Journal of Sol-Gel Science and Technology

, Volume 81, Issue 2, pp 493–504 | Cite as

DOX delivery based on chitosan-capped graphene oxide-mesoporous silica nanohybride as pH-responsive nanocarriers

Original Paper: Nano-structured materials (particles, fibers, colloids, composites, etc.)


pH-responsive chitosan-coated graphene oxide-mesoporous silica nanoparticles (GMSN-Cs) was synthesized as a core–shell nanosheets to be used as DOX delivery system. First of all, an inorganic nanohybrid (GMSN) was prepared and subsequently, chitosan was attached to the mesoporous silica part through firm covalent bonds to form a reliable vector for DOX delivery. The chemico-physical properties of the nanosheets were specified, and DOX-loading efficiency and drug releasing was characterized in different pHs. At lower pH, the cumulative release of DOX-loaded GMSN-Cs was more than physiological pH. The in vitro hemolysis and in vivo biochemical analysis results demonstrate negligible toxicity of GMSN-Cs in mice at a high dosage of nanosheets and a disposal time (up to 10 days). DOX can be loaded efficiently on GMSN-Cs, and the resulting DOX–GMSN-Cs represents meaningful cytotoxicity in different pHs and concentrations for MCF-7 cells. The results and observations confirmed that the drug release of DOX-loaded GMSN-Cs can be controlled by physiological stimulant to reduce the side effects.

