Aptamer-Functionalized Dextran Coated Nano-Graphene Oxide For Targeted Drug Delivery To Breast Cancer Cells

Cancer is the second leading cause of death after heart diseases worldwide. Breast cancer is themost prevalent cancer among women which ranks second for cancer death. Development of chemoresistance is the most pressing major dilemma in cancer therapy. Targeted drug delivery to cancercells could be a promising approach to deliver a higher dose of therapeutics to the specific tumorcells while reducing the associated adverse effects. Aptamers are favorable targeting agents madeof single-stranded, synthetic DNA or RNA molecules which specifically recognize and bind tightly totheir targets due to their secondary or tertiary structure. Nucleolin is a trans membraneglycoprotein highly expressed in the plasma membrane of tumor cells. It is demonstrated that cellsurface nucleolin acted together with protein complexes is associated with tumorgenesis andangiogenesis. To improve the therapeutic efficiency we fabricated a novel functionalizedantiparticle composed of graphene oxide-dextran-AS1411 aptamer and used the complex as adelivery platform for curcumin (which is the main component of Curcuma longa and it is found tohave wide range of medicinal properties such as anticancer and anti-inflammatory effects) againstnucleolin positive breast cancer cells. First of all, graphene oxide was synthesized from graphitepowder using the modified hummers method. Then, it was covalently conjugated to amine modifieddextran and AS1411 aptamer was covalently attached to the surface of the fabricated platform.Thereafter, curcumin which is an aromatic ring-containing drug was loaded onto the surface of thenanoparticle. Physicochemical characteristics of the newly synthesized nanoparticle wasevaluated. Then, release study, cellular viability study and cellular uptake was investigated. TheGO-DEX-Apt-CUR could efficiently enter into 4T1 and MCF-7 nucleolin over-expressed cancer cellsconfirmed by fluorescence microscope and flowcytometry, also it showed significantly highercytotoxicity compared to non-targeted agents. These types of targeted nanoscale drug deliveryvehicles on the basis of DEX coated GO may find potential application in cancer chemotherapy.