Preparation And Study Of Targeted Drug Delivery Imaging System For Combined Chemotherapy And Photodynamic Therapy

In recent years,cancer has become a major disease threatening human life,and the number of cancer deaths is on the rise.Although regular screening,monitoring and early intervention are the best ways to improve prognosis and survival,efforts are needed to find better,more effective,affordable and acceptable cancer treatments that patients can receive.Conventional cancer treatments are chemotherapy,radiotherapy and surgery,and more recently small molecular-based therapies and immunotherapies and combinations of these strategies are being practiced.However,chemotherapy is usually associated with systemic side effects,high recurrence rates are associated with surgical removal of tumors,and radiotherapy is limited by cumulative radiation doses.Photodynamic therapy（PDT）is an alternative approach to tumor ablation and functional preservation,which is often used in combination with chemotherapy and other therapies.Nowadays,designing nano-drug delivery systems and combining multiple therapies is a new approach to cancer treatment.It can effectively inhibit tumor growth,so that its cancer treatment effect can be significantly enhanced.The main research contents of this paper are as follows:1.Herein,we prepared a redox-sensitive nanomicelle drug delivery system PCL-SS-PEG-DTPA-VI-PBA（poly（ε-caprolactone）-ss-poly（ethyleneglycol）-b-poly（diethylenetriaminepentaacetic acid）-b-poly（imidazole）-b-poly（phenylboronic acid））to realize the desirable cancer therapy.It is worth noting that the nanomicelles have multiple functions,including glutathione（GSH）-triggered drug release,in vivo and in vitro cell imaging,and chemo-photodynamic co-therapy.The nanomicelles can deliver anti-cancer drugs（DOX and 5-FU）to B16F10 cells.Redox response was demonstrated by examining the drug release behaviors of the micelles in tumor environment.In addition,to increase the anti-tumor effect,the nanomicelles were loaded with the inorganic photosensitizer Cd Te quantum dots（QDs）and the organic photosensitizer Rose Benga,thus producing high doses of reactive oxygen species（ROS）and realizing PDT.Importantly,Cd Te QDs and ^99mTc were used for fluorescence imaging and SPECT imaging to track the distribution of the drugs in vivo,and phenylboronic acid（PBA）as target substance to sialic acid in tumor sites for active targeting therapy.In vivo experiments showed that the micelles loaded with DOX and5-FU had better anti-tumor effects and reduced systemic toxicity in C57BL mice compared with glutathione-sensitive micelles and free drug solutions.These results fully demonstrated the potential of glutathione-sensitive PCL-SS-PEG-DTPA-VI-PBA micelles in the intracellular transport of anticancer drugs.By these advantages,the synergistic effect of chemotherapy and PDT significantly reduced cytotoxicity,effectively inhibited tumor growth,and enhanced the therapeutic effect of cancer.Taken together,the redox sensitive nanomicelle is a promising tumor drug delivery system with good biocompatibility,low toxicity and high selectivity.2.WeconstructedananomicellePC7A-PEG-DTPA-VI-PBA（poly（2-（hexamethylene imino）ethyl methacrylate）-b-poly（ethylene glycol）-b-poly（diethylenetriaminepentaacetic acid）-b-poly（imidazole）-b-poly（phenylboronic acid））,which could transform charge in different p H solutions.DOX released faster from micelles in a weakly acidic environment（p H 5.0）than at p H 7.4.In order to enhance the anti-tumor effect,the imidazole functional groups in the polymer were used to coordinate CdSeTe QDs for PDT.In addition,the surface of the micelle was further decorated with PBA as a targeting group and DTPA to chelate ^99mTc for SPECT imaging.It has been successfully proved that the nanoparticles have a good cumulative effect on tumor sites.The structure of the polymer was characterized by ¹H NMR.The morphology and particle size of the micelles were characterized by transmission electron microscopy（TEM）and dynamic light scattering（DLS）.The drug loading capacity（DLC）and drug loading efficiency（DLE）of the micelles were analyzed by ultraviolet-visible spectroscopy（UV-Vis）.And the p H sensitivity,drug release and cytotoxicity of the micelles were verified in vitro.In vitro experiments showed that the nanomicelles were noncytotoxic to different cell lines,while DOX@CdSeTe@PC7A-PEG-DTPA-VI-PBA+light inhibited the proliferation and promoted the apoptosis of B16F10 cells.An in vivo study with C57BL tumor-bearing mice indicated that DOX@CdSeTe@PC7A-PEG-DTPA-VI-PBA nanomicelles could efficiently inhibit tumor growth.The results indicate that the nanomicelles has good p H sensitivity and biocompatibility,and the loaded DOX can be released in the weak acidic environment of tumor cells,and it is expected to be a good drug delivery system.3.Nanoscale coordination polymers with inherent biodegradability and chemical diversity are promising nanomaterials in the field of nanomedicine.In this paper,ferrous ion(Fe²⁺)coordination polyallylamine was used as an organic bridge ligand to coordinate DOX which could be release drug in acidic conditions,and a unique p H-sensitive nano-scale coordination polymer was constructed.In addition,Fe²⁺can generate Fenton reaction in the presence of H₂O₂for chemical mechanical treatment.The properties of the polymer were characterized by means of ¹H NMR,TEM,UV,IR,etc.The drug carrier was tested in vivo by cell experiments and animal experiments.The research shows that the nanomicelle has achieved a good anti-tumor effect and will have broad application prospects.