Ferrofluids Based on Anionic Polysaccharide-Coated Magnetic Nanoparticles for Targeted Magnetocatalytic-Driven Multimodal Anticancer Therapy

Regrettably, glioblastoma multiforme (GBM) remains the deadliest form of brain cancer, with a very unfavorable prognosis for life expectancy for the patient. We report, for the first time, the green colloidal synthesis of cobalt-doped magnetic iron oxide nanoparticles (Co-MNPs) as aqueous ferrofluids, using two anionic polysaccharide biopolymers, hyaluronic acid (HA) and carboxymethyl cellulose (CMC), as surfactants. These ferrofluids based on magnetite nanoparticles (HA@Co-MNP and CMC@Co-MNP) demonstrated superparamagnetic properties and magnetic-to-thermal conversion upon exposure to an alternating magnetic field (AMF), with the extent of conversion dependent on surfactant type. In addition, the ferrophase acted as a nanozyme, mimicking peroxidase-like activity in response to hydrogen peroxide, which is present at higher levels in tumor cells. The coupling of magnetic-heat capabilities with biocatalytic behavior enhances glioblastoma cell elimination and suppresses 3D neurospheroid growth. The results also showed that active targeting based on the HA biopolymer shell, due to its affinity for CD44 membrane receptors overexpressed in GBM, outperformed CMC-coated ferrofluid analogs. These magnetocatalytic-responsive nanoplatforms offer a broad avenue for the diagnosis and therapy of numerous cancers, potentially improving patients’ quality of life and prognoses.