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

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

KEY WORDS

folic acid gemcitabine graphene oxide mesoporous silica pH-responsive 

Abbreviations

AFM

Atomic force microscope

APTS

Aminopropyltriethoxysilane

BET

Brunauer–Emmett–Teller

CTAB

Cetyltrimethyl ammonium bromide

DCC

Dicylohexylcarbodiimide

DLS

Dynamic light scattering

DMSO

Dimethylsulfoxide

EDA

Ethylenediamine

FA

Folic acid

FBS

Fetal bovine serum

Fe3O4@GO@mSiO2

Magnetic mesoporous silica coated graphene oxide

FT-IR

Fourier transform infrared

GO

Graphene oxide

MTT

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

PAMAM

Polyamidoamine

PBS

Phosphate buffer saline

PEG

Polyethylene glycol

TEM

Transmission electron microscope

TEOS

Tetraethyl orthosilicate

TGA

Thermogravimetric analysis

WAXD

Wide angle X-ray diffraction

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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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