Abstract
This study aimed to evaluate whether magnetic core-shell polymersome combining ascorbic acid with iron oxide nanoparticles can serves as a magnetic field responsive theranostics platform for MRI-guided ferroptosis mediated cancer treatment. Magnetic polymersome composed by ascorbic acid (AA) and iron oxide nanoparticles in the PLGA polymersome. An alternating magnetic field (2Hz)-triggered-release of ascorbic acid from the core of magnetic polymersome and following the ferric/ferrous reduction of iron oxide nanoparticles embedded in the shell region and following MRI signal changes were tested. In vitro assays we observed the magnetic field triggered ferroptosis mediated cell death in HepG2 cells. Finally, in vivo feasibility of MRI-guided ferroptosis mediated cancer treatment were evaluated in both mice bearing HepG2 and McA-RH7777 rat HCC tumor models. TEM images confirmed the core-shell structure of magnetic polymersome and magnetic field induced structural deformation. UV-vis spectrum showed the magnetic field triggered AA release and following the reduction of the ferric (Fe3+) in the iron oxide nanoparticles to ferrous (Fe2+). In vitro assay found that the significant increasement of reactive oxygen species (ROS) level in HepG2 cells and significantly enhanced ferroptosis mediated cancer cells death. In vitro MRI T2 signal changes at pre/post magnetic field application confirmed the ratio changes of ferric and ferrous. In vivo studies verify that magnetic field triggered MRI T2 contrast changes and ferroptosis mediated tumor growth inhibition after the local infusion of magnetic polymersome in both HepG2 mouse (I.T.) and McA RH-7777 HCC rat model (I.A.). Our demonstrated magnetic field triggered MRI T2 signal changes and following ferroptosis mediated cancer cell killing effects using magnetic core-shell polymersome will be a promising approach for interventioinal MR image-guided cancer therapies.
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