Chitosan/Alginate Polyelectrolyte Magnetic Gel Nanoarchitectonics with Tunable Mechanical Properties for Magnetic Hyperthermia and Sustained Release of 5-Fluorouracil

Chitosan-based hydrogels hold promise as drug delivery systems for cancer therapy, but the poor mechanical properties often limit the biological application, requiring chemical cross-linking to improve sustained drug release. Besides, the addition of stimulus-responsiveness to chitosan requires chemical modifications that can further affect the gel properties. To overcome these challenges, in this work, a novel chitosan/alginate polyelectrolyte magnetic gel with tunable mechanical properties is developed by pH-triggered self-assembly. The gels could be prepared by a slow/fast pH decrease and blended with magnetic nanoparticles. Manganese-doped ferrite nanoparticles (∼10 nm) with suitable magnetic properties (>70 Am²/kg) and high magnetic hyperthermia heating efficiency (ILP > 3 nHm²/kg) were synthesized via an amino acid-assisted oxidative hydrothermal method. The nanoparticles and self-assembly conditions of the polyelectrolyte complex enabled the tuning of the gels' properties, a fast gelation, and suitable mechanical properties for drug delivery. Notably, gels with a large storage modulus (up to 10 kPa) could be prepared at a low polymer concentration (≤2 wt %). The magnetic gels enabled the sustained release of a hydrophilic chemotherapeutic drug model, 5-fluorouracil (5-FU), under mimetic physiological conditions, outperforming the hydrogels. Moreover, the drug release kinetics was synergistically enhanced under the combined effect of acidic conditions and magnetic hyperthermia. Hence, the developed self-assembled chitosan/alginate magnetic gel showed promising multifunctionality, combining tunable mechanical properties, magnetic hyperthermia capability, and sustained drug release. These features highlight the self-assembled chitosan/alginate magnetic gels as promising and versatile materials for localized and controlled drug delivery.