A Nano-Confined Assembly Strategy For The Construction Of Efficient SiRNA Delivery Vector And Cancer Therapy

With the development of RNAi research in recent years,si RNA,as a kind of gene medicine,has shown amazing potential in the field of disease treatment.The characteristics of si RNA,such as high specificity,high safety,and high efficiency,bring new light for the development of cancer drugs.However.the delivery of si RNA in vivo still facing many barriers,such as the system clearance,poor cellular uptake,and the difficulty of reaching the effective concentration in the tumor site.The development of an efficient si RNA delivery platform is a viable solution,which has been reported in lots of researches.In this project,a new nano-confined assembly strategy for the construction of an efficient si RNA delivery platform?S-NCN?has been developed through the careful design of material structure and preparation methods.The efficiency of S-NCN_{si RNA} was reflected in the following two aspects:1)a novel nano-confined assembling strategy for efficient binding between carrier and si RNA,which reduced the use of cationic materials by 60%.2)When S-NCN_{si RNA} reached the tumor environment,the p H-sensitive CDM bonds broke and PAMAM-si RNA complex separated from the main part of nanoparticles to achieve a better uptake by cancer cell.In the experimental part,the corresponding materials were synthesized for the constrution of S-NCN system at first and the functionality of S-NCN was verified.In vitro,it has been demonstrated that S-NCN_{si Plk1} effectively knocked down the expression of Plk1 in MDA-MB-231 cells,and leaded to significant apoptosis of tumor cells.In vivo,S-NCN_{si Plk1} system significantly knocked down the expression of Plk1 and inhibited the growth of human breast cancer cells in nude mice.Finally,S-NCN_{si PD-L1} system combined with adriamycin significantly inhibited the growth of the tumor and improved the immune-suppressive microenvironment.We have developed and proved that S-NCN system is a very potential delivery platform that can effectively bind si RNA and deliver it to target tumor cells,solve the main obstacles of si RNA delivery in vivo and effectively silence target genes.