Molecular cargo delivery using multicellular magnetic microswimmers

Abstract The recent emergence of versatile micro/nanorobots provides new strategies of healthcare and disease treatment, especially for targeted delivery of therapeutic agents to otherwise inaccessible regions. However, for successful translation of laboratory microrobotic tools into clinical outcomes, critical challenges still remain, such as controllable cargo loading/release on site, robust spatiotemporal navigation in real time and reliable biocompatibility/biodegradation inside the body. Herein, we report the loading, transport and release of molecular cargos using cell-based magnetic microswimmers engineered from multicellular Spirulina. The loading is attained by harnessing the dehydration and rehydration of Spirulina cells, inside which model macromolecules are encapsulated as a discrete phase, and for small molecules, as a continuous phase. Driven by low-strength magnetic fields, the molecule-laden swimmer manages to perform navigation in an intestinal tract mimicry, imitating the process of guest-molecule transport in the gastrointestinal tract. The loaded molecules can be released from the swimmer through host degradation and/or concentration gradient-driven diffusion, with the speed of release tailored by the magnetite-coating thickness. Furthermore, evaluation tests in a stem-cell system infer that the bioactivity of the guest molecules remains intact after the loading-release procedure. In summary, we have demonstrated a feasible approach for gastrointestinal delivery of molecular agents using cell-based microswimmers.