| Due to the high atomic number,gold nanoparticles have excellent X-ray absorption and attenuation ability,which makes them widely studied in the field of biomedicine,especially in radiotherapy and computed tomography(CT)imaging.In terms of tumor radiotherapy,ionizing radiation caused by high-energy rays brings harm to healthy tissues.Currently,radiosensitizers used in clinical practice cannot specifically recognize and remain in tumor,resulting in the the limited radiosensibility.However,gold nanoparticles can be modified with targeted molecules to obtain tumor targeting ability and enhanced radiosensibility,which is beneficial for imaging guided radiotherapy.Moreover,stem cell therapy has brought hope to cure diseases such as neurodegenerative diseases and pulmonary fibrosis.Understanding the migration and homing behavior of stem cells in vivo is of great significance to investigate the mechanism of treatment.However,there is a lack of detection methods for the location of transplanted stem cells in vivo,which hinders the development of stem cell therapy.Gold nanoparticles with good biocompatibility and CT imaging ability can be used for stem cells labeling,so as to get the information of stem cells in vivo noninvasively,which is important for the research on the mechanism of stem cell therapy.This thesis focuses on the synthesis and design of gold nanoparticles for biomedical applications.We first obtained two kinds of gold nanomaterials that can be used for tumor radiosensitizer and mesenchymal stem cell(MSC)tracer,respectively.Then the culture of labeled MSCs on the three-dimensional microenvironment was also studied.Major achievements include:1.Au-Ag@HA NPs—gold nanoparticles coated with hyaluronic acid were applied to the sensitization study of tumor radiotherapy.The results showed that under the combined effect of Au-Ag@HA NPs and X-ray,the number of 4T1 tumor cells clones was significantly reduced,as well as the reactive oxygen was increased and glutathione was exhausted in tumor cells,indicating that Au-Ag@HA NPs had a significant effect of radiosensitization.Further investigation revealed that X-ray irradiation could trigger the release of silver ions in Au-Ag@HA NPs,resulting in cytotoxicity,which may be an important mechanism for the radiosensitization of Au-Ag@HA NPs.2.Au@BSA@PLL—gold nanoparticles coated with poly-l-lysine and bovine serum albumin were designed and synthesized for tracking the transplanted stem cells by CT imaging.The results showed that the growth and potential differentiation capabilities of MSCs labeled with Au@BSA@PLL showed insignificant difference compared with the MSCs without labeling.And the labeled MSCs presented significant contrast of CT imaging in vitro and the endocytosis amount up to 293 pg of gold per cell.The micro-CT imaging in lung showed that Au@BSA@PLL nano-tracer could track the transplanted MSCs for up to 24 days in vivo.3.The GO-PLGA fibrous scaffolds were fabricated for a simulating culture of Au@BSA@PLL labeled stem cells in three-dimensional niche.The results showed that the labeled MSCs were able to maintain the proliferation ability in the scaffold,and their differentiation ability was better than that cultured on the glass slide.It proved the biosafety of tracer-labeled MSCs in a three-dimensional fibrous microenvironment.Furthermore,it also indicated that GO-PLGA scaffolds loaded with MSCs has the potential to be applied in stem cell transplantation. |
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