Material concept and design has undergone significant advancement in the biomedical field in order to achieve desired structures, properties, and functionalities 1. Recently, nature-inspired design-strategies have been adopted by various interdisciplinary research groups to develop smart and sustainable devices for medical and healthcare applications2,3,4. Microrobots (micro/nano-sized robots) are one such invention that are inspired by micro-organism such as bacteria, motor proteins and spermatozoa etc. to perform various biomedical tasks 5. Microrobots (MRs) are highly desirable because of their relatively large size which allows them to be more readily visualized under a microscope compared to nano-size robots 6. These MRs can be driven by various chemical (H2O2, H2O and NaBH4) and external energy fields (magnetic field, UV, ultrasound) through narrow and confined spaces with precise control7. Particularly, magnetic MRs are of great interest due to their ability to be actuated under the influence of a magnetic field allowing for the use of a custom-designed workspace with various motion control methods 8. Magnetically actuated MRs can be steered to different inaccessible parts of the body without resorting to invasive procedures. Moreover, diverse structural and surface properties of magnetic MRs offer potential uses in the field of delivery systems, tracking, and single cell manipulation 8, 9.
In a living organism, every single activity is a function of all the biochemical reactions that happen at a cellular level. These biochemical reactions are often a collection of all the synchronized processes that are carried out at a subcellular level inside the cells 10. Any alteration in these highly specialized pathways can corrupt specific or multiple biological signals which often lead to disease onset 11. Cancer is the simplest example of a dysfunctional mechanism inside a cell that causes uncontrolled growth of the cells 12. Birth defects are another example where abnormalities in a single cell lead to impaired development of the fetus 13. Furthermore, correlations between abrupt changes in intracellular electric current across the cell and cardiac arrhythmia are also evident from previous research 14. Likewise, dysfunctional cellular mechanisms are the apparent cause of neurodegenerative diseases and diabetes as well 15,16. Therefore, targeting these subcellular pathways or microstructures have been important in drug discovery and development 17.
Recent reports have demonstrated that the application of a low frequency magnetic field (LFMF) effectively inhibits cancer cell proliferation and triggers apoptosis 18. Different magnetic particles like magnetic disks, iron microparticles, carbon nanotubes and magnetized-silica spindle-shaped particles were used to generate low-frequency magnetic field that kills cancer cells (magnetolysis) 19,20,21,22. While LFMF is known to inhibit cell proliferation and induce apoptosis by metabolic shift and affecting gene expression, respectively, 23,24 these reports have reported different mechanisms of cell death either by direct cell membrane damage or mechanical stress-induced apoptosis 22,25. Although these studies have demonstrated the magnetolysis effect of magnetic particles on cancer cells in different experimental set up, effect of the LFMF and the mechanism of cell death at a single cell level is yet to be determined. The use of microrobots for such an application has also not been realized despite the additional positioning and targeting control that can be obtained.
In this present study, we use magnetically oscillating microrobots to induce cell lysis. The MRs were internalized by the cells, which does not result in toxic effects. Cancer cells with internalized MRs were then aligned in the direction of magnetic fields and oscillated via fast rotating magnetic fields in the xy plane. These results show that magnetic microrobots can be used as an effective means to kill cancer cells by a straightforward application of an alternating magnetic field.