pH and redox dual stimulate-responsive nanocarriers based on hyaluronic acid coated mesoporous silica for targeted drug delivery

Background: Many efforts have been explored in the last decade to treat colon cancer but nanoparticulate drug delivery systems are making a vital contribution in the improvement of drug delivery to colon cancer cells. Objective: In this review, we attempt to highlight recent advancements in the development of novel drug delivery systems of nanoparticles for the targeted drug delivery to colon. Polymers like Epithelial Cell Adhesion Molecule (EpCAM) aptamer chitosan, Hyaluronic Acid (HA), Chitosan (CS)– Carboxymethyl Starch (CMS), silsesquioxane capped mesoporous silica, Near IR (NIR) fluorescent Human Serum Albumin (HAS), poly(ethylene glycol)-conjugated hyaluronic acid etc. have been discussed by employing various anticancer drugs like doxorubicin, oxaliplatin, paclitaxel, 5-fluorouracil etc. Conclusion: These novel drug delivery systems have been determined to be more efficacious in terms of stability, sustained and targeted drug delivery, therapeutic efficacy, improved bioavailability and enhanced anticancer activity.

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

Cancers ◽

10.3390/cancers13133321 ◽

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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