Functionalized Graphene Oxide For Tumor Markers Detecting And Anticancer Drugs Targeted Delivery

Malignant tumor was a serious threat to human health. People had been trying to find a simple, rapid and accurate method for early diagnosis of tumors. The discovery of tumor makers, which could not only be used as a secondary diagnosis of tumor but also detect the recurrence or metastasis of tumors, providing an efficient path for early diagnosis of tumors. Currently, chemotherapy was still one of the most effective approach to tumor treatment. However, the antitumor drugs had less selectivity, so that most therapeutic drugs were uptaken by normal tissues, well very less by tumors, which producing the adverse toxic side effects to healthy tissues. To solve the problem of tumor chemotherapy, the tumor targeted drugs delivery systems need to be developed.Graphene was the most thin two-dimensional nanomaterials so far with benzene ring as its basic structure which was the most stable structure of organic materials. The most studied graphene in biomedical field was functional graphene oxide (GO). GO with carboxy, hydroxy and epoxy groups had good dispersibility, water solubility and stability. Other groups or biomolecules could be introduced to GO not only by acylation and esterification reactions but also by π-π stacking and hydrogen bonding. Studies showed that GO had quenching effect to fluorescent materials and could be a good energy acceptor in FRET system to provide a platform for biosensors. Meanwhile, GO was constituted by maonolayer of carbon atom and had a large surface for drug delivery via π-π stacking with aromatic drug. Thus, GO had been used for detecting biomolecules and targeting delivery of antitumor drugs. The article was carried out as follows on the basis of excellent features of GO mentained above: (1) A FRET probe was constructed for the detection of tumor marker MMP-2using GO as energy acceptor. GO was first prepared by the Hummers method and modified by a peptide with biotin at C terminal which was recognized specifically by MMP-2. The biotin could combine SA-QDs to making GO-Pep-QDs probe.(2) DOX was loaded onto GO nanocarriers via π-π stacking. Then modified HA modified was coated onto GO-DOX, producing a HA-GO-DOX nanohybrid. We had characterized the stucture of HA-GO-DOX and it had good storage stability. Cumulative DOX release from HA-GO-DOX was faster in pH5.3than in pH7.4PBS buffer, providing the basis for controllable DOX release in tumor cells. The cellular uptake study illustrated that this HA-GO-DOX nanocarrier significantly enhanced DOX accumulation and induced selective cytotoxicity in target cells (CD44-positive), but not nontarget cells (CD44-negative). These studies suggest that HA and GO are a promising carrier candidate for antitumor drugs for clinical targeted therapeutic applications.