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The Synthesis Of Novel Nanomedicines And Its Antitumor Application Research

Posted on:2020-12-29Degree:MasterType:Thesis
Country:ChinaCandidate:Y JinFull Text:PDF
GTID:2381330596985422Subject:Organic Chemistry
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Malignant tumor is one of the serious threat to human health.There are surgical resection,chemotherapy and radiotherapy in the clinical treatment.These methods play a very important role in the treatment of cancer,but they all have certain limitations.Currently,there is no effective method to achieve the cure of malignant tumor.With the development of the study,researchers found that there is a hypoxic area inside the solid tumor,which will induce tumor tolerance to radiotherapy and chemotherapy.In addition,immunotherapy relies on autoimmunity to achieve tumor treatment,which can kill both in situ and metastatic tumor.The emergence of nanotechnology has provided more strategies for the treatment of tumor in recent years.Nanomedicine has more biologically effective than traditional drugs in chemotherapy and immunotherapy owing to its characteristics,such as stable,low-dose,high-efficiency and targeting ability.It can achieve more goals which cannot be achieved by traditional drug delivery methods.Herein,we fabricated two nano-systems for treating malignant tumor.The first one can realize the co-delivery of glucose oxidase?GOx?and hypoxia-activated prodrugs,which can achieve synergistic treatment for hypoxia tumor.The other one can inhibit tumor growth via immunotherapy.In terms of chemotherapy,we designed a nanosystem based on glucose oxidase?GOx?and hypoxia activated prodrug?TPZ?.Firstly,TPZ was loaded into mesoporous silica?MSN?,and further encapsulated inside carMOF formed by Fe3+and carbenicillin,which can avoid the early release of the TPZ.Then,GOx was adsorbed on the surface of carMOF to form the final material MSN-TPZ@carMOF-GOx.MSN-TPZ@carMOF-GOx can consume glucose and O2 for futher activating TPZ,which would achieve synergistic cancer therapy with starvation and chemotherapy.A series of experimental in vitro and in vivo has been conducted,and the results demonstrate that the nanosystem was successful constructedand had been successful used to treat tumor.In terms of immunotherapy,we designed a traceable tumor vaccine based on up-conversion nanomaterials?UCNPs?and ovalbumin?OVA?.According to literatures,we synthesized UCNPs and OVA-modified nanogold clusters?Au-OVA?,which were further linked by alendronate sodium?ALN?and terephthalaldehyde?TPDA?.The imine bond formed by TPDA and OVA would break under acidic conditions and release OVA,which will further activate the immune system of the body and kill tumor cells.A series of experiments have proved that the system has achieved good results in the treatment of melanoma.
Keywords/Search Tags:nanomedicines, chemotherapy, Cancer vaccine, Tirapazamine, Ovalbumin
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