Hyaluronic Acid Oligosaccharide Modified Redox-Responsive Mesoporous Silica Nanoparticles for Targeted Drug Delivery

2014 ◽  
Vol 6 (22) ◽  
pp. 20290-20299 ◽  
Author(s):  
Qinfu Zhao ◽  
Hongjian Geng ◽  
Ying Wang ◽  
Yikun Gao ◽  
Jiahao Huang ◽  
...  
2014 ◽  
Vol 2 (40) ◽  
pp. 7009-7016 ◽  
Author(s):  
Srivardhan Reddy Gayam ◽  
Shu-Pao Wu

Herein, redox responsive Pd(ii) templated rotaxane nanovalve capped mesoporous silica nanoparticles were designed for an effective cancer-targeted drug delivering system.


2013 ◽  
Vol 19 (5) ◽  
pp. 1778-1783 ◽  
Author(s):  
Zhaowei Chen ◽  
Zhenhua Li ◽  
Youhui Lin ◽  
Meili Yin ◽  
Jinsong Ren ◽  
...  

Nanoscale ◽  
2013 ◽  
Vol 5 (1) ◽  
pp. 178-183 ◽  
Author(s):  
Meihua Yu ◽  
Siddharth Jambhrunkar ◽  
Peter Thorn ◽  
Jiezhong Chen ◽  
Wenyi Gu ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3321
Author(s):  
Etienne J. Slapak ◽  
Lily Kong ◽  
Mouad el Mandili ◽  
Rienk Nieuwland ◽  
Alexander Kros ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate of all cancers. This poor prognosis results from the lack of efficient systemic treatment regimens, demanding high-dose chemotherapy that causes severe side effects. To overcome dose-dependent toxicities, we explored the efficacy of targeted drug delivery using a protease-dependent drug-release system. To this end, we developed a PDAC-specific drug delivery system based on mesoporous silica nanoparticles (MSN) functionalized with an avidin–biotin gatekeeper system containing a protease linker that is specifically cleaved by tumor cells. Bioinformatic analysis identified ADAM9 as a PDAC-enriched protease, and PDAC cell-derived conditioned medium efficiently cleaved protease linkers containing ADAM9 substrates. Cleavage was PDAC specific as conditioned medium from leukocytes was unable to cleave the ADAM9 substrate. Protease linker-functionalized MSNs were efficiently capped with avidin, and cap removal was confirmed to occur in the presence of PDAC cell-derived ADAM9. Subsequent treatment of PDAC cells in vitro with paclitaxel-loaded MSNs indeed showed high cytotoxicity, whereas no cell death was observed in white blood cell-derived cell lines, confirming efficacy of the nanoparticle-mediated drug delivery system. Taken together, this research introduces a novel ADAM9-responsive, protease-dependent, drug delivery system for PDAC as a promising tool to reduce the cytotoxicity of systemic chemotherapy.


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