title: Cancer-Cell-Specific Mitochondria-Targeted Drug Delivery by Dual-Ligand-Functionalized Nanodiamonds Circumvent Drug Resistance.
abstract: 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.
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong , Kowloon Tong, Hong Kong SAR.
authors.forename: Miu Shan
authors.initials: MS
authors.lastname: Chan
authors.affiliation: Key Laboratory of Biochip Technology, Biotech and Health Care, Shenzhen Research Institute of City University of Hong Kong , Shenzhen 518057, China.
authors.forename: Ling Sum
authors.initials: LS
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biochip Technology, Biotech and Health Care, Shenzhen Research Institute of City University of Hong Kong , Shenzhen 518057, China.
authors.forename: Hoi Man
authors.initials: HM
authors.lastname: Leung
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong , Kowloon Tong, Hong Kong SAR.
authors.forename: Pik Kwan
authors.identifier: http://orcid.org/0000-0001-5255-1718
authors.initials: PK
authors.lastname: Lo
mesh_terms: D045744:Cell Line, Tumor; D004317:Doxorubicin; D004337:Drug Carriers; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D006801:Humans; D061986:MCF-7 Cells; D008928:Mitochondria; D058612:Nanodiamonds
chemical_list: D004337:Drug Carriers; D058612:Nanodiamonds; D004317:Doxorubicin
keywords: drug resistance; mitochondria; nanodiamonds; peptides; targeted delivery