Structure Design And Drug Release Performance Of Graphene Oxide Supported Anticancer Drugs

In comparison with carrier-free drugs,loaded drugs can strikingly improve therapeutic effect and significantly reduce side-effects,benefitted from these advantages:increased solubility,improved biocompatibility,better dispersion stability,reduced drug precipitation,better sustained release of drugs,controllable release sites.Particularly,these novel drug-release carriers which exhibit the microenvironmental differences between the tumor and normal tissues,have played a vital role in cancer therapy.Recently,graphene oxide（GO）as a novel drug-release carrier,has attracted enormous research interests due to its excellent physical and chemical properties.Moreover,GO composed of a single-layer of sp2 hybrid carbon atoms could easily interact with aromatic anticancer drugs via aπ-πinteraction.In this dissertation,GO-based anti-cancer drug-release carriers for effectively hosting anti-cancer drugs:doxorubicin（DOX）and paclitaxel（PTX）were rationally designed and show controllable drug release behavior.Besides,properties of these controlled-release systems were systematically investigated,including pH-response,reduction-response and magnetic-response.The main conclusions are as follow:（1）The loading and release behavior of DOX from nano-sized GO sheets prepared via a modified Hummers method was systematically studied.Specifically,nano-sized GO sheets with good dispersibility in water exhibit drug loading of 1126 mg/g for DOX.Moreover,DOX/GO performs over 16 h of smooth release time and as high as 82.4%of cumulative release.Meanwhile,cytotoxicity tests demonstrate the good biocompatibility of DOX/GO and its good ability for killing cancer cells as well.（2）A new drug-release carrier Fe₃O₄/GO magnetic composites were fabricated via a simple mixture of GO sheets and monodisperse superparamagnetic Fe₃O₄ nanoparticles to systematically investigate theirs loading and release behavior for DOX.It is significant that Fe₃O₄/GO composites perform 20.6 emu/g of saturation magnetization,60.3%of loading rate,30 h of sustained release time and 45.8%of cumulative release.Furthermore,Fe₂O₃/GO composites show good biocompatibility and outstanding ability of killing cancer cells confirmed via cytotoxicity tests.（3）An amidation reaction was employed to obtain a GO-based drug-release carrier modified with folic acid（FA）and polyethylene glycol（PEG）.The investigation,loading and release behavior for PTX from GO-FA-PEG,indicates 27.4%of drug loading rate,150 h of drug sustained release time and 31.2%of cumulative release rate.Furthermore,GO-FA-PEG as a safe drug-release carrier exhibits remarkable tumor cell targeting and cancer cell killing ability proven via cytotoxicity experiments.（4）Alginic acid（ALG）functionalized by PEG was modified onto GO sheets via a disulfide bond（Cyd）to obtain GO-Cyd-ALG-PEG carrier for loading PTX.The investigation,the loading and release behavior of PTX from GO-Cyd-ALG-PEG in a simulated tumor environment,shows that the drug sustained release time and cumulative release rate of GO-Cyd-ALG-PEG could be up to 80 h and 85.6%respectively Besides,the drug-loaded release system exhibits a significant killing ability toward cancer cells.（5）The loading and release behavior of PTX from a spherical gelatin nanocarrier composed of GO and hydroxypropyl-β-cyclodextrin（HP-β-CD）displays 14.9 mg/g of drug loading and 59.5%of drug loading rate.Besides,the cytotoxicity tests show the relative safety of GO/HP-β-CD gelatin nanospheres and its remarkable ability of killing cancer cells.