An implantable smart hyperthermia nanofiber with switchable, controlled and sustained drug release: Possible application in prevention of cancer local recurrence

Temperature-responsive drug-loaded electrospun nanofibers have gained huge critical attention as efficient localized implantable devices in preventing cancer local recurrence. In this regard, a smart hyperthermia nanofiber with the simultaneous heat-generation and dual-stage drug release ability in response to ‘ON-OFF’ switching of an alternating magnetic field (AMF) for improved hyperthermic chemotherapy has been developed. The smart hyperthermia nanofibrous scaffolds are fabricated via electrospinning a temperature-responsive copolymer blended with iron oxide (II, III) magnetic nanoparticles (MNPs, 10 nm), metformin (MET), and mesoporous silica nanoparticles (MSNs) loaded with MET (MSNs@MET). It was found that all the magnetic nanofibers (MNFs) possess heat generation property and ‘ON-OFF’ switchable heating ability. The swelling ratio with reversible alterations and the corresponding drug discharge in response to AMF application with ‘ON-OFF’ switching was also demonstrated. MET-MNFs showed an initial rapid discharge in the 1st cycle of AMF application while MET released from MET@MSNs-MNFs exhibited a sustained release without the initial rapid discharge. It was found that MET-MET@MSNs-MNFs displayed a blend of initial rapid discharge and late prolonged drug discharge. In a magnetic field for 300 s during the second and third days, the metabolic activity of B16F10 skin melanoma cells incubated with all types of MNFs was decreased. Importantly, MET-MET@MSNs-MNFs had enhanced cytotoxicity than the MET-MNFs and MET@MSNs-MNFs (P < .05), due to the double effects of heat and dual-stage drug release. These results demonstrated that the proposed two-stage drug discharge approach plus hyperthermia is more desirable to standard chemotherapy regimens and might effectively induce cytotoxicity via a synergistic effect over a relatively long time.