Stepwise-Acid-Active Multifunctional Mesoporous Silica Nanoparticles for Tumor-Specific Nucleus-Targeted Drug Delivery

2014 ◽  
Vol 6 (16) ◽  
pp. 14568-14575 ◽  
Author(s):  
Ze-Yong Li ◽  
Yun Liu ◽  
Jing-Jing Hu ◽  
Qi Xu ◽  
Li-Han Liu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Targeted Drug Delivery ◽  
Mesoporous Silica Nanoparticles ◽  
Targeted Drug

scholarly journals ADAM9-Responsive Mesoporous Silica Nanoparticles for Targeted Drug Delivery in Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3321
Author(s):  
Etienne J. Slapak ◽  
Lily Kong ◽  
Mouad el Mandili ◽  
Rienk Nieuwland ◽  
Alexander Kros ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Conditioned Medium ◽  
Drug Delivery System ◽  
Delivery System ◽  
Targeted Drug Delivery ◽  
Mesoporous Silica Nanoparticles ◽  
Pdac Cell ◽  
Targeted Drug

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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