title: Inorganic nanovehicle targets tumor in an orthotopic breast cancer model.
abstract: The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.
authors.affiliation: Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science (Ewha Global Top 5 program-2011) and Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Goeun
authors.initials: G
authors.lastname: Choi
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Oh-Joon
authors.initials: OJ
authors.lastname: Kwon
authors.affiliation: Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science (Ewha Global Top 5 program-2011) and Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Yeonji
authors.initials: Y
authors.lastname: Oh
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
authors.affiliation: Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science (Ewha Global Top 5 program-2011) and Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choy
mesh_terms: D000538:Aluminum Silicates / Q000737:chemistry*; D000818:Animals; D017304:Annexin A5; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D006207:Half-Life; D064593:Heterografts; D006801:Humans; D008099:Liver / Q000187:drug effects; D008276:Magnesium Hydroxide / Q000737:chemistry*; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000473:pathology; D008727:Methotrexate / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D009368:Neoplasm Transplantation; D010316:Particle Size; D011419:Propidium; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000538:Aluminum Silicates; D017304:Annexin A5; D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D011419:Propidium; D008276:Magnesium Hydroxide; D008727:Methotrexate