Formation Of Gold Nanostar-coated Hollow Silica Nanoparticles For Multi-modal Theranostics Of Tumor

Development of multifunctional nanoplatform for multimodal diagnosis and therapy is a research hotspot in the field of nanomedicine.Due to the excellent size controllability,unique mesoporous and cavity structure,and facile surface functionalization,hollow mesoporous silica nanoparticles(HMSs)have been extensively utilized for ultrasound imaging(US),drug delivery,high intensity focused ultrasound(HIFU)therapy or nuclear targeted therapy.In order to improve the sensitivity of diagnosis and the efficiency of therapy for tumors,different HMSs loading or coated by various nanoparticles(such as Au NPs,Fe3O4 NPs and Mn oxides)or/and anticancer drugs(such as DOX,paclitaxel and a-TOS)have been developed and widely used for molecular imaging or therapy of tumors,such as US imaging,X-ray computer tomography(CT),magnetic resonance imaging(MR),photoacoustic imaging(PA),near infrared imaging(Thermal imaging),chemotherapy and photothermal therapy(PTT).Literatures show that HMSs possess excellent drug loading capacity and controllable and sustainable drug release feactures.In addition,Au NPs-coated and PFH-entrapped HMSs have been successfully used for dual-modal US/CT imaging and HIFU therapy of tumor.Furthermore,our previous work showed that polyethyleneimine(PEI)-coated Fe3O4/Au nanostars(NSs)core/shell nanocomposite were able to be fabricated for multimodal MR/CT/PA imaging and simultaneously for PTT of tumor due to the absorption in near infrared(NIR)region of Au NSs.Based on these work,two type of HMSs@Au NSs containing different gold content were successfully prepared and used as carriers to load imaging element or anticacer drug for theranostics or synergetic therapy of chemotherapy and PPT of tumor,respectively.In chapter 2,HMSs were first synthesized,modified with thiol groups and successively conjugated with Au NPs.Then the formed HMSs@Au NPs were used as seeds to produce HMSs@Au NSs in an Au growth solution.After that,the generated HMSs@Au NSs were utilized as templates to encapsulate liquid PFH,followed by surface modification with m PEG-SH.At last,the formed HMSs@Au-PFH-m PEG NSs(HAPP)were used for multimodal US/CT/PA/thermal imaging and PTT of rat glioma cell(C6)xenotransplanted tumor model.The results show that HAPP with size of about 250 nm had high surface area,good stability and excellent biocompatibility,and displayed strong ultrasonic echo signal,superior X-ray attenuation performance,high photoacoustce signal intensity and excellent photothermal conversion efficiency.The in vitro and in vivo imaging results showed that the HAPP were able to be used for the multimodal US/CT/PA/thermal imaging of tumors,resulting in an improved the diagnostic sensitivity.The in vivo and in vitro photothermal ablation revealed that HAPP with high photothermal conversion efficiency can be applied to PTT of tumor.Therefore the formed HAPP can realize diagnosis and therapy of tumor using the same nanoprobe.In chapter 3,in order to further improve the therapeutic efficiency of tumor,the HMSs@Au NSs with larger gold content were first prepared,and modified with polyethylene glycol(PEG)with one end of thiol and the other end of RGD peptide(SH-PEG-RGD).The formed HMSs@Au-PEG-RGD NSs were then used as the template to encapsulate DOX and at last DOX-loaded HMSs@Au-PEG-RGD were investigated for targeted synergetic therapy of chemotherapy and PPT using U87 MG xenotransplanted tumor model.The results showed that the size of HMSs@Au-PEG-RGD NSs is about 270 nm,which has good stability and biocompatibility,high drug load efficiency,and excellent targeting ability of U87 MG cells over expressing ?v?3 integrin.In vitro drug release results showed that HMSs@Au-PEG-RGD NSs/DOX displayed the p H/NIR laser dual-responsive DOX release behavior.The photothermal ablation in vitro and PTT in vivo showed that HMSs@Au-PEG-RGD NSs/DOX possessed high photothermal conversion efficiency due to the increased gold content and could achieve synergetic therapy of chemotherapy and PTT of tumor,resulting in enhanced anticancer efficiency.In summary,we synthesized two types of HMSs@Au NSs with different gold content and the formed HMSs@Au NSs were used as templates to load imaging element or anticancer drug.Along with suitable multifunctionalization,the imaging element-or anticancer drug-loaded HMSs@Au NSs can be used to achieve multi-modal imaging and PTT of tumor or combined therapy to improve the diagnosis sensitivity and therapy efficiency of tumor.The research ideas and findings of this thesis provide a new thought to develope novel,multifunctional,highly sensitive and efficient nanoplatform for theranostics and synergetic therapy of tumor.