SPION@APTES@FA-PEG@Usnic Acid Bionanodrug for Cancer Therapy

  • L. Alpsoy
  • A. Baykal
  • Md. Amir
  • Z. Ülker
  • M. Nawaz
Original Paper
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Accepted:
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Abstract

In this work, we aimed to develop stable usnic acid (UA)-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) as a potential drug carrier for in vitro analysis of MCF-7 (breast cancer cell line), HeLa (cervix cancer cell line), L929 (mouse fibroblast cell line), U87 (glioblastoma cell line, brain cancer), and A549 (human lung cancer cell line) cell lines. SPIONs were synthesized via the polyol method and functionalized with APTES using the Stöber method. Carboxylated polyethylene glycol (PEG-COOH), folic acid (FA), and carboxylated luteolin (CL) were conjugated on the surface via a carboxylic/amine group using the nanoprecipitation method, respectively. X-ray powder diffraction analysis confirmed the purity of the product with crystallite size of around 11 nm. Fourier-transformed infrared spectrophotometer (FT-IR) analyses explained the conjugation of all functional groups to the surface of SPIONs. The percentages of inorganic and organic content in the products were investigated via thermal gravimetric analyzer (TGA). For morphological analysis, a transmission electron microscope (TEM) was used. The superparamagnetic property of the product was also confirmed by vibrating sample magnetometer (VSM).

Keywords

Magnetic properties Nanodrug Drug release Cancer treatment Luteolin 
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References

  1. 1.
    Avendano, C., Menendez, J.C.: Medicinal Chemistry of Anticancer Drugs, 1st edn, p. 1 (Chapter 1). Elsevier, Amsterdam (2008)Google Scholar
  2. 2.
    Jemal, A., Bray, F., Center, M.M., Ferlay, J., Ward, E., Forman, D.: Global, cancer statistics. CA Cancer J. Clin. 61, 69–90 (2011)CrossRefGoogle Scholar
  3. 3.
    Wang, P., Cai, J., Chen, J.Q., Li, L.S., Sun, C.L., Xue, B., Ji, M.: 3D-QSAR and docking studies of piperidine carboxamide derivatives as ALK inhibitors. Med. Chem. Res. 23, 2576–2583 (2014)CrossRefGoogle Scholar
  4. 4.
    Gilchrest, B.A., Eller, M.S.: Cancer therapeutics: smart and smarter. Drugs Future 34, 205–216 (2009)CrossRefGoogle Scholar
  5. 5.
    Kamel, M.M., Abdo Megally, N.Y.: Synthesis of novel 1,2,4-triazoles, triazolothiadiazines and triazolothiadiazoles as potential anticancer agents. Eur. J. Med. Chem. 86, 75–80 (2014)CrossRefGoogle Scholar
  6. 6.
    La Regina, G., Bai, R., Coluccia, A., Famiglini, V., Pelliccia, S., Passacantilli, S., Rew, Y., Sun, D.: Discovery of a small molecule MDM2 inhibitor (AMG 232) for treating cancer. J. Med. Chem. 57, 6332–6341 (2014)CrossRefGoogle Scholar
  7. 7.
    Valente, S., Trisciuoglio, D., De Luca, T., Nebbioso, A., Labella, D., Lenoci, A., Bigogno, C., Dondio, G., Miceli, M., Brosch, G., Del Bufalo, D., Altucci, L., Mai, A.: 1,3,4-Oxadiazole-containing histone deacetylase inhibitors: anticancer activities in cancer cells. J. Med. Chem. 57, 6259–6265 (2014)CrossRefGoogle Scholar
  8. 8.
    Varbanov, H.P., Goschl, S., Heffeter, P., Theiner, S., Roller, A., Jensen, F., Jakupec, M.A., Berger, W., Galanski, M., Keppler, B.K.: A novel class of bis- and tris-chelate diam (m) inebis(dicarboxylato) platinum(IV) complexes as potential anticancer prodrugs. J. Med. Chem. 57, 6751–6764 (2014)CrossRefGoogle Scholar
  9. 9.
    Wang, M.J., Liu, Y.Q., Chang, L.C., Wang, C.Y., Zhao, Y.L., Zhao, X.B., Qian, K., Nan, X., Yang, L., Yang, X.M, Hung, H.Y., Yang, J.S., Kuo, D.H., Goto, M., Morris-Natschke, S.L., Pan, S.L., Teng, C.M., Kuo, S.C., Wu, T.S., Wu, Y.C., Lee, K.H.: Design, synthesis, mechanisms of action, and toxicity of novel 20(s)-sulfonylamidine derivatives of camptothecin as potent antitumor agents. J. Med. Chem. 57, 6008–6018 (2014)CrossRefGoogle Scholar
  10. 10.
