Design And Synthesis Of Hollow Gold Nanorods And Its Application In Tumor Theranostics

The noble metal nanostructures with plasma properties have shown great prospect in biomedical field,especially the chemically stable Au nanostructures.At present,a variety of Au nanostructures have been prepared and used in biomedical research.However,due to the close relationship between the plasma absorbance peak and their size and morphology,the plasma absorbance peaks of gold nanostructures could hardly be adjusted to the near-infrared region,especially above 1064 nm.In this paper,the Au hollow nanorods(Au HNRs)were prepared by galvanic replacement reaction using Te nanorods as chemical templates,and their applications in biomedicine were further studied.The main research contents and progresses are as follows:(1)Design of gold hollow nanorods with controllable aspect ratio for multimodal imaging and combined chemo-photothermal therapy in the second near-infrared window.The design of novel gold nanomaterials with response in second near-infrared(NIR-II)window is promising in biomedical application.Te nanorods with a controlled aspect ratio were first obtained,and then the Te nanorods were used as chemical templates to react with Au precursor.Under the assistant of cysteine,Au HNRs with an aspect ratio of1.9~6.0 were successfully prepared.Because of the hollow structure,they only need to possess an aspect ratio of 3 to have the absorption peak in the NIR-II window.The photothermal conversion efficiency of the Au HNRs with an absorption peak of about1064 nm at the corresponding laser wavelength is 33%.Experiments show that the Au HNRs have good biocompatibility.Au HNRs have not only been successfully used in photothermal imaging,CT imaging and photoacoustic imaging in tumor-bearing mice,but also showed good effect of chemotherapy-photothermal combined anti-tumor after modifying with an anticancer drug on the surface of Au HNRs.(2)Au hollow nanorods-chimeric peptide nanocarrier for NIR-II photothermal therapy and real-time apoptosis imaging for tumor theranostics.Hollow gold nanorods modified with chimeric peptides can be used to prepare multifunctional nano platform for diagnosis and treatment.We synthesized a chimeric peptide containing photosensitizer and the peptide sequence which can be cut off by caspase-3.Through the surface modification of hollow gold nanorods with the chimeric peptide containing photosensitizer,we obtained theranostic nanoplatform which can be used for photothermal therapy,photodynamic therapy and real-time apoptosis diagnosis.The photosensitizer molecules are quenched before release.After photothermal treatment,the photosensitizer molecules are released from the surface of hollow gold nanorods and reactivated under the presence of caspase-3 enzyme in cell apoptosis,which can realize real-time apoptosis diagnosis.At the same time,the released photosensitizer can be used for photodynamic therapy as a supplement to photothermal treatment.Systematic biosafety studies have proved that it has good biocompatibility and can avoid the phototoxicity of photosensitizer to skin.In vitro and in vivo experiments achieved good therapeutic effect through the combination of photothermal and photodynamic therapy,and in vivo fluorescence imaging realizes real-time monitoring of apoptosis.(3)Miniature hollow gold nanorods with enhanced effect for in vivo photoacoustic imaging in the NIR-II window.Te Se nanorods template with a length of about 46 nm was obtained by improving the preparation method of Te nanorods.M-Au HNRs were prepared successfully by using silver assist in the galvanic replacement reaction.M-Au HNRs have high absorption in the NIR-II window and the photothermal conversion efficiency is 34% at 1064 nm.Experiments show that the material has good biocompatibility.In the in vivo studies,the M-Au HNRs exhibited higher aggregation at tumor sites in tumor-bearing mice than the larger Au HNRs(L-Au HNRs).Moreover,the M-Au HNRs showed better effect in fluorescence imaging after modifying with targeted molecules and fluorescent molecules.Under 1064 nm laser irradiation,the M-Au HNRs showed much better photoacoustic imaging results than the L-Au HNRs.