Radiofrequency-Triggered Drug Release from Nanoliposomes with Millimeter-Scale Resolution Using a Superimposed Static...

Drug delivery to a specific site in the body typically relies on the use of targeting agents that recognize a unique biomarker. Unfortunately, it is often difficult to identify unique molecular signatures that exist only at the site of interest. An alternative strategy is to deliver energy (e.g., light) to locally trigger release from a drug carrier; however, the use of this approach is limited because energy delivery to deep tissues is often impractical or invasive. In this work, radiofrequency-responsive superparamagnetic iron oxide nanoparticles (SPIONs) are used to trigger drug release from nanoscale vesicles. Because the body is inherently nonmagnetic, this approach allows for deep tissue targeting. To overcome the unfavorable meter-scale diffraction limit of SPION-compatible radiofrequency (RF) fields, a strong static gating field containing a sharp zero point is superimposed on the RF field. Only drug carriers that are at or near the zero point are susceptible to RF-triggered drug release, thereby localizing drug delivery with millimeter-scale resolution. This approach induces >40% drug release from thermally responsive doxorubicin-loaded liposomes within a 3.2 mm radius of the zero point with <10% release in the surrounding area, leading to a >2.5 therapeutic index in Huh 7 hepatocellular carcinoma cells.