    Wang, C., Ravi, S., Garapati, U.S., Das, M., Howell, M., Mallela, J., Alwarappan, S., Mohapatra, S.S., Mohapatra, S.: Multifunctional chitosan magnetic-graphene(CMG) nanoparticles: a theranostic platform for tumor-targeted co-delivery of drugs, genes and MRI contrast agents. J. Mater. Chem. B 1, 4396–4405 (2013)CrossRefGoogle Scholar
  11. 11.
    Mandal, A., Sekar, S., Kanagavel, M., Chandrasekaran, N., Mukherjee, A., Sastry, T.P.: Collagen based magnetic nanobiocomposite as MRI contrast agent andfor targeted delivery in cancer therapy, Biochim. Biophys. Acta (BBA)-Gen. Subj. 1830, 4628–4633 (2013)CrossRefGoogle Scholar
  12. 12.
    Majewski, A.P., Schallon, A., Jérôme, V., Freitag, R., Müller, A.H.E., Schmalz, H.: Dual-responsive magnetic core–shell nanoparticles for nonviral gene deliveryand cell separation. Biomacromolecules 13, 857–866 (2012)CrossRefGoogle Scholar
  13. 13.
    Liu, H., Li, S., Liu, L., Tian, L., He, N.: An integrated and sensitive detectionplatform for biosensing application based on Fe@Au magnetic nanoparticlesas bead array carries. Biosens. Bioelectron. 26, 1442–1448 (2010)CrossRefGoogle Scholar
  14. 14.
    Chandra, S., Barola, N., Bahadur, D.: Impedimetric biosensor for early detectionof cervical cancer. Chem. Commun. 47, 11258–11260 (2011)CrossRefGoogle Scholar
  15. 15.
    Yalcı̧n, S., Erkan, M., Ünsoy, G., Parsian, M., Kleeff, J., Gündüz, U.: Effect of gemcitabine and retinoic acid loaded PAMAM dendrimer-coated magneticnanoparticles on pancreatic cancer and stellate cell lines. Biomed. Pharmacother. 68, 737–743 (2014)CrossRefGoogle Scholar
  16. 16.
    Majewski, A.P., Schallon, A., Jérôme, V., Freitag, R., Müller, A.H.E., Schmalz, H.: Dual-responsive magnetic core–shell nanoparticles for nonviral gene delivery and cell separation. Biomacromolecules 13, 857–866 (2012)CrossRefGoogle Scholar
  17. 17.
    Shan, Z., Jiang, Y., Guo, M., Bennett, J.C., Li, X., Tian, H., Oakes, K., Zhang, X., Zhou, Y., Huang, Q., Chen, H., Promoting, D N A: loading on magnetic nanoparticles using aDNA condensation strategy. Colloids Surf. B: Biointerfaces 125, 247–254 (2015)CrossRefGoogle Scholar
  18. 18.
    Zhang, L., Dong, W.-F., Sun, H.-B.: Multifunctional superparamagnetic ironoxide nanoparticles: design, synthesis and biomedical photonic applications. Nanoscale 5, 7664–7684 (2013)ADSCrossRefGoogle Scholar
  19. 19.
    Roy, E., Patra, S., Madhuri, R., Sharma, P.K.: Stimuli-responsive poly(N-isopropylacrylamide)-co-tyrosine@gadolinium: iron oxide nanoparticle-basednanotheranostic for cancer diagnosis and treatment. Colloids Surf. B: Biointerfaces 142, 248–258 (2016)CrossRefGoogle Scholar
  20. 20.
    Mahmoudi, M., Sant, S., Wang, B., Laurent, S., Sen, T.: Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy. Adv. Drug Deliv. Rev. 63, 24–46 (2011)CrossRefGoogle Scholar
  21. 21.
    Ling, D., Hackett, M.J., Hyeon, T.: Surface ligands in synthesis modification,assembly and biomedical applications of nanoparticles. Nano Today 9, 457–477 (2014)CrossRefGoogle Scholar
  22. 22.
