ROS-responsive organosilica nanocarrier for the targeted delivery of metformin against cancer with the synergistic effect of hypoglycemia. Issue 30 (16th July 2021)

• Record Type: Journal Article
• Authors: Yu, Yefei; Chen, Jifeng; Liu, Shuang; Cheng, Du
• Is Part Of: Journal of materials chemistry. Volume 9:Issue 30(2021)
• Page Start: 6044
• Page End: 6055
• Publication Date: 2021-07-16
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/d1tb01143j
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : A ROS-responsive organosilica nanocarrier for the targeted delivery of metformin against cancer with the synergistic effect of hypoglycemia is reported. Abstract : 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.