纳米载体
二甲双胍
体内
活性氧
表面改性
药理学
药物输送
纳米颗粒
体外
化学
药品
生物物理学
材料科学
纳米技术
癌症研究
医学
生物化学
糖尿病
内分泌学
生物
生物技术
物理化学
作者
Yefei Yu,Jifeng Chen,Shuang Liu,Du Cheng
摘要
The controllable degradation of silica nanoparticles in anticancer therapy remains challenging. Here, we offer the first report that a thioketal (TK)-bond-containing bridged organoalkoxysilane has been synthesized. This allows for the fabrication of reactive oxygen species (ROS)-sensitive, degradable, bridged silsesquioxane nanoparticles (BS-NPs). These TK-bridged BS-NPs have a uniform size of 50 nm and are able to encapsulate a small molecule drug - metformin - using a reverse micro-emulsion method. After surface modification with a targeting peptide (RGD), these metformin-loaded BS-NPs exhibited a homologous tumor aggregation ability, leading to the efficient transport of metformin into the tumor cells. When combined with a clinically feasible fasting therapy, the RGD-decorated, metformin-loaded, ROS-responsive degradable BS-NPs remarkably increased the tumor sensitivity to metformin by 10 times compared with free metformin. The synergistic effects of metformin-loaded BS-NPs and fasting-induced hypoglycemia were verified through in vitro and in vivo experiments. This effect occurred by down-regulating the expression of pro-survival proteins pGSK3β and MCL-1. Collectively, these results demonstrate that the ROS-sensitive organosilica nanocarrier is a promising nanoplatform for drug delivery and provides an alternative approach for the combinatorial therapy of metformin and fasting therapy.
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