    Liu, X.L., Choo, E.S.G., Ahmed, A.S., Zhao, L.Y., Yang, Y., Ramanujan, R.V., Xue, J.M., Fan, D.D., Fan, H.M., Ding, J.: Magnetic nanoparticle-loaded polymernanospheres as magnetic hyperthermia agents. J. Mater. Chem. B 2, 120–128 (2014)CrossRefGoogle Scholar
  23. 23.
    Sun, L., Wu, Q., Peng, F., Liu, L., Gong, C.: Strategies of polymeric nanoparticles forenhanced internalization in cancer therapy. Colloids Surf. B: Biointerfaces 135, 56–72 (2015)CrossRefGoogle Scholar
  24. 24.
    Lu, X., Jiang, R., Yang, M., Fan, Q., Hu, W., Zhang, L., Yang, Z., Deng, W., Shen, Q., Huang, Y., Liu, X., Huang, W.: Monodispersed grafted conjugated polyelectrolyte-stabilized magnetic nanoparticles as multifunctional platform for cellular imaging and drug delivery. J. Mater. Chem. B 2, 376–386 (2014)CrossRefGoogle Scholar
  25. 25.
    Rouhollah, K., Pelin, M., Serap, Y., Gozde, U., Ufuk, G.: Doxorubicin loading, release, and stability of polyamidoamine dendrimer-coated magnetic nanoparticles. J. Pharm. Sci. 102, 1825–1835 (2013)CrossRefGoogle Scholar
  26. 26.
    Cocchietto, M., Skert, N., Nimis, P.L., Sava, G.: Naturwissenschaften 89(4), 137–146 (2002)ADSCrossRefGoogle Scholar
  27. 27.
    Grumezescu, A.M., Saviuc, C., Chifiriuc, M.C., Hristu, R., Mihaiescu, D.E., Balaure, P., Stanciu, G., Lazar, V.: IEEE Trans. Nanobiosci. 10(4), 269–274 (2011)CrossRefGoogle Scholar
  28. 28.
    Chifiriuc, M.C., Ditu̧, L.M., Oprea, E., Litȩscu, S., Bucur, M., Marut escu, L., Enache, G., Saviuc, C., Burlibasa̧, M., Traistaru, T., Tanase, G., Lazar, V.: Roum Arch. Microbiol. Immunol. 68(4), 215–222 (2009)Google Scholar
  29. 29.
    Mitrovic, T., Stamenkovic, S., Cvetkovic, V., Tosic, S., Stankovic, M., Radojevic, I., Stefanovic, O., Comic, L., Dacic, D., Curcic, M., Markovic, S.: Int. J. Mol. Sci. 12(8), 5428–5448 (2011)CrossRefGoogle Scholar
  30. 30.
    Cocchietto, M., Skert, N., Nimis, P., Sava, G.: A review on usnic acid: an interesting natural compound. Naturwissenschaften 89, 137–146 (2002)ADSCrossRefGoogle Scholar
  31. 31.
    Francolini, I., Taresco, V., Crisante, F., Martinelli, A., D’Ilario, L., Piozzi, A.: Water soluble usnic acid-polyacrylamide complexes with enhanced antimicrobial activity against Staphylococcus epidermidis. Int. J. Mol. Sci 14, 7356–7369 (2013)CrossRefGoogle Scholar
  32. 32.
    da Silva Santos, N.P., Nascimento, S.C., Wanderley, M.S., Pontes-Filho, N.T., da Silva, J.F., de Castro, C.M., Pereira, E.C., da Silva, N.H., Honda, N.K., Santos-Magalhaes, N.S.: Nanoencapsulation of usnic acid: an attempt to improve antitumour activity and reduce hepatotoxicity. Eur. J. Pharm. Biopharm. 64, 154–160 (2006)CrossRefGoogle Scholar
  33. 33.
    Lira, M.C., Siqueira-Moura, M.P., Rolim-Santos, H.M., Galetti, F.C., Simioni, A.R., Santos, N.P., Tabosa Do Egito, E.S., Silva, C.L., Tedesco, A.C., Santos-Magalhaes, N.S.: In vitro uptake and antimycobacterial activity of liposomal usnic acid formulation. J. Liposome Res. 19, 49–58 (2009)CrossRefGoogle Scholar
  34. 34.
    Martinelli, A., Bakry, A., D’Ilario, L., Francolini, I., Piozzi, A., Taresco, V.: Release behavior and antibiofilm activity of usnic acid-loaded carboxylated poly(l-lactide) microparticles. Eur. J. Pharm. Biopharm. 88, 415–423 (2014)CrossRefGoogle Scholar
  35. 35.
