Magnetically controlled diatom-based microrobots for targeted drug delivery and combined chemo-photodynamic treatment of glioblastoma

The potential of micro-nano robots in biomedical applications, especially targeted drug delivery, has drawn much attention. Despite substantial advancements, challenges remain in achieving precise control and effective drug release at target locations. Here, we developed a magnetic biohybrid microrobot using diatom frustules for drug delivery, named Mag-Frustules. Their movement was controlled by a rotating magnetic field, and they exhibited the ability to move against the flow. Deep learning algorithms and adaptive fuzzy PID control were employed to achieve closed-loop control and autonomous movement along a preset trajectory. The drug-loading capability was further optimized through vacuum loading, and drug release was triggered by ultrasonication. In vitro experiments showed that DOX-loaded Mag-Frustules reduced U87 glioblastoma cell viability, while the combined use of DOX-loaded and THPP-loaded Mag-Frustules produced a stronger inhibitory effect than either single-treatment group. Furthermore, magnetic guidance increased the local accumulation of drug-loaded Mag-Frustules at the target site. These results demonstrate a GBM-oriented Mag-Frustule platform that integrates closed-loop magnetic navigation, motion in a microfluidic flow environment, vacuum-enhanced drug loading, ultrasonication-assisted drug release, magnetic enrichment, and chemo-photodynamic combined treatment, providing a potential active-delivery strategy for glioblastoma-related applications.