Canagliflozin-loaded magnetic nanoparticles as potential treatment of hypoxic tumors in combination with radiotherapy

What is it about?

Hypoxia (lack of oxygen) develops in solid tumors and plays an essential role in tumor progression and recurrence, since hypoxic cells can resist to chemo- and radio-therapy. Hypoxic tumor cells are particularly sensitive to glucose supply. This work demonstrates the design of canagliflozin-loaded magnetic nanoparticles as potential treatment of difficult to treat hypoxic tumors in combination with radiotherapy. Canagliflozin (CANA) is a sodium-glucose transport protein inhibitor (SGLT2-inhibitor) used today for diabetes type II treatment. The magnetic nanoparticles were made from iron oxide coated with poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate) (PMAA-g-PEGMA) copolymer and CANA was covalently coupled to these nanoparticles by hydrolysable in the body ester bonds. In a mouset cancer model, the combination of CANA-loaded nanoparticles with radiotherapy (in the presence of an external magnetic field at the tumor site to collect the particles in tumor) was the most efficient treatment in delaying tumor growth, exhibiting higher antitumor activity compared to the combination of free CANA with radiotherapy. The work shows for the first time the significant anticancer potential of a more selective delivery to tumors of SGLT2 inhibitors in combination with radiotherapy.

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