    Grumezescu, A.M., Saviuc, C., Chifiriuc, M.C., Hristu, R., Mihaiescu, D.E., Balaure, P., Stanciu, G., Lazar, V.: Inhibitory activity of Fe3 O 4/oleic acid/usnic acid-core/shell/extrashell nanofluid on S. aureus biofilm development. IEEE Trans. Nanobiosci. 10, 269–274 (2011)CrossRefGoogle Scholar
  36. 36.
    Grumezescu, A.M., Cotar, A.I., Andronescu, E., Ficai, A., Ghitulica, C.D., Grumezescu, V., Vasile, B.S., Chifiriuc, M.C.: In vitro activity of the new water-dispersible Fe3 O 4@ usnic acid nanostructure against planktonic and sessile bacterial cells. J. Nanopart. Res. 15, 1766–1776 (2013)ADSCrossRefGoogle Scholar
  37. 37.
    Baykal, A., Amir, Md., Güner, S., Sözeri, H.: Preparation and characterization of SPION functionalized via caffeic acid. J. Magn. Magn. Mater. 395, 199–204 (2015)ADSCrossRefGoogle Scholar
  38. 38.
    Manikandan, A., Vijaya, J.J., Mary, J. Arul., Kennedy, L.J., Dinesh, A.: Structural, optical and magnetic properties of Fe3 O 4 nanoparticles prepared by a facile microwave combustion method. J. Ind. Eng. Chem. 20, 2077–2085 (2014)CrossRefGoogle Scholar
  39. 39.
    Akal, Z.U., Alpsoy, L., Baykal, A.: Superparamagnetic iron oxide conjugated with folic acid and carboxylated quercetin for chemotherapy applications. Ceram. Int. 42, 9065–9072 (2016)CrossRefGoogle Scholar
  40. 40.
    Marıawıllıam, S.M., Francıs, A.P., Devasena, T.: In situ isolation and characterizatıon of nano-usnic acid for medical applications. Int. J. Pharm. Pharm. Sci. 6(6), 222–226 (2014)Google Scholar
  41. 41.
    Zhang, Y., Zhang, J.: Surface modification of monodisperse magnetite nanoparticles for improved intracellular uptake to breast cancer cells. J. Colloid Interface Sci. 283, 352–357 (2005)ADSCrossRefGoogle Scholar
  42. 42.
    Dousseau, F., Pezolet, M.: Determination of the secondary structure content of proteins in aqueous solutions from their amide I and amide II infrared bands. Comparison between classical and partial least-squares methods. Biochemistry 29, 8771–8779 (1990)CrossRefGoogle Scholar
  43. 43.
    Barth, A., Zscherp, C.: What vibrations tell about proteins. Q. Rev. Biophys. 35, 369–430 (2002)CrossRefGoogle Scholar
  44. 44.
    Kurtan, U., Onuş, E., Amir, Md., Baykal, A.: Fe3 O 4@Hpipe-4@Cu Nanocatalyst for hydrogenation of nitro-aromatics and azo dyes. J. Inorg. Organomet. Polym. 25, 1120–1128 (2015)CrossRefGoogle Scholar
  45. 45.
    Manikandan, A., Vijaya, J.J., Joh, J.K.: Structural, optical and magnetic properties of porous α-Fe2 O 3 nanostructures prepared by rapid combustion method. J. Nanosci. Nanotechnol. 13, 2986–2992 (2013)CrossRefGoogle Scholar
  46. 46.
    Zhang, L., Wu, Z., Chen, L., Zhang, L., Li, X., Xu, H., Wang, H., Zhu, G.: Preparation of magnetic Fe3 O 4/TiO2/Ag composite microspheres with enhanced photocatalytic activity. Solid State Sci. 52, 42–48 (2016)ADSCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • L. Alpsoy
    • 1
  • A. Baykal
    • 2
  • Md. Amir
    • 3
  • Z. Ülker
    • 1
  • M. Nawaz
    • 2
  1. 1.Gama Mechatronics CompanyNilüferTurkey
  2. 2.Department of Nano-Medicine Research, Institute for Research and Medical Consultations (IRMC)University of DammamDammamSaudi Arabia
  3. 3.Faculty of Engineering, Department of ChemistryIstanbul UniversityAvcilarTurkey

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