www.advhealthmat.de FULL PAPER 1900213 (1 of 11) © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Magnetically Actuated Degradable Microrobots for Actively Controlled Drug Release and Hyperthermia Therapy Jongeon Park, Chaewon Jin, Seungmin Lee, Jin-Young Kim,* and Hongsoo Choi* DOI: 10.1002/adhm.201900213 Orally or intravenously administered drugs circulate and affect not only the target area but also normal cells or tis- sues. This can lead to adverse drug reac- tions and increases the dose required for efficacy. [5] These problems can be over- come by using magnetically actuated microrobots for targeted therapy. [1b,6] Magnetic 3D microrobots and micro/ nanoparticles controlled by an external magnetic actuation system (EMAS) have been used for drug or cell delivery. [1b,d,g,h,i,2] However, most studies conducted loading and delivery of drugs (or cells) examina- tions but did not perform quantitative analysis, such as the drug-loading capacity and drug release profile over time, which are fundamental aspects of the use of microrobots for targeted drug delivery. Cancer treatment could be enhanced by induction of targeted hyperthermia in addition to drug delivery. [7] Studies of hyperthermia using magnetic nanoparticles (MNPs) and an AMF have been performed. [3] However, MNPs have a low driving force in a microfluidic environment due to their size and spherical shape and the high viscosity of the fluid. [8] In addition, activated MNPs may veer off-course during navigation to a target area. [8a,9] This would hamper control of the drug dose and heat energy delivered to the target area. After introduction of a drug, homeostasis may not be possible due to physiolog- ical elimination or degradation by the liver or kidney. [10] In this case, the drug concentration may fluctuate outside of the thera- peutic window, decreasing efficacy. [11] Therefore, there is a need to actively control the amount of drug released from the micro- robots, to provide an efficacious drug concentration in response to changes in the therapeutic requirements. In addition to locomotion and drug delivery, it is also important to retrieve microrobots after use. This would be nullified by use of a degradable material. Such biodegrad- able microrobots are degraded in aqueous solutions with no harmful byproduct. [12] Microrobots composed of various biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA), and poly(ethylene glycol) diacrylate (PEGDA) have been developed. [12c,13] For use in vivo, biostealth materials are necessary to protect microrobots from the immune system, [14] e.g., poly(ethylene glycol) (PEG). [15] PEGDA, which has PEG functionality, is suitable for microrobots due to its biodegrada- bility, biostealth, and ease of fabrication. [13a,16] Magnetic carriers have not to date been used for 3D degradable microrobots for targeted drug delivery and hyperthermia therapy. Microrobots facilitate targeted therapy due to their small size, minimal inva- siveness, and precise wireless control. A degradable hyperthermia microrobot (DHM) with a 3D helical structure is developed, enabling actively controlled drug delivery, release, and hyperthermia therapy. The microrobot is made of poly(ethylene glycol) diacrylate (PEGDA) and pentaerythritol triacrylate (PETA) and contains magnetic Fe 3 O 4 nanoparticles (MNPs) and 5-fluorouracil (5-FU). Its locomotion is remotely and precisely controlled by a rotating magnetic field (RMF) generated by an electromagnetic actuation system. Drug-free DHMs reduce the viability of cancer cells by elevating the temperature under an alternating magnetic field (AMF), a hyperthermic effect. 5-FU is released from the proposed DHMs in normal-, high-burst-, and constant-release modes, controlled by the AMF. Finally, actively controlled drug release from the DHMs in normal- and high-burst-release mode results in a reduction in cell viability. The reduction in cell viability is of greater magnitude in high- burst- than in normal-release mode. In summary, biodegradable DHMs have potential for actively controlled drug release and hyperthermia therapy. J. E. Park, C. W. Jin, S. M. Lee, Dr. J.-Y. Kim, Prof. H. S. Choi Department of Robotics Engineering DGIST-ETH Microrobot Research Center Daegu Gyeongbuk Institute of Science and Technology (DGIST) 333, Techno jungang-daero, Hyeonpung-Myeon, Dalseong-Gun, Daegu 42988, Republic of Korea E-mail: jy.kim@dgist.ac.kr; mems@dgist.ac.kr The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adhm.201900213. Microrobots 1. Introduction Microrobots show promise for biomedical applications, such as minimally invasive surgery and targeted therapy, due to their small size, minimal invasiveness, and precise wireless control. [1] Miniaturized microrobots require an efficient actua- tion strategy to propel them because there is no room for a power supply or battery. A magnetic field is suitable for this purpose because it can penetrate biological tissue without damage. [2] Magnetic field energy can be converted to kinetic energy by magnetic objects under a magnetic field gradient or a rotating magnetic field (RMF), or into thermal energy under an alternating magnetic field (AMF). [3] The former allows remote and precise navigation of magnetic objects along a controlled trajectory, and the latter localized heating. [3c] These benefits make microrobots ideal for targeted therapy, which has fewer side effects and greater efficacy than conventional therapies. [4] Adv. Healthcare Mater. 2019, 1900213