Elucidating the mechanism of cellular uptake and
Magnetic NPs (m NPs), such as superparamagnetic iron oxide nanoparticles (Fe), are of such a size that they are easily magnetised under an applied field, but lose their magnetism as soon as the magnetic field is removed (thus preventing NP aggregation), and provide an excellent platform for use in clinic.Currently m NPs are employed in clinic in MRI, which allows intra-tissue and intracellular detection.imaging and improved treatment of disease, with the ultimate aim of producing a more theranostic approach.Due to their small sizes, the nanoparticles can cross most of the biological barriers such as the blood vessels and the blood brain barrier, thus providing ubiquitous access to most tissues.Clathrin- medicated endocytosis appeared to be responsible for uptake as shown PCR and western blot, with Pitstop 2 (known to selectively block clathrin formation) blocking particle uptake.Interestingly, it was further shown that a magnetic field was able to reverse or overcome the blocking, suggesting an alternative route of uptake.Although the mechanism of action of biguanides remains imperfectly understood the efficacy of metformin in the treatment of type 2 diabetes is unchallenged.Metformin was developed based on the natural product galegine.
[email protected] [email protected] and Center for Research at Bio/Nano Interface, Department of Chemistry and Department of Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and Mc Knight Brain Institute, University of Florida, Gainesville, Florida 32611-7200, USA.
This study sheds also light on biguanides anti-cancer properties.
A better understanding of biguanides mechanism of action could lead to improved outcomes for millions of diabetics worldwide as well as it could provide a new protein target for the treatment of cancer.
The assumption that the effects of metformin are exclusively mediated by AMPK has recently been challenged by genetic loss-of-function experiments.
Since then it has been hypothesized that metformin inhibits hepatic gluconeogenesis by interfering with the c AMP/PKA pathway acting as a glucagon antagonist.