Preparation And Functionalization Of Dendrimer-Stabilized Gold Nanostars For Tumor Theranostics

With the development of nanotechnology and nanomedicine,investigation of versatile nanomaterials that favor diagnostic and therapeutic functions within a single nanoplatform is extremely important for both fundamental and clinical medical sciences.Due to the tunable size and shape,gold nanostars(Au NSs)denmonstrate remarkable optical and photothermal properties,and can be used as nanoprobe for molecular imaging such as X-ray computer tomography(CT)and photoacoustic imaging(PA),and photothermal therapy(PTT)of tumor,therefore emerging as a versatile theranostic nanoplatform in early-stage diagnosis and therapy of tumors.Meanwhile,combination or synergistic treatment has become one of the most important strategies to improve the therapeutic efficiency of tumor.In our previous work,several kinds of core-shell nanocomposites with core of Fe3O4 nanoparticle(NPs)and shell of Au NSs(Fe3O4@Au NSs)were fabricated for MR/CT imaging and PTT of tumors.However,these core-shell nanocomposites had a relatively large size and only were able to realize a single mode treatment,limiting their potentials in biomedical applications.In this thesis,we attempted to synthesize nanomaterials with a smaller size for enhanced theranostics or synergetic therapy of tumors.In chapter 2,we first synthesized cyclic RGD-modified amine-terminated generation 3.0 poly(amidomine)dendrimer-stablized gold nanostars(RGD-Au DSNSs)and then RGD-Au DSNSs were used as gene carrier and cultured with si RNA to form nanocomposites of RGD-Au DSNS and si RNA for CT imaging,PPT and gene therapy of tumor.The results demonstrate that the formed RGD-Au DSNSs are water soluble,colloidally stable,biocompatible,and possess a high X-ray attenuation cofficient.The cell results show that with the presence of RGD peptide,the nanocomposites can efficiently carry VEGF si RNA into human brain glioma cells(U87MG cells),and the viability of cells incubated with RGD-Au DSNS/si RNA was only 20.2% after NIR irradiation,which is much lower than that under single PTT or gene therapy.In vivo results reveal that the RGD-Au DSNS/si RNA enabled an effective CT imaging of tumor.Meanwhile,the tumor size measurement and the histological examination after intratumoral injection and laser exposure demonstrate that the tumor inhibition effect of the RGD-Au DSNS/si RNA is better than all other groups,indicating that the therapeutic effect of combined PTT and gene therapy is more effective than single therapy.All these results indicate that the developed multifunctional nanostructure is a promising platform for tumor theranostics.In chapter 3,in order to enhance the treatment effect of tumor,we synthesized the 131 I labeled Au DSNSs-based multifuctional nanoprobe via 3-(4'-hydroxyphenyl)propionic acid-OSu(HPAO)for photothermal and radiation combination therapy of tumor.The results show that the formed nanoprobe possess good colloidal stability,monodispersity,radiolabeling stability and biocompatibility.In vitro cell results demonstrate that the cells treated with 131 I labeled Au DSNSs(Au-131I-G3-HPAO DSNSs)have the lowest viability after laser exposure than other cell groups after single photothermal or radiation treatment,indicative of the enhanced synergetic therapeutic effect of tumor.In vivo results reveal that the formed Au-131I-G3-HPAO DSNSs possess the ability of SPECT/CT dual mode imaging of tumors.All these results indicate that the developed multifunctional nanomaterial can be used for tumor theranostics.In summary,we extensively explored the synthesis and further functionalization of a multifunctional dendrimer-stablized gold nanostar nanoplatform to enhance the diagnostic accuracy and therapeutic efficiency.The findings from this thesis provided new thoughts to develope novel and accurate contrast agents and establish a new platform for tumor theranostics.