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: Goeun Choi, Oh-Joon Kwon, Yeonji Oh, Chae-Ok Yun, Jin-Ho Choy
• Journal: Scientific reports (Sci Rep) Vol. 4 Pg. 4430 (Mar 21 2014) ISSN: 2045-2322 [Electronic] England
• PMID: 24651154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aluminum Silicates
• Annexin A5
• Antimetabolites, Antineoplastic
• Drug Carriers
• Propidium
• Magnesium Hydroxide
• Methotrexate

Topics

• Aluminum Silicates (chemistry)
• Animals
• Annexin A5
• Antimetabolites, Antineoplastic (chemistry, pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Carriers
• Drug Compounding
• Female
• Half-Life
• Heterografts
• Humans
• Liver (drug effects)
• Magnesium Hydroxide (chemistry)
• Mammary Glands, Animal (drug effects, pathology)
• Methotrexate (chemistry, pharmacology)
• Mice
• Neoplasm Transplantation
• Particle Size
• Propidium
• Tumor Burden (drug effects)