Micro-CT Imaging Of RGD Conjugated Gold Nanorods Targeting Tumor In Vivo

Cancer disease is the world’s leading cause of death and early detection of cancer is an effective method of reducing mortality. Looking for effective methods of diagnosis and treatment of tumors has been always the focus of the life sciences community. Computed Tomography(CT), Magnetic Resonance Imaging(MRI), Positron Emission Tomography(PET), Ultrasound Imaging(UI) and dual-mode and multi-modality imaging are among the valuable cancer imaging methods. Despite the advantages, the above methods are unable to overcome its own disadvantages. With the development of nanotechnology, many different structures, shapes and compositions of nanomaterials have been favored in the diagnosis and treatment of tumor. Unlike other nanomaterials, gold nanoparticles have aroused great attention in the field of molecular biology and medicine with its tunable optical properties, easily controlling of surface chemistry, the appropriate nano size and the potential non-cytotoxic.Gold nanomaterials have obtained more and more people’s attention due to its unique optical properties and surface chemical affinity, which gold nanorods(AuNRs) get particular noteworthy. By changing the aspect ratio we can change the two surface plasmon resonance(SPR) absorption peaks which make the biological applications of AuNRs more widely. AuNRs had a good chemical affinity to be modified by a variety of substances which facilitated the preparation of functional nanoprobes. The AuNRs possess great adventages in biological imaging, such as two-photon fluorescence imaging, photoacoustic imaging, optical coherence tomography, X-ray computed tomography etc. Meanwhile, AuNRs have outstanding performance in the photothermal therapy and drug delivery. In short, AuNRs have great potential in imaging, diagnosis and treatment of tumors.In this thesis, gold nanomaterials were used as Micro-Computed Tomography(Micro-CT) contrast agents to get a higher contrast effect at lower X-ray dosage with advantages of longer imaging time and lower toxic side effects compared to current contrast agents. Integrin αvβ3 is a receptor for Arg-Gly-Asp-D-Phe-Lys(RGD) peptide which is over expressed on some tumor cells and tumor neovasculature. In this thesis, we conjugated the RGD peptide on the surface of AuNRs to specifically recognize, target and image the tumor with the help of Micro-Computed Tomography(Micro-CT). The MTT assay and stability measurement showed that RGD-conjugation reduced their cytotoxicity and improved their biocompatibility and stability. Dark-field imaging of U87 cells(integrinαvβ3-positive cells) and HT-29 cells(integrinαvβ3-negative cells) testified the tumor cells binding affinities and uptake abilities of RGD conjugation AuNRs(RGD-AuNRs). The enhanced micro-CT imaging contrast of intramuscular and subcutaneous injection illustrated the feasibility of RGD-AuNRs to be contrast agents. Furthermore, the micro-CT imaging of targeting U87 and HT-29 tumor models verified the targeting abilities of RGD-AuNRs and the tumor uptake of RGD-AuNRs was determined by integrin αvβ3 expression level of tumor cells.With a higher expression of integrin αvβ3 a better imaging effect would get. RGD-AuNRs nanoprobe is a promising candidate in applications such as tumor targeting and imaging capability for micro-CT imaging.