Inorganic nanovehicle targets tumor in an orthotopic breast cancer model
| Autor: | Chae-Ok Yun, Jin-Ho Choy, Oh-Joon Kwon, Goeun Choi, Yeon-Ji Oh |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
musculoskeletal diseases
Biodistribution Antimetabolites Antineoplastic Magnesium Hydroxide Drug Compounding Apoptosis Breast Neoplasms Drug resistance Pharmacology Article Mice Mammary Glands Animal immune system diseases Cell Line Tumor medicine Distribution (pharmacology) Animals Humans heterocyclic compounds Annexin A5 Particle Size skin and connective tissue diseases Cell Proliferation Drug Carriers Multidisciplinary Chemistry Tumor Burden Methotrexate Liver Drug delivery Cancer cell Heterografts Aluminum Silicates Female Drug carrier Neoplasm Transplantation medicine.drug Half-Life Propidium |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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