Ali Pourjavadi1, Zahra Mazaheri Tehrani2, Azardokht Abedin Moghanaki2. 1. Polymer Research Laboratory, Department of Chemistry, Sharif University of Technology, Azadi Avenue, P.O.Box 11365-9516, Tehran, Iran. purjavad@sharif.edu. 2. Polymer Research Laboratory, Department of Chemistry, Sharif University of Technology, Azadi Avenue, P.O.Box 11365-9516, Tehran, Iran.
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.
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 mesoporoussilica 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.
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