Preparation Of Multifunctional Carbon Nanotubes And Graphene Oxide And Their Applications In Biological Imaging And Drug Delivery

Carbon nanotubes (CNT) and graphene oxide (GO) have emerged as novelnanomaterials in the biomedical and electrochemical applications. They have beenwidely used as carirers to deliver anticancer drugs, proteins and gene to the tumorsites. Doxorubicin hydrochloride (DOX) is a common cancer drug and it can beattached to the surface of carbon nanotubes and graphene oxide via the n-n stackinginteractions. Over the past decade, the incidence of prostate cancer is increasingdramatically. However, there is still no eiffcient treatment method. Prostate stem cellantigen is a glycoprotein secreted by prostate cancer cells, which can speciifcally bindto the prostate cancer monoclonal antibody. It is a promising targeting site in theprostate cancer diagnosis and therapy. In this thesis, we first modified multi-walledcarbon nanotubes and graphene oxide, then covalently linked monoclonal antibodyand non-covalently attached DOX on the surface. At last，we evaluated thebiocompatibility and cancer therapy eiffciency of the prepared nanocomposites. Wealso found that both of the two kinds of nanocomposites were multifunctional andcould specifically target the PC-3cells. The carbon nanotube nanocomposites couldbe applied in ultrasound/fluorescence dual-mode imaging, while graphene oxidenanocomposites can be applied in Tj-weighted magnetic resonance imaging. Thedissertation is divided into four chapters.In the first chapter, we summairze the structures, properties, surfacemodifications and biological applications of carbon nanotubes and graphene oxide. Atlast，the idea of the dissertation is supposed. In the second chapter, the CNT-PEI(FITC)-mAbpscA multifunctionalnanomaterial was prepared and characterized. We also studied its drug loadingcapacity and release behaviour to the anticancer drug doxorubicin (DOX), the in vitroand vivo cancer therapy and the ultrasound/fluorescence dual-mode imaging function.The synthesized MWCNT-COOH was in good morphology and small size. Theprepared CNT-PEI(FITC)-mAbpscA held good solubility and can be stably dispersedin several physiological solutions. The in vitro expeirments demonstrated thatCNT-PEI(FITC)-mAbpscA had low cytotoxicity and low hemolytic activity. Since theFITC which is attached on the material could emit green light when excited by the X=488nm light, we used flow cytometry and confocal laser scanning microscopy todetect the material, finding that CNT-PEI(FITC)-mAbpscA could speciifcally targetPC-3cells which overexpressed PSCA. Meanwhile, CNT-PEI(FITC)-mAbpscApossessed high echogenic property, we could observe apparent contrast-enhancedultrasound signals both in vitro and in vivo, which indicates thatCNT-PEI(FITC)-mAbpscA could be used to monitor the tumor in real-time. CNT-PEI(FITC)-mAbpscA had a high capacity to load DOX, CNT-PEI(FITC)-mAbpscA/DOXleaked very little under the normal physiological conditions and had the capacity torelease drug in the acidic environment. CNT-PEI(FITC)-mAbpscA/DOX had anexcellent therapeutic effect without causing obvious side effects to the normal tissues.Therefore, CNT-PEI(FITC)-mAbpscA could be used as an effective drug deliverycarrier.In the third chapter, GO-PAMAM(DTPA-Gd)-mAbpscA multifunctionalnanomaterial was prepared and characterized. We also evaluated its biological safetyand explored its application in magnetic resonance imaging in vitro and in vivo. Wethen loaded doxorubicin on the nanomaterial to study its in vivo therapeutic effect.The structure of the prepared graphene oxide is single layer, with good morphologyand small size，and it could be dispersed uniformly in water. We used secondaryantibody and PAGE gel electrophoresis to certify that the monoclonal antibody wassuccessfully immobilized to the GO-PAMAM(DTPA-Gd). The in vitro and in vivobiological safety expeirments demonstrated that GO-PAMAM(DTPA-Gd)-mAbPscA had a low cytotoxicity to cancer cells and the hemolytic activity was nearlynegligibled, and moreover，GO-PAMAM(DTPA-Gd)-mAbpscA would not cause tissueleison in animal bodies. And the nanomateiral showed a good ability to be used a TiMRI contrast agent. We used a confocal laser scanning microscopy to observe thatGO-PAMAM(DTPA-Gd)-mAbpscA could targetdly deliver DOX to PC-3cells whichoverexpress PSCA, and then DOX was released in the cytoplasm and finally enteredinto the nucleus. At last, we found that GO-PAMAM(DTPA-Gd)-mAbp$cA/DOXshowed an excellent cancer therapeutic effect without weight loss of the mice.Therfore, it is expected to become a novel and multifunctional nanomateiral whichcan be used in targetd drug delivery.In the fouth chapter, we summairze the experimental data and results, and thenexplores the biomedical applications of the prepared multitfinctional nanocomposites,and finally makes an outlook about its further application in the future.