Pharmaceutical Research

, Volume 33, Issue 2, pp 417–432 | Cite as

Folate-Conjugated pH-Responsive Nanocarrier Designed for Active Tumor Targeting and Controlled Release of Gemcitabine

  • Ali Pourjavadi
  • Zahra Mazaheri Tehrani
  • Azardokht Abedin Moghanaki
Research Paper



The prime end of this study was to design a novel pH-sensitive as well as a PEGylated dendritic nanocarrier for both controllable and traceable gemcitabine delivery to cancerous cells. To accomplish this goal, we took advantage of a hybrid of nanoparticles including: mesoporous silica, graphene oxide and magnetite.


The nanocarrier was prepared in a multi-step synthesis route. First, magnetite mesoporous silica was deposited on the graphene oxide matrix. Then, polyamidoamine dendrimers (up to generation 1.5) with pentaethylene hexamine end groups were grafted on the surface of the nanoparticles. In order to enhance the biostability, and as the next step, the nanocarrier was modified by polyethylene glycol. Finally, these particles were functionalized by folic acid as tumor targeting agents.


According to the dynamic light scattering results, the hydrodynamic diameter of magnetic mesoporous silica graphene oxide hybrid nanoparticle was 152 ± 3 nm, while for the supramolecular hybrid nanoparticles it was about 324 ± 12 nm. Attained through the adsorption branch, the average pore diameter of these nanoparticles was 7.6 nm. Zeta potential test indicated −27.1 mV value for hybrid nanoparticles and +7.35 mV for supramolecular hybrid nanoparticles. Besides, cytotoxicity assay showed enhanced cytotoxicity of epidermoid carcinoma cell line A431 in the presence of folate conjugated carriers. The maximum release occurred at the pH 5.5, because the dendritic structure was in the open state rather than compact state.


The enhanced cytotoxicity of the epidermoid carcinoma cell line A431 in the presence of folate conjugated carriers, confirmed the improved cancerous cells uptake. Also, the positive surface potential would be a good property for the biological applications because the inherent negative-charged surface of cell membranes facilitates the uptake of positive particles by electrostatic interactions.


folic acid gemcitabine graphene oxide mesoporous silica pH-responsive 



Atomic force microscope






Cetyltrimethyl ammonium bromide




Dynamic light scattering






Folic acid


Fetal bovine serum


Magnetic mesoporous silica coated graphene oxide


Fourier transform infrared


Graphene oxide


3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide




Phosphate buffer saline


Polyethylene glycol


Transmission electron microscope


Tetraethyl orthosilicate


Thermogravimetric analysis


Wide angle X-ray diffraction



We are grateful to Miss. Mohadeseh Doroudian and Mr. Behzad Pourbadiei for the help in MTT assay.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Ali Pourjavadi
    • 1
  • Zahra Mazaheri Tehrani
    • 1
  • Azardokht Abedin Moghanaki
    • 1
  1. 1.Polymer Research Laboratory, Department of ChemistrySharif University of TechnologyTehranIran

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