Development Of High-Z-Element-Containing Nanostructures For Applications In Cancer Theranostics

Current cancer treatment methods in the clinic including surgery,chemotherapy and radiotherapy(RT),have many limitations such as significant side effects and limited therapeutic efficiency.In order to overcome these problems,nanomaterials with unique physical /chemical properties have been widely explored in cancer diagnosis and therapies.Recently,nanostructures with high-Z elements have shown promises in enhancing radiotherapy because of their strong X-ray attenuation and unique functions in cancer theranostics.In this thesis,two kinds of high-Z-element containing nanostructures have been fabricated and applied in imaging-guided cancer therapy.1.Bottom-up preparation of uniform ultrathin rhenium disulfide(Re S2)nanosheets for image-guided photothermal radiotherapy.Uniform ultrathin Re S2 nanosheets,a new kind of 2D transition metal dichalcogenide,with strong absorption of near-infrared(NIR)light and X-ray are successfully synthesized via a high-temperature thermal decomposition method.After polyethylene glycol(PEG)modification,the PEGylated Re S2 nanosheets show great water solubility and physiological stability.Apart from strong NIR light and X-ray absorption,which could be utilized in photoacoustic imaging and X-ray computed tomography(CT)imaging,Re S2-PEG nanosheets can also be chelator-free labeled with radioisotope ions,99mTc4+ for Single-Photon Emission Computed Tomography(SPECT)imaging.After intravenous injection into tumor-bearing mice,efficient tumor accumulation of Re S2-PEG was observed under triple-modal imaging.Moreover,a remarkable in vivo synergistic effect in the combined photothermal-radiotherapy to destruct tumors was achieved with those Re S2-PEG nanosheets.2.Renal-clearable ultrasmall coordination polymer nanodots for chelator-free 64Cu-labeling and imaging-guided enhanced radiotherapy of cancer.Utilizing the coordination between tungsten ions(WVI)and gallic acid,a new kind of ultrasmall coordination polymer nanodots(W-GA CPNs)was synthesized via a simple method.After surface modification with polyethylene glycol(PEG),the obtained W-GA-PEG CPNs could be stable in various physiological solutions with an ultrasmall hydrodynamic diameter of 5 nm.Moreover,without the help of chelator molecules,radioisotope 64Cu2+ could still be efficiently labeled on the surface of W-GA-PEG CPNs for in-vivo positron emission tomography(PET)imaging,revealing sufficient tumor accumulation and rapid renal clearance of W-GA-PEG CPNs.After intravenous injection of such W-GA-PEG CPNs into tumor-bearing mice,obvious tumor inhibition was observed under radiotherapy due to the radio-sensitizing function of tungsten with strong X-ray absorption.Utilizing the above two high-Z-element containing nanostructures,we have successfully realized imaging-guided cancer therapy with enhanced therapeutic effects,particularly for enhanced radiotherapy of cancer.Our results suggest that such nanostructures may be valuable for applications in cancer theranostics.