摘要
Objective:Although great progress has been made in the field of siRNA gene therapy,safe,efficient,and targeted delivery of siRNA are still major challenges in siRNA therapeutics.Methods:We developed an up-conversion nanoparticle-based nanocage system.This system protected the siRNA from being degraded by nucleases in organisms and selectively delivered the siRNAs to the tumor sites,due to modifications of targeted molecules on the surfaces of nanocages and local inhalation.Results:The siRNAs delivered by the up-conversion nanoparticle nanocages were protected from degradation in transit to the tumor sites,where they accumulated.Compared with the passive target and control groups,the up-conversion nanoparticles based on the nanocage system showed a tumor suppressive effect after approximately 3 weeks of treatment.Conclusions:The up-conversion nanoparticle nanocages efficiently delivered vascular endothelial growth factor siRNAs to tumor sites.Mice with lung tumors treated with tumors targeting up-conversion nanoparticle nanocages showed steady body weight changes,high tumor inhibition ratios,and longer survival times.
基金
supported by the National Key Basic Research Program(973 Project)(Grant Nos.2015CB931802 and 2017FYA0205301)
the Special Fund for Science and Technology Innovation of Shanghai Jiao Tong University(Grant Nos.YG2017MS70,YG2015MS62,and AF0300179)
the Shanghai Municipal Bureau of Economy and Information Technology(Grant No.XC-ZXSJ-02-2016-05)
the National Natural Scientific Foundation of China(Grant Nos.8202010801,81921002,81225010,81028009,and 31170961)
the 863 Project of China(Grant No.2014AA020700)
and the Shanghai Science and Technology Fund(Grant No.13NM1401500)。
