Journal
NANOSCALE
Volume 7, Issue 40, Pages 16677-16686Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5nr05139h
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Funding
- National Research Foundation (NRF), Prime Minister's Office, Singapore, under its Campus for Research Excellence and Technological Enterprise (CREATE) Programme - Singapore Peking University Research Centre for a Sustainable Low-Carbon Future
- NTU-A*Star Silicon Technologies Centre of Excellence [11235100003]
- NTU-Northwestern Institute for Nanomedicine
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A lot of investigations have been conducted using mesoporous silica nanoparticles (MSNPs) functionalized with different targeting ligands in order to deliver various hydrophobic and hydrophilic drugs to targeted cancer cells. However, the utilization of MSNPs to deliver drug molecules to targeted subcellular organelles has been rarely reported. In this work, we applied targeting ligand-conjugated MSNPs with an average diameter of 80 nm to deliver the anticancer drug doxorubicin (DOX) to mitochondria. Triphenoylphosphonium (TPP) was functionalized on MSNPs as a mitochondria targeting ligand. Mitochondria targeting efficiency was demonstrated in HeLa cells by a co-localization study of mitochondria and functionalized MSNPs as well as by fluorescence analysis in isolated mitochondria. In addition, enhanced cancer cell killing efficacy was achieved when using DOX-loaded and TPP-functionalized MSNPs for mitochondria-targeted delivery. Lowered adenosine triphosphate (ATP) production and decreased mitochondrial membrane potential were observed, demonstrating the mitochondria dysfunction caused by delivered DOX. The positive results indicate promising application potential of MSNPs in targeted subcellular drug delivery.
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