体内
生物物理学
药物输送
PEG比率
化学
纳米颗粒
细胞毒性
核心
体外
靶向给药
聚乙二醇化
材料科学
生物化学
纳米技术
细胞生物学
聚乙二醇
生物
生物技术
经济
财务
作者
Fan Yang,Chunyan Li,Fuyou Li,Daoyong Chen
出处
期刊:Biomaterials
[Elsevier]
日期:2016-04-01
卷期号:85: 30-39
被引量:68
标识
DOI:10.1016/j.biomaterials.2016.01.057
摘要
Nucleus-targeted drug delivery is a promising strategy for anticancer therapy, but in vivo nucleus-targeted drug delivery has been challenging. Limited by the channel size of the nucleopore, vehicles that enter the nucleus via the nucleopore actively should be small and decorated with nuclear localization signal (NLS). However, the small vehicle size may promote leakage of vehicles into normal tissues, and the positively-charged NLS can lead to strong non-specific interactions in vivo. In the present study, we demonstrate an in vivo nucleus-targeted drug delivery using large compound nanoparticles with detachable PEG shell. The nanoparticles are composed of PEG-benzoic imine-oligo-l-lysine/iridium(III) metallodrug complex and formed in a kinetically-controlled fashion. Under physiological conditions (pH 7.4), the nanoparticles are large (ca. 150 nm) and protected by an inert PEG shell. When internalized into intracellular acidic endo/lysosomes of cancer cells, the nanoparticles dissociate into smaller ones (ca. 40 nm) and the PEG chains detach due to the cleavage of the benzoic imine bond at low pH. The small nanoparticles, with exposure of the oligo-l-lysine after the detachment of the PEG shield, then translocate into the nucleus via the nucleopore due to the small size and nuclear localization ability of the oligo-l-lysine. Importantly, the small particles could significantly release the contained drug into the nucleus, leading to ca. 20-fold higher cytotoxicity compared to the native drug in vitro. Further in vivo application of the nucleus-targeting nano-system in a nude-mice model showed significant tumor inhibition and remarkable life-span elongation.
科研通智能强力驱动
Strongly Powered by AbleSci AI