Graphical Abstract

Open image in new window


pH-responsive drug delivery system Chitosan Doxorubicin Graphene oxide Mesoporous silica Nanohybrid composites 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Rejinold NS, Thomas RG, Muthiah M, Lee HJ, Jeong YY, Park IK, Jayakumar R (2016) Breast tumor targetable Fe3O4 embedded thermo-responsive nanoparticles for radiofrequency assisted drug delivery. J Biomed Nanotechnol 12:43–55CrossRefGoogle Scholar
  2. 2.
    Xia, H, Zhao Y, Tong R (2016) Ultrasound-mediated polymeric micelle drug delivery. Adv Exp Med Biol 880:365–384Google Scholar
  3. 3.
    Wang D, Wu S (2016) Red-light-responsive supramolecular valves for photo-controlled drug release from mesoporous nanoparticles. Langmuir 32(2):632–6Google Scholar
  4. 4.
    Kanamala M, Wilson WR, Yang M, Palmer BD, Wu Z (2016) Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: a review. Biomaterials 85:152–167CrossRefGoogle Scholar
  5. 5.
    Nikouei NS, Ghasemi N, Lavasanifar A (2016) Temperature/pH responsive hydrogels based on poly (ethylene glycol) and functionalized poly (e-caprolactone) block copolymers for controlled delivery of macromolecules. Pharm Res 33:358–366CrossRefGoogle Scholar
  6. 6.
    Chen C, Zheng P, Cao Z, Ma Y, Li J, Qian H, Tao W, Yang X (2016) PEGylated hyperbranched polyphosphoester based nanocarriers for redox-responsive delivery of doxorubicin. Biomater Sci. doi:  10.1039/C5BM00440C
  7. 7.
    Tang J, Kong B, Wu H, Xu M, Wang Y, Wang Y, Zhao D, Zheng G (2013) Carbon nanodots featuring efficient FRET for real-time monitoring of drug delivery and two-photon imaging. Adv Mater 25:6569–6574CrossRefGoogle Scholar
  8. 8.
    Nasr FH, Khoee S (2015) Design, characterization and in vitro evaluation of novel shell crosslinked poly (butylene adipate)-co-N-succinyl chitosan nanogels containing loteprednol etabonate: a new system for therapeutic effect enhancement via controlled drug delivery. Eur J Med Chem 102:132–142CrossRefGoogle Scholar
  9. 9.
    Zhu M, Zhu Y, Zhang L, Shi J (2016) Preparation of chitosan/mesoporous silica nanoparticle composite hydrogels for sustained co-delivery of biomacromolecules and small chemical drugs. Sci Tech Adv Mater. doi:  10.1088/1468-6996/14/4/045005
  10. 10.
    Yang H, Bremner DH, Tao L, Li H, Hu J, Zhu L (2016) Carboxymethyl chitosan-mediated synthesis of hyaluronic acid-targeted graphene oxide for cancer drug delivery. Carbohyd Polym 135:72–78CrossRefGoogle Scholar
  11. 11.
    Wei Y, Zhou F, Zhang D, Chen Q, Xing D (2016) A graphene oxide based smart drug delivery system for tumor mitochondria-targeting photodynamic therapy. Nanoscale. doi:  10.1039/C5NR07785K
  12. 12.
    Liu J, Luo Z, Zhang J, Luo T, Zhou J, Zhao X, Cai K (2016) Hollow mesoporous silica nanoparticles facilitated drug delivery via cascade pH stimuli in tumor microenvironment for tumor therapy. Biomaterials 83:51–65CrossRefGoogle Scholar
  13. 13.
    He D, Li X, He X, Wang K, Tang J, Yang X, He X, Zou Z (2015) Noncovalent assembly of reduced graphene oxide and alkyl-grafted mesoporous silica: an effective drug carrier for near-infrared light-responsive controlled drug release. J Mater Chem B 3:5588–5594CrossRefGoogle Scholar
  14. 14.
    Meng Huan, Xue Min, Xia Tian, Zhao Yan-Li, Tamanoi Fuyuhiko, Stoddart JFraser, Jeffrey Zink, Andre Nel (2010) Autonomous in vitro anticancer drug release from mesoporous silica nanoparticles by pH-sensitive nanovalves. J Am Chem Soc 132:12690–12697CrossRefGoogle Scholar
  15. 15.
    Zhao Yan Li, Zongxi Li, Sanaz Kabehie, Youssry Botros, Stoddart JFraser, Jeffrey Zink (2010) pH-operated nanopistons on the surfaces of mesoporous silica nanoparticles. J Am Chem Soc 132:13016–13025CrossRefGoogle Scholar
  16. 16.
    Du Y, Guo S, Dong S, Wang E (2011) An integrated sensing system for detection of DNA using new parallel-motif DNA triplex system and graphene-mesoporous silica-gold nanoparticle hybrids. Biomaterials 32:8584–8592CrossRefGoogle Scholar
  17. 17.
