Functionalized DNA Nanogel For Targeted Drug Delivery And Cancer Therapy

Nowadays,the overcoming of cancer is still a difficult and urgent challenge for researchers to achieve,and the existence of malignant tumors is a serious threat to human life and health all the time.At present,traditional therapeutic methods of tumor mainly include radiotherapy,chemotherapy and surgery.However,the above treatment methods have some limitation,which can not completely eradicate the tumor and easily to relapse,especially may cause toxic and side effects of other healthy organs and damage the function of body.Chemotherapy,which is commonly used in clinical application,long-term injection of chemotherapeutic drugs will cause tumor multidrug resistance,thereby inhibiting the progress of tumor therapy.Therefore,how to reverse the multidrug resistance of tumor has become a significant section in the process of tumor therapy.The current research trends in clinical treatment are mostly combining several therapeutic methods,such as utilize chemotherapy and gene therapy for synergistic tumor therapy.Gene therapy can reverse multidrug resistance by silencing the genes related to drug resistance of cancer cells with antisense oligonucleotides drugs,and then use chemotherapy drugs to kill tumor effectively.In addition,the accomplishment of targeting tumor tissue and accurate therapy is always a significant issue in tumor therapy.Gene therapy drugs and chemotherapy drugs themselves do not possess tumor-targeted properties,but will lead to non-ideal therapeutic effects and possible systemic toxicity.Therefore,the targeted and precise delivery of therapeutic drugs requires an appropriate carrier.Ideal nanocarriers with targeted delivery function can not only enrich and accumulate therapeutic drugs in tumor tissue,but also need to be able to controllably release drugs into tumor cells,so as to achieve efficient and low-toxic tumor therapy.As a natural biomacromolecule,DNA has been widely studied and applied in biomedical fields due to its superior biocompatibility and biodegradability.With the development and application of DNA nanotechnology,large quantities of novel drug delivery vehicles with precise nanostructure and controllable size have emerged.In this thesis,a functionalized DNA nanogel was designed and constructed for reversing the multidrug resistance of tumor and accomplishing synergistic therapy,then performed a series of studies.Firstly,we designed and constructed a stimuli-responsive and tumor-targeted DNA nanogel through DNA nanotechnology loading antisense oligonucleotides drug and doxorubicin,and then characterized the fabricated DNA nanogel.Nextly,we estimated the released efficiency of DNA nanogel in response to stimulation in the presence of glutathione and its serum stability.Finally,we evaluated the internalization of DNA nanogel by MCF-7R cells,multidrug resistance related gene silencing effect and the inhibition of cell viability.Through the above research,we found that the designed and constructed functionalized DNA nanogel has a high uploading rate of doxorubicin and antisense oligonucleotide drugs,good serum stability,and effectively responsive release into tumor cells.In addition,the nanogel modified with MUC1 aptamer could apparently improve the efficiency of tumor cellular uptake.The nanogel internalized into the tumor cells could intelligently release the loaded drugs and perform their therapeutic functions in tumor cells,realizing effective synergistic therapy through gene therapy and chemotherapy.