期刊
JOURNAL OF MATERIALS CHEMISTRY B
卷 9, 期 30, 页码 6044-6055出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1tb01143j
关键词
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资金
- National Natural Science Foundation of China [21875289]
- Guangdong-Hong Kong Joint Innovation Project [2016A050503026]
- Major Project on the Integration of Industry, Education and Research of Guangzhou City [201704030123]
A novel ROS-responsive organosilica nanocarrier was successfully synthesized for drug delivery, which exhibited enhanced tumor transport capability through targeting peptide modification. The nanocarrier significantly increased tumor sensitivity to metformin when combined with fasting therapy by down-regulating pro-survival proteins, suggesting its potential as a promising platform for combinatorial therapy.
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 pGSK3 beta 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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