    Wu H, Liu G, Zhuang Y, Wu D, Zhang H, Yang H, Hu H, Yang S (2011) The behavior after intravenous injection in mice of multiwalled carbon nanotube/Fe3O4 hybrid MRI contrast agents. Biomaterials 32:4867–4876CrossRefGoogle Scholar
  18. 18.
    Marcano DC, Kosynkin DV, Berlin JM, Sinitskii A, Sun Z, Slesarev A, Alemany LB, Lu W, Tour JM (2010) Improved synthesis of graphene oxide. ACS Nano 4:4806–4814CrossRefGoogle Scholar
  19. 19.
    Innocenzi P, Malfatti L, Carboni D (2015) Graphene and carbon nanodots in mesoporous materials: an interactive platform for functional applications. Nanoscale 7:12759–12772CrossRefGoogle Scholar
  20. 20.
    Manne S, Gaub HE (1995) Molecular organization of surfactants at solid-liquid interfaces. Science 270:1480CrossRefGoogle Scholar
  21. 21.
    Wan H, Zhang Y, Liu Z, Xu G, Huang G, Ji Y, Xiong Z, Zhang Q, Dong J, Zhang W (2014) Facile fabrication of a near-infrared responsive nanocarrier for spatiotemporally controlled chemo-photothermal synergistic cancer therapy. Nanoscale 6:8743–8753CrossRefGoogle Scholar
  22. 22.
    Pastor E, Matveeva E, Valle-Gallego A, Goycoolea FM, Garcia-Fuentes M (2011) Protein delivery based on uncoated and chitosan-coated mesoporous silicon microparticles. Colloids Surf B: Biointerfaces 88:601–609CrossRefGoogle Scholar
  23. 23.
    Ren Y, Abbood HA, He F, Peng H, Huang K (2013) Magnetic EDTA-modified chitosan/SiO2/Fe3O4 adsorbent: preparation, characterization, and application in heavy metal adsorption. Chem Eng J 226:300–311CrossRefGoogle Scholar
  24. 24.
    Tuinstra F, Koenig JL (1970) Raman spectrum of graphite. J Chem Phys 53:1126–1130CrossRefGoogle Scholar
  25. 25.
    Kudin KonstantinN, Ozbas Bulent, Schniepp Hannes, Robert Prud’Homme, Ilhan Aksay, Roberto Car (2008) Raman spectra of graphite oxide and functionalized graphene sheets. Nano Lett 8:36–41CrossRefGoogle Scholar
  26. 26.
    Shen Jianfeng, Hu Yizhe, Shi Min, Li Na, Hongwei Ma, Mingxin Ye (2010) One step synthesis of graphene oxide-magnetic nanoparticle composite. J Phys Chem C 114:1498–1503CrossRefGoogle Scholar
  27. 27.
    Hu X, Wang Y, Peng B (2014) Chitosan-capped mesoporous silica nanoparticles as pH-responsive nanocarriers for controlled drug release. Chem Asian J 9:319–327CrossRefGoogle Scholar
  28. 28.
    Long J, Xu E, Li X, Wu Z, Wang F, Xu X, Jin Z, Jiao A, Zhan X (2016) Effect of chitosan molecular weight on the formation of chitosan-pullulanase soluble complexes and their application in the immobilization of pullulanase onto Fe3O4-carrageenan nanoparticles. Food Chem 202:49–58CrossRefGoogle Scholar
  29. 29.
    Terada D, Kobayashi H, Zhang K, Tiwari A, Yoshikawa C, Hanagata N (2016) Transient charge-masking effect of applied voltage on electrospinning of pure chitosan nanofibers from aqueous solutions. Sci Tech Adv Mater. doi:  10.1088/1468-6996/13/1/015003
  30. 30.
    Bao H, Li L, Gan LH, Ping Y, Li J, Ravi P (2010) Thermo-and pH-responsive association behavior of dual hydrophilic graft chitosan terpolymer synthesized via ATRP and click chemistry. Macromolecules 43:5679–5687CrossRefGoogle Scholar
  31. 31.
    Wu H, Shi H, Wang Y, Jia X, Tang C, Zhang J, Yang S (2014) Hyaluronic acid conjugated graphene oxide for targeted drug delivery. Carbon 69:379–389CrossRefGoogle Scholar
  32. 32.
    Zhang D, Yu G, Long Z, Yang G, Wang B (2016) Controllable layer-by-layer assembly of PVA and phenylboronic acid-derivatized chitosan. Carbohyd Polym 140:228–232CrossRefGoogle Scholar
  33. 33.
    Unsoy G, Khodadust R, Yalcin S, Mutlu P, Gunduz U (2014) Synthesis of doxorubicin loaded magnetic chitosan nanoparticles for pH responsive targeted drug delivery. Eur J Pharm Sci 62:243–250CrossRefGoogle Scholar
  34. 34.
    Ali A, Suhail M, Mathew S, Shah MA, Harakeh SM, Ahmad S, Kazmi Z, Chaudhary A, Damanhouri GA (2016) Nanomaterial Induced Immune Responses and Cytotoxicity. J Nanosci Nanotechnol 16:40–57CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Polymer Laboratory, Chemistry Department, School of ScienceUniversity of TehranTehranIran

Personalised recommendations