采用非浸润模板制作纳米颗粒基因药物

RNA-based Drug Delivery via PRINT Nanoparticles

近年来,RNA(Ribonucleic Acid,核糖核酸)干扰现象在癌症、病毒感染治疗方面展现出巨大潜力。RNA干扰药物可以直接作用于致病基因,治疗作用更加彻底,治疗范围更加广泛,同时降低了的副作用。RNA药物研究工作中遇到的最大困难就是将敏感易分解的基因药物传输到哺乳动物细胞中。美国北卡罗来纳大学实验组致力于采用PRINT(Particle Replication in Non-wetting Templates,在非浸润模板中制作纳米颗粒)技术制作大小形状均一可控的纳米级颗粒来运载基因药物。实验中通过测定HeLa癌症细胞中的荧光素酶降低率以及细胞存活率来评价PRINT颗粒的运载效果。最终制得运载效率为65%的PVP(Poly(N-vinyl pyrrolidone,聚乙烯吡咯烷酮)PRINT颗粒。

RNA interference has the potential to become the basis for a broad class of important therapeutics for virus infection,cancer and other diseases. However,in vivo delivery of nucleic acids,such as small interfering RNA （siRNA）,to the cells of choice in mammals continues to constitute one of the key hurdles to successful use of this technology. The objective of our work is to exploit the Particle Replication In Non-wetting Templates （PRINT） process to prepare and deliver uniform polymer nanoparticles containing siRNA. Particles for the studies reported in this prospectus are constructed of lightly crosslinked poly（vinyl pyrrolidone） （PVP）. Particle chemical composition with 30 wt% disulfide crosslinker showed higher knockdown and the best knockdown efficiency we obtained so far is 65%.