title: Overcoming multidrug resistance of cancer cells by direct intranuclear drug delivery using TAT-conjugated mesoporous silica nanoparticles.
abstract: The development of multidrug resistance (MDR) in cancer cells is one of major obstacles to the effective cancer chemotherapy. In this report we demonstrate the effective circumvention of multidrug resistance in cancer cells by an active nuclear-targeted drug delivery system that was constructed by conjugating TAT peptide onto the surface of mesoporous silica nanoparticles (MSNs-TAT). The conjugation of TAT peptide facilitated the intranuclear localization of MSNs-TAT and the release of the encapsulated drugs directly within the nucleoplasm. The direct intranuclear drug delivery of doxorubicin (DOX) in multidrug resistant MCF-7/ADR cancer cells was capable of increasing the intracellular as well as intranuclear drug concentrations much more effectively than free DOX or delivered by MSNs in the absence of TAT peptide. With the nuclear drug delivery fashion, DOX-MSNs-TAT presents a promising strategy in overcoming MDR in cancer cells and improving the therapeutic index of currently available chemotherapeutics by enhancing therapeutic efficacy and reducing side effects.
authors: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.
authors: Limin
authors: L
authors: Pan
authors: Jianan
authors: J
authors: Liu
authors: Qianjun
authors: Q
authors: He
authors: Lijun
authors: L
authors: Wang
authors: Jianlin
authors: J
authors: Shi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D012822:Silicon Dioxide; D004317:Doxorubicin