Cationic Surface Modification Combined with Collagen Enhances the Stability and Delivery of Magnetosomes for Tumor Hyperthermia

Magnetosomes (MTS), membrane-enclosed magnetic nanoparticles naturally biomineralized by magnetotactic bacteria, are promising materials for tumor hyperthermia owing to their good biocompatibility and heating efficiency. However, their application is limited by poor suspension stability and low injectability at high concentrations. This study aimed to enhance magnetosome stability and delivery performance through surface cationization combined with collagen matrix stabilization. The resulting cationic magnetosomes (CMTS) exhibited an increased positive charge on the outer membrane. Collagen, functioning as a negatively charged matrix under mildly alkaline conditions, effectively stabilized the cationic magnetosomes, forming CMTS-collagen aqueous suspensions (CMTS-Colas) that remained well-suspended for over 24 h and could be easily resuspended after 10 days of storage. Compared with native magnetosome suspensions, CMTS in collagen displayed smaller hydrodynamic diameters and significantly improved injectability through 26G and 31G fine needles. Under an alternating magnetic field, 2 mg/mL CMTS-Colas efficiently induced over 98% apoptosis in hepatoma cells after two treatment sessions and led to complete loss of cell viability after three sessions. These findings demonstrate that CMTS-Colas substantially improve the suspension stability and injectability of magnetosomes while maintaining strong hyperthermic efficacy, suggesting a promising strategy for stabilizing magnetosomes and potentially benefiting other charged, aggregation-prone magnetic biomaterials.