Cancer-Cell-Specific Mitochondria-Targeted Drug Delivery by Dual-Ligand-Functionalized Nanodiamonds Circumvent Drug Resistance.
Miu Shan ChanLing Sum LiuHoi Man LeungPik-Kwan LoPublished in: ACS applied materials & interfaces (2017)
We demonstrate a nanotechnology approach for the development of cancer-cell-specific subcellular organelle-targeted drug nanocarriers based on photostable nanodiamonds (ND) functionalized with folic acid and mitochondrial localizing sequence (MLS) peptides. We showed that these multifunctional NDs not only distinguish between cancer cells and normal cells, and transport the loaded drugs across the plasma membrane of cancer cells, but also selectively deliver them to mitochondria and induce significant cytotoxicity and cell death compared with free Dox localized in lysosomes. Importantly, the cellular uptake of Dox was dramatically increased in a resistant model of MCF-7 cells, which contributed to the significant circumvention of P-glycoprotein-mediated drug resistance. Our work provides a novel method of designing nanodiamond-based carriers for targeted delivery and for circumventing drug resistance in doxorubicin-resistant human breast adenocarcinoma cancer cells.
Keyphrases
- drug delivery
- cancer therapy
- cell death
- cell cycle arrest
- induced apoptosis
- drug release
- squamous cell carcinoma
- oxidative stress
- endothelial cells
- quantum dots
- emergency department
- reactive oxygen species
- pi k akt
- signaling pathway
- locally advanced
- cell proliferation
- mass spectrometry
- breast cancer cells
- radiation therapy