Immunomodulation and delivery of macrophages using nano-smooth drug-loaded magnetic microrobots for dual targeting cancer therapy

To realize the potential to use micro/nanorobots for targeted cancer therapy, it is important to improve their biocompatibility and targeting ability. Here, we report on drug-loaded magnetic microrobots capable of polarizing macrophages into the antitumor phenotype to target and inhibit cancer cells. In vitro tests demonstrated that the microrobots have good biocompatibility with normal cells and immune cells. Positively charged DOX was loaded onto the surface of microrobots via electrostatic interactions and exhibited pH-responsive release behavior. The nano-smooth surfaces of the microrobots activated M1 polarization of macrophages, thus activating their intrinsic targeting and antitumor abilities toward cancer cells. Through dual targeting from magnetic guidance and M1 macrophages, the microrobots were able to target and kill cancer cells in a 3D tumor spheroid culture assay. These findings demonstrate a way to improve the tumor-targeting and antitumor abilities of microrobots through the combined use of magnetic control, macrophages, and pH-responsive drug release.