Magnetically Actuated Helical Microrobot with Magnetic Nanoparticle Retrieval and Sequential Dual-Drug Release Abilities

Cancer is one of the diseases with high mortality worldwide.Variousmethods for cancer treatment are being developed, and among them,magnetically driven microrobots capable of minimally invasive surgeryand accurate targeting are in the spotlight. However, existing medicalmagnetically manipulated microrobots contain magnetic nanoparticles(MNPs), which can cause toxicity to normal cells after the deliveryof therapeutic drugs. In addition, there is a limitation in that cancercells become resistant to the drug by mainly delivering only one drug,thereby reducing the treatment efficiency. In this paper, to overcomethese limitations, we propose a microrobot that can separate/retrieveMNPs after precise targeting of the microrobot and can sequentiallydeliver dual drugs (gemcitabine (GEM) and doxorubicin (DOX)). First,after the proposed microrobot targeting, MNPs attached to the microrobotsurface can be separated from the microrobot using focused ultrasound(FUS) and retrieved through an external magnetic field. Second, theactive release of the first conjugated drug GEM to the surface ofthe microrobot is possible using near-infrared (NIR), and as the microrobotslowly decomposes over time, the release of the second encapsulatedDOX is possible. Therefore, it is possible to increase the cancercell treatment efficiency with sequential dual drugs in the microrobot.We performed basic experiments on the targeting of the proposed magneticallymanipulated microrobot, separation/retrieval of MNPs, and the sequentialdual-drug release and validated the performances of the microrobotthrough in vitro experiments using the EMA/FUS/NIRintegrated system. As a result, the proposed microrobot is expectedto be used as one of the methods to improve cancer cell treatmentefficiency by improving the limitations of existing microrobots incancer cell treatment.