A smart hyperthermia nanofi ber is described with simultaneous heat generation and drug release in response to 'on-off ' switching of alternating magnetic fi eld (AMF) for induction of skin cancer apoptosis. The nanofi ber is composed of a chemically-crosslinkable temperature-responsive polymer with an anticancer drug (doxorubicin; DOX) and magnetic nanoparticles (MNPs), which serve as a trigger of drug release and a source of heat, respectively. By chemical crosslinking, the nanofi ber mesh shows switchable changes in the swelling ratio in response to alternating 'on-off ' switches of AMF because the self-generated heat from the incorporated MNPs induces the deswelling of polymer networks in the nanofi ber. Correspondingly, the 'on-off ' release of DOX from the nanofi bers is observed in response to AMF. The 70% of human melanoma cells died in only 5 min application of AMF in the presence of the MNPs and DOX incorporated nanofi bers by double effects of heat and drug. Taken together these advantages on both the nano-and macroscopic scale of nanofi bers demonstrate that the dynamically and reversibly tunable structures have the potential to be utilized as a manipulative hyperthermia material as well as a switchable drug release platform by simple switching an AMF 'on' and 'off '.

In this study, specific interactions between immobilized RGDS (Arg-Gly-Asp-Ser) cell adhesion peptides and cell integrin receptors located on cell membranes are controlled in vitro using stimuli-responsive polymer surface chemistry. Temperature-responsive poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide) (P(IPAAm-co-CIPAAm)) copolymer grafted onto tissue culture grade polystyrene (TCPS) dishes permits RGDS immobilization. These surfaces facilitate the spreading of human umbilical vein endothelial cells (HUVECs) without serum depending on RGDS surface content at 37 degrees C (above the lower critical solution temperature, LCST, of the copolymer). Moreover, cells spread on RGDS-immobilized surfaces at 37 degrees C detach spontaneously by lowering culture temperature below the LCST as hydrated grafted copolymer chains dissociate immobilized RGDS from cell integrins. These cell lifting behaviors upon hydration are similar to results using soluble RGDS in culture as a competitive substitution for immobilized ligands. Binding of cell integrins to immobilized RGDS on cell culture substrates can be reversed spontaneously using mild environmental stimulation, such as temperature, without enzymatic or chemical treatment. These findings are important for control of specific interactions between proteins and cells, and subsequent "on-off" regulation of their function. Furthermore, the method allows serum-free cell culture and trypsin-free cell harvest, essentially removing mammalian-sourced components from the culture process.

Shape-memory surfaces with on-demand, tunable nanopatterns are developed to observe time dependent changes in cell alignment using temperature-responsive poly(ϵ-caprolactone) (PCL) films. Temporary grooved nanopatterns are easily programmed on the films and triggered to transition quickly to permanent surface patterns by the application of body heat. A time-dependent cytoskeleton remodeling is also observed under biologically relevant conditions.

A stimuli-responsive magnetic nanoparticle system for diagnostic target capture and concentration has been developed for microfluidic lab card settings. Telechelic poly(N-isopropylacrylamide) (PNIPAAm) polymer chains were synthesized with dodecyl tails at one end and a reactive carboxylate at the opposite end by the reversible addition fragmentation transfer technique. These PNIPAAm chains self-associate into nanoscale micelles that were used as dimensional confinements to synthesize the magnetic nanoparticles. The resulting superparamagnetic nanoparticles exhibit a gamma-Fe2O3 core ( approximately 5 nm) with a layer of carboxylate-terminated PNIPAAm chains as a corona on the surface. The carboxylate group was used to functionalize the magnetic nanoparticles with biotin and subsequently with streptavidin. The functionalized magnetic nanoparticles can be reversibly aggregated in solution as the temperature is cycled through the PNIPAAm lower critical solution temperature (LCST). While the magnetophoretic mobility of the individual nanoparticles below the LCST is negligible, the aggregates formed above the LCST are large enough to respond to an applied magnetic field. The magnetic nanoparticles can associate with biotinylated targets as individual particles, and then subsequent application of a combined temperature increase and magnetic field can be used to magnetically separate the aggregated particles onto the poly(ethylene glycol)-modified polydimethylsiloxane channel walls of a microfluidic device. When the magnetic field is turned off and the temperature is reversed, the captured aggregates redisperse into the channel flow stream for further downstream processing. The dual magnetic- and temperature-responsive nanoparticles can thus be used as soluble reagents to capture diagnostic targets at a controlled time point and channel position. They can then be isolated and released after the nanoparticles have captured target molecules, overcoming the problem of low magnetophoretic mobility of the individual particle while retaining the advantages of a high surface to volume ratio and faster diffusive properties during target capture.