title: Doxorubicin-tethered fluorescent silica nanoparticles for pH-responsive anticancer drug delivery.
abstract: The therapeutic potential of doxorubicin hydrochloride (DOX), an anticancer drug, is limited by its dose-related side effects and non-selective delivery to healthy and cancerous cells. Here we show a drug delivery system based on doxorubicin-tethered fluorescent silica nanoparticles (DOX-Hyd@FSiNPs). The DOX was conjugated to the FSiNPs through a hydrazone linkage. After uptake into the acidic environment of cancer cells, DOX was released from the FSiNPs' surfaces because of the breakage of the pH-sensitive hydrazine bond. The decreased viability of cells in the HeLa cancer cell line indicates that DOX-Hyd@FSiNPs are potential candidates for cancer therapy. Nuclear staining and Z-axis scanning with confocal laser scanning microscopy demonstrated that DOX-Hyd@FSiNPs were effectively delivered into the cytoplasm of HeLa cells; the released DOX accumulating in the nucleus. The fluorescence of the FSiNPs also allowed the live-tracking of the nanoparticles in the cell.
authors.affiliation: Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China. Electronic address: jlkong@fudan.edu.cn.
authors.forename: Jilie
authors.initials: J
authors.lastname: Kong
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D004705:Endocytosis; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D005453:Fluorescence; D006367:HeLa Cells; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D006834:Hydrazines; C029424:hydrazine; D012822:Silicon Dioxide; D004317:Doxorubicin; D016650:Fluorescein-5-isothiocyanate
keywords: Cancer therapy; Doxorubicin; Drug delivery; Fluorescent silica nanoparticle; Hydrazone