The Preparation And Application Of Metal-organic Self-Assembly-based Phototherapy Enhancement Nanomedicine

Nanomedicines have been widely studied in molecular imaging and optical therapy,but nanomaterials have limited clinical applications due to biological toxicity.Preparing nanomedicine with excellent biocompatibility,outstanding photo-therapy and high disease area enrichment was a good way to solve this problem.In this thesis,we fabricated nanomedicine using clinical study small molecule drugs to extend the application of photo-therapy,and promoted the clinical research of the nanomedicine.The main research are as follows:(1)In Chapter 1,we introduced the current status of nanomedicine,and introduced the application of the nanomaterials-based drug delivery systems.By studying the different preparation methods of metal organic nanostructures and the research status of the metal-organic nanoparticles(MONs)applied in the diagnosis and treatment of disease,we determined thestudy of MONs using Metal ions and photosensitizers.Under the guidance of molecular imaging technology,the photo-therapy of MONs was realized.(2)In Chapter 2,we studied the photodynamic effect of a photosensitizer(sinoporphyrin sodium,DVDMS).Considering the molecular structure of the DVDMS,we studied the interaction between the DVDMS and Mn2+.We found that with the addition of the Mn2+,the absorbance and the photodynamic effect was enhanced,and the photothermal effect appeared.With the study of the DVDMS and Mn2+supramolecular assembly,we prepared DVDMS and Mn2+-assemblied nanotheranostics(Mn/DVDMS).This unique nanostructure enabled good phtoto-therapy for the cancer cells.Our prepared Mn/DVDMS should showed one direction for the clinical study of DVDMS.(3)In Chapter 3,we prepared manganese dioxide(MnO2)nanosheets served as a highly effective DVDMS carrier.In addition,our prepared MnO2/DVDMS could decomposed by H2O2(in acid solution)and glutathione(GSH)with the release of Mn2+,and the DVDMS and Mn2+ re-assembled into Mn/DVDMS.In cancer cells and xenograft tumors,MnO2/DVDMS also could re-assembled into Mn/DVDMS.And,the MnO2/DVDMS interacted with H2O2 and GSH,the O2 was produced and GSH was decreased of GSH,resulting of the enhancement of photo-therapy.This tumor microenvironment-triggered re-assembly strategy could offer a new avenue for cancer theranostics.(4)In Chapter 4,we studied the interaction between the indocyanine green(ICG)and Zn2+,and we found that the ICG and Zn2+-assemblied nanostructure(Zn/ICG).Furthermore,instead of Zn2+ we prepared ICG nanostructure(nanoICG)using dipicolylamine-Zn(?)(DPA-Zn)reacted with ICG.Afterwards,the nanoICG was modified with RGD on its surface,following with the enhanced delivery property of survivin-siRNA(S-siRNA).Our prepared nano-composites possessed the combination therapy property of photothermal therapy and gene therapy,and eliminate the tumor due to the combination therapy.(5)In Chapter 5,in the ocular new blood vessels,the survivin proteins could inhibit cell apoptosis,promote cell division and enhance angiogenesis,and the surviving could further promote angiogenesis by up-regulation of VEGF.Considering this,we investigated the combination therapy of photothermal therapy and gene therapy to the ocular angiogenesis using the R-nanoICG/S-siRNA.Through the gene therapy effect of the R-nanoICG/S-siRNA,the survivin and VEGF were down-regulated,and inhibit the regeneration of blood vessels.Furthermore,due to the effect of the photothermal therapy,the new blood vessels were eliminated.All in all,the combination therapy could treat the ocular angiogenesis effectively.