title: Daunorubicin-TiO2 nanocomposites as a "smart" pH-responsive drug delivery system.
abstract: Daunorubicin (DNR) has a broad spectrum of anticancer activity, but is limited in clinical application due to its serious side effects. The aim of this study was to explore a novel "smart" pH-responsive drug delivery system (DDS) based on titanium dioxide (TiO(2)) nanoparticles for its potential in enabling more intelligent controlled release and enhancing chemotherapeutic efficiency of DNR. DNR was loaded onto TiO(2) nanoparticles by forming complexes with transition metal titanium to construct DNR-TiO(2) nanocomposites as a DDS. DNR was released from the DDS much more rapidly at pH 5.0 and 6.0 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. DNR-TiO(2) nanocomposites induced remarkable improvement in anticancer activity, as demonstrated by flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and nuclear 4',6-diamidino- 2-phenylindole staining. Furthermore, the possible signaling pathway was explored by western blot. For instance, in human leukemia K562 cells, it was demonstrated that DNR-TiO(2) nanocomposites increase intracellular concentration of DNR and enhance its anticancer efficiency by inducing apoptosis in a caspase-dependent manner, indicating that DNR-TiO(2) nanocomposites could act as an efficient DDS importing DNR into target cancer cells. These findings suggest that "smart" DNR delivery strategy is a promising approach to cancer therapy.
authors.affiliation: Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
authors.forename: Cailian
authors.initials: C
authors.lastname: Wang
authors.forename: Baoan
authors.initials: B
authors.lastname: Chen
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020014:K562 Cells; D053761:Nanocomposites / Q000737:chemistry*; D014025:Titanium / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; C009495:titanium dioxide; D014025:Titanium; D053148:Caspase 3; D003630:Daunorubicin