-13 peptide functionalized nanoparticles for enhanced glioblastoma cells and neovasculature dual targeting delivery and elevated tumor penetration. Mol Pharm 11:1042–1052CrossRefGoogle Scholar
  11. Gong C, Lu C, Li B, Shan M, Wu G (2017) Injectable dopamine-modified poly (α, β-aspartic acid) nanocomposite hydrogel as bioadhesive drug delivery system. J Biomed Mater Res Part A 105:1000–1008CrossRefGoogle Scholar
  12. Hashemi-Moghaddam H, Zavareh S, Gazi EM, Jamili M (2018) Assessment of novel core–shell Fe3O4@ poly l–DOPA nanoparticles for targeted Taxol® delivery to breast tumor in a mouse model. Mater Sci Eng C 93:1036–1043CrossRefGoogle Scholar
  13. Horning SJ, Younes A, Jain V, Kroll S, Lucas J, Podoloff D, Goris M (2005) Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol 23:712–719CrossRefGoogle Scholar
  14. Iturralde D, Spaide R, Meyerle C, Yannuzzi L, Fisher Y, Sorenson J, Slakter J, Klancnik J (2006) Intravitreal bevacizumab (Avastin) treatment of macular edema in central retinal vein occlusion. Invest Ophthalmol Vis Sci 47:4273–4273Google Scholar
  15. Jiang K, Schadler LS, Siegel RW, Zhang X, Zhang H, Terrones M (2004) Protein immobilization on carbon nanotubes via a two-step process of diimide-activated amidation. J Mater Chem 14:37–39CrossRefGoogle Scholar
  16. Keservani RK, Sharma AK, Jarouliya U (2015) Protein and peptide in drug targeting and its therapeutic approach. Ars Pharm 56(3):165–177CrossRefGoogle Scholar
  17. Martín M, Salazar P, Villalonga R, Campuzano S, Pingarrón JM, González-Mora JL (2014) Preparation of core–shell Fe3O4@ poly (dopamine) magnetic nanoparticles for biosensor construction. J Mater Chem B 2:739–746CrossRefGoogle Scholar
  18. Masoudipour E, Kashanian S, Maleki N (2017) A targeted drug delivery system based on dopamine functionalized nano graphene oxide. Chem Phys Lett 668:56–63CrossRefGoogle Scholar
  19. Oh S, Kim BJ, Singh NP, Lai H, Sasaki T (2009) Synthesis and anti-cancer activity of covalent conjugates of artemisinin and a transferrin-receptor targeting peptide. Cancer Lett 274:33–39CrossRefGoogle Scholar
  20. Park CB, Kim HS, Kim SC (1998) Mechanism of action of the antimicrobial peptide buforin II: buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions. Biochem Biophys Res Commun 244:253–257CrossRefGoogle Scholar
  21. Perk LR, Visser OJ, Stigter-van Walsum M, Vosjan MJ, Visser GW, Zijlstra JM, Huijgens PC, van Dongen GA (2006) Preparation and evaluation of 89 Zr-Zevalin for monitoring of 90 Y-Zevalin biodistribution with positron emission tomography. Eur J Nucl Med Mol Imaging 33:1337–1345CrossRefGoogle Scholar
  22. Sadatmousavi P, Soltani M, Nazarian R, Jafari M, Chen P (2011) Self-assembling peptides: potential role in tumor targeting. Curr Pharm Biotechnol 12:1089–1100CrossRefGoogle Scholar
  23. Saeed AF, Wang R, Ling S, Wang S (2017) Antibody engineering for pursuing a healthier future. Front Microbiol 8:495Google Scholar
  24. Stewart JM, Soricimed Biopharma Inc (2018) Compounds and methods for the detection of TRPV-6 cancers and drug delivery. US Patent Application 10/064,964Google Scholar
  25. Tian T, Zhang H-X, He C-P, Fan S, Zhu Y-L, Qi C, Huang N-P, Xiao Z-D, Lu Z-H, Tannous BA (2018) Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy. Biomaterials 150:137–149CrossRefGoogle Scholar
  26. Tran TN, Pham TVA, Le MLP, Nguyen TPT (2013) Synthesis of amorphous silica and sulfonic acid functionalized silica used as reinforced phase for polymer electrolyte membrane. Adv Nat Sci 4:045007Google Scholar
  27. Urbanelli L, Ronchini C, Fontana L, Menard S, Orlandi R, Monaci P (2001) Targeted gene transduction of mammalian cells expressing the HER2/neu receptor by filamentous phage1. J Mol Biol 313:965–976CrossRefGoogle Scholar
  28. Vaezi M, Sadrnezhaad S, Nikzad L (2008) Electrodeposition of Ni–SiC nano-composite coatings and evaluation of wear and corrosion resistance and electroplating characteristics. Colloids Surf A 315:176–182CrossRefGoogle Scholar
  29. Wang D-s, Li J-g, Li H-p, Tang F-q (2009) Preparation and drug releasing property of magnetic chitosan-5-fluorouracil nano-particles. Trans Nonferrous Met Soc China 19:1232–1236CrossRefGoogle Scholar
  30. Wu XL, Kim JH, Koo H, Bae SM, Shin H, Kim MS, Lee B-H, Park R-W, Kim I-S, Choi K (2010) Tumor-targeting peptide conjugated pH-responsive micelles as a potential drug carrier for cancer therapy. Bioconjugate Chem 21:208–213CrossRefGoogle Scholar
  31. Zavareh S, Mahdi M, Erfanian S, Hashemi-Moghaddam H (2016) Synthesis of polydopamine as a new and biocompatible coating of magnetic nanoparticles for delivery of doxorubicin in mouse breast adenocarcinoma. Cancer Chemother Pharmacol 78:1073–1084CrossRefGoogle Scholar
  32. Zhang Y, Baekgaard-Laursen M, Mouritzen SA, Lynge ME, Schattling PS, Danial M, Postma A, Städler B (2016) Tannic acid and cholesterol–dopamine as building blocks in composite coatings for substrate-mediated drug delivery. Polym Int 65:1306–1314CrossRefGoogle Scholar
  33. Zhang P-B, Tang A-Q, Wang Z-H, Lu J-Y, Zhu B-K, Zhu L-P (2018) Tough poly (L-DOPA)-containing Double Network Hydrogel Beads with High Capacity of Dye Adsorption. Chin J Polym Sci 36:1251–1261CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Biology, Damghan BranchIslamic Azad UniversityDamghanIran
  2. 2.School of BiologyDamghan UniversityDamghanIran
  3. 3.Drug Design and Bioinformatics Unit, Department of Medical Biotechnology, Biotechnology Research CenterPasteur Institute of IranTehranIran
  4. 4.Department and Center for Biotechnology ResearchSemnan University of Medical SciencesSemnanIran
  5. 5.Department of Chemistry, Damghan BranchIslamic Azad UniversityDamghanIran

Personalised recommendations