Development of Magnetic Nanofibrous Membranes for Localized Solid Cancer Treatment ^†

The present work focuses on the development of dual-stimuli electrospun fibers embedded with thermoresponsive PNIPAAm microgels and iron oxide magnetic nanoparticles for a synergic effect between magnetic hyperthermia and controlled drug release as an alternative localized cancer treatment for solid tumors. Superparamagnetic iron oxide nanoparticles were successfully synthesized using a chemical co-precipitation technique and stabilized with oleic acid (OA) and dimercaptosuccinic acid (DMSA). Thermoresponsive PNIPAAm microgels with a lower critical solution temperature of 32 °C were synthesized through surfactant-free emulsion polymerization [1,2,3]. Poly(vinyl alcohol) (PVA) was used as a fiber template, and a fiber diameter of about 180 nm was obtained. PNIPAAm microgels and mNPs were incorporated into the nanofibers through colloidal electrospinning, and dual-stimuli nanofibrous membranes were produced. To avoid their dissolution in an aqueous medium, the membranes were submitted to physical crosslinking. Stress tests confirm that the crosslinking of the membranes increases their mechanical parameters and that the presence of microgels and nanoparticles acts as a reinforcement in the fibers. The swelling ability of the membranes is shown to decrease in the composite membranes when compared with plain PVA membranes due to the presence of magnetic nanoparticles. Magnetic hyperthermia assays show promising results regarding the heating ability of the magnetic membranes incorporated into the fibers. PVA fibers incorporated with DMSA-coated nanoparticles were capable of reaching therapeutic temperatures for hyperthermia treatment, indicating that the device is a viable option in cancer treatment. In drug-release assays, PVA fibers with a model drug, doxorubicin (DOX), were produced, and controlled release was studied in different pH solutions (4.5, 6.5, and 7.4) at 37 °C. Assays showed a more significant release of DOX at pH = 7.4. Finally, to evaluate the cytotoxic effect of the device, cytotoxicity assays of PNIPAAm microgels and PVA fibers were performed in Vero and SaOs-2 cells. All assays reveal the absence of cytotoxicity, indicating the possibility of using the device in biomedical applications. A dual-stimuli electrospun device was successfully developed, and the present work demonstrates its potential for magnetic hyperthermia and controlled drug release that shows potential as an alternative cancer treatment.