abstract
- Nanoscaled drug carriers have been developed to accumulate in tumors and release a drug cargo either passively or in response to a local stimulus. However, strategies that rely on passive release or response to a local stimulus do not allow for spatial and temporal control of drug delivery. These limitations motivate interest in drug delivery platforms that release cargo in response to an external stimulus. This contribution describes magnetically controlled nanocarriers (MCNCs) that release heat and a drug cargo in response to an applied alternating magnetic field (AMF). The MCNCs consist of a hydrophobic core of superparamagnetic iron oxide nanoparticles that release heat in response to an AMF and a thermoresponsive polymer that releases a molecular cargo via breakage of thermally labile Diels–Alder (DA) bonds. The nanocarriers are coated with polyethylene glycol-block-polylactic acid (PEG4.9kD-PLA6.0kD) block copolymer to confer colloidal stability and water solubility. The MCNCs are assembled through flash nanoprecipitation, a rapid approach to making nanoparticles that is scalable and provides control of size and composition. Release experiments show that application of an AMF results in on-demand heat and drug release. The AMF-actuated release ceases when the field is turned off, and multiple applications of AMF result in programmable release. The amount of release is tunable via the AMF field strength and can be spatially controlled using selection magnetic field gradients. These results suggest that a potent combination of magnetic hyperthermia and drug release can be actuated in a desired region.