Magnetically Triggered Drug-Release System and Magnetic Caged Calcium Using Iron Oxide Nanoparticles and Hydrogels

Abstract

Magnetic field-responsive materials have been utilized as drug carriers that release payload drugs under a magnetic field, allowing precise spatiotemporal control of drug release. These materials also have potential as chemical tools that can regulate signal transduction in deep regions of the body. However, they have typically been specialized either as drug carriers or as chemical tools. To address these challenges, we developed here a versatile alternating magnetic field (AMF)-responsive platform consisting of polymer-coated iron oxide nanoparticles (PCIOs) and thermoresponsive hydrogels based on poly(N-isopropylacrylamide) (PNIPAM). We demonstrated that PCIOs could increase the medium temperature from 22 to 45 °C within 5 min under an AMF of 16 mT and 386 kHz, resulting in the release of the neutral drug model PM-546 from the PNIPAM-based hydrogel under physiological conditions. The combination system was further utilized as a chemical tool for controlling extracellular calcium ions (Ca²⁺), which are crucial for membrane potential regulation, bone resorption, cytokine induction, and intestinal homeostasis. The chemical tool, termed magnetic caged calcium, was constructed by replacing the drug carrier gel with a thermoresponsive Ca²⁺-binding gel based on PNIPAM coated by poly(methacrylic acid). This gel reversibly adsorbed Ca²⁺ in a submillimolar range as the temperature increased from 25 to 45 °C. The magnetic caged calcium significantly decreased [Ca²⁺] by 0.18 ± 0.06 mM under the AMF exposure for 1 h. These results indicate that the PCIO–hydrogel combination serves as a foundation for AMF-induced drug-release systems operating under physiological conditions and for magnetic caged systems regulating extracellular calcium, leading to broad applications in both medical applications and fundamental studies of signal transduction in deep tissues in the future.