Genetically Multimodal Therapy Mediated By Biodegradable Cationic Nanosystem

Due to the increasing pressures of life and work in today's society,as well as lifestyles that increase the risk of cancer,cancer cases and deaths are increasing dramatically.Although a large amount of manpower,material and financial resources are invested in the development of new cancer treatment methods,due to the uncontrollability,heterogeneity and easy transferability of the tumor,the current traditional single treatment method can only achieve limited success.Therefore,multimodal treatment with hypotoxicity and high efficiency came into being.Multimodal treatments for different diseases have been continuously explored.Among them,photodynamic/gene therapy is a promising treatment strategy of tumor.However,the limitations of traditional chemical photosensitizers and the unsynchronization of the two treatment methods limit the development of this technology.Traditional chemical photosensitizers have some limitations,such as poor hydrophilicity and poor biocompatibility.At the same time,because the plasmid of expression takes a certain amount of time,the photodynamic therapy of the vector and the gene therapy of the plasmid expression often cannot be performed at the same time.In response to the above problems,we propose a dual-mode treatment strategy under gene regulation.In the second chapter of the thesis,first,adamantane modified hydroxyethyl starch(HES-Ad)and low-toxic cyclodextrin-based cationic carrier(CD-PGEA)with good biocompatibility were obtained by supramolecular assembly New polysaccharide-based cationic delivery vehicle(HES@PGEA).Secondly,we design an integrated plasmid(pKR-p53)that can simultaneously express photosensitive protein(KillerRed,KR)and tumor suppressor protein(P53).The delivery of this new type of treatment into the tumor through the designed vector can realize the dual-mode treatment of apoptosis/photodynamic killing under gene regulation.The experimental results indicated that the supramolecular assembled HES@PGEA shows lower cytotoxicity and excellent gene transfection efficiency.This multimodal treatment strategy has demonstrated synergy in in vitro cancer cell suppression experiments and achieved good therapeutic effects in in vivo tumor suppression experiments.Based on the second chapter,the application of the new integrated plasmid pKR-p53 was expanded.We first synthesized a new type of highly efficient degradable guanidine-based cationic gene vector,then mediated a new type of integrated plasmid pKR-p53.The experimental results show that in vitro cell experiments and in vivo tumor inhibition experiments have shown excellent anti-cancer effect.In summary,this excellent gene multimodal nucleic acid delivery system provides a good treatment strategy and ideas for the treatment of tumors and other diseases.