In-Vitro Study on Organic-Inorganic Hybrid Composite of Graphene Oxide-Fe3O4/ Doxorubicin/TiO2 as a Targeted Drug-Delivery System

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In our present work, we report a novel targeted drug-delivery system by using a simple and cost-effective procedure. Firstly, magnetic graphene oxide (GO-Fe3 O4 ) was prepared by chemical co-precipitation of Fe3 O4 magnetic nanoparticles on GO platelets and it was used as carrier for loading of doxorubicin (DOX), an anticancer drug. After loading DOX, in order to prevent the premature degradation of drug from GO-Fe3 O4 /DOX composite, it was coated with TiO2 , an inorganic porous coating, by using titanium (IV) butoxide, as precursor. In this way the GO-Fe3 O4 /DOX/TiO2 hybrid composite was synthesized. Then, the drug release of composites were monitored using UV-Vis absorbance technique and the results revealed that incorporation of porous TiO2 coating, enhanced the drug entrapment and decreased the amount of drug release, in which at pH 7.4, 56% and 15% of DOX was released from uncoated and coated composites, respectively. Moreover, after studying the release rate at pH 5.4, corresponds to the endosomal pH of cancer cell, the results showed that drug release is pH-sensitive, because the release rate of DOX in the pH 5.4 noticeably enhanced, compared to pH 7.4. Also, the MTT assays of hybrid composite confirmed its superior responsive to cancer cell lines.

Nowadays cancer is one of the main cause of death in around the world so that, in each year it is responsible for more 13% of death incidence. The World Health Organization in 2015 estimated that 84 million people were died by cancer in the last decade. In addition, GLOBOCAN 2012 reported 14.1 million new cancer per year in the world and estimated that by 2025 this number will raise up to 19.3 million. Currently, four conventional therapeutic strategies for cancer therapy are surgery, radiation, chemotherapy and immunotherapy. Among these, chemotherapy is more common used but it has many disadvantages like high toxicity and side effects of anticancer drugs on healthy cells.

Doxorubicin (DOX) is one of the most commonly used and most effective therapeutic anticancer drugs that has a high potency against of various cancers. In the other hand, DOX like the other anticancer drugs has severe side effects such as gastrointestinal disturbances, nausea, vomiting, hair loss, bonemarrow aplasia and congestive heart failure. As regards to the importance of this matter, there is an urgent need to find the new strategies and materials for targeted drug delivery. In targeted drug delivery systems (TDDSs), suitable carriers can be utilized to protect anticancer drugs from premature degradation in body and also minimize their side effects on normal cells. In this regard, so far a vast range of materials have been used as carrier in TDDSs for cancer therapy, such as polymeric nanoparticlesand vesicles, inorganic materials.