For drug delivery in cancer therapy, various stimuli-responsive hydrogel-based micro-devices have been studied with great interest. Here, we present a new concept for a hybrid actuated soft microrobot targeted drug delivery. The proposed soft microrobot consists of a hydrogel bilayer structure of 2-hydroxyethyl methacrylate (PHEMA) and poly (ethylene glycol) acrylate (PEGDA) with iron (II, III) oxide particles (Fe ₃ O ₄ ). The PHEMA layer as a pH-responsive gel is used for a trapping and unfolding motion of the soft microrobot in pH-varying solution, and the PEGDA-with-Fe ₃ O ₄ layer is employed for the locomotion of the soft microrobot in the magnetic field. The bilayer soft microrobot was fabricated by a conventional photolithography procedure and its characteristics were analyzed and presented. To evaluate the trapping performance and the motility of the soft microrobot, test solutions with different pH values and an electromagnetic actuation (EMA) system were used. First, the soft microrobot showed its full trapping motion at about pH 9.58 and its unfolding motion at about pH 2.6. Second, the soft microrobot showed a moving velocity of about 600 μ m s ⁻¹ through the generated magnetic field of the EMA system. Finally, we fabricated the real anti-cancer drug microbeads (PCL-DTX) and executed the cytotoxicity test using the mammary carcinoma cells (4T1). The viability of the 4T1 cells treated with the proposed microrobot and the PCL-DTX microbeads decreased to 70.25 ± 1.52%. The result demonstrated that the soft microrobot can be moved to a target position by the EMA system and can release a small amount of beads by the pH variation and the robot exhibited no toxicity to the cells. In the future, we expect that the proposed soft microrobot can be applied to a new tumor-therapeutic tool that can move to a target tumor and release anti-tumor drugs.

A human stem cell–based microrobot system for knee cartilage regeneration was designed with consideration of clinical trials.

We propose a bacteria-based microrobot (bacteriobot) based on a new fusion paradigm for theranostic activities against solid tumors. We develop a bacteriobot using the strong attachment of bacteria to Cy5.5-coated polystyrene microbeads due to the high-affinity interaction between biotin and streptavidin. The chemotactic responses of the bacteria and the bacteriobots to the concentration gradients of lysates or spheroids of solid tumors can be detected as the migration of the bacteria and/or the bacteriobots out of the central region toward the side regions in a chemotactic microfluidic chamber. The bacteriobots showed higher migration velocity toward tumor cell lysates or spheroids than toward normal cells. In addition, when only the bacteriobots were injected to the CT-26 tumor mouse model, Cy5.5 signal was detected from the tumor site of the mouse model. In-vitro and in-vivo tests verified that the bacteriobots had chemotactic motility and tumor targeting ability. The new microrobot paradigm in which bacteria act as microactuators and microsensors to deliver microstructures to tumors can be considered a new theranostic methodology for targeting and treating solid tumors.

Microrobots that can be precisely guided to target lesions have been studied for in vivo medical applications. However, existing microrobots have challenges in vivo such as biocompatibility, biodegradability, actuation module, and intra- and postoperative imaging. This study reports microrobots visualized with real-time x-ray and magnetic resonance imaging (MRI) that can be magnetically guided to tumor feeding vessels for transcatheter liver chemoembolization in vivo. The microrobots, composed of a hydrogel-enveloped porous structure and magnetic nanoparticles, enable targeted delivery of therapeutic and imaging agents via magnetic guidance from the actuation module under real-time x-ray imaging. In addition, the microrobots can be tracked using MRI as postoperative imaging and then slowly degrade over time. The in vivo validation of microrobot system–mediated chemoembolization was demonstrated in a rat liver with a tumor model. The proposed microrobot provides an advanced medical robotic platform that can overcome the limitations of existing microrobots and current liver chemoembolization.

Using macrophage recruitment in tumors, we develop active, transportable, cancer theragnostic macrophage-based microrobots as vector to deliver therapeutic agents to tumor regions. The macrophage-based microrobots contain docetaxel (DTX)-loaded poly-lactic-co-glycolic-acid (PLGA) nanoparticles (NPs) for chemotherapy and Fe₃O₄ magnetic NPs (MNPs) for active targeting using an electromagnetic actuation (EMA) system. And, the macrophage-based microrobots are synthesized through the phagocytosis of the drug NPs and MNPs in the macrophages. The anticancer effects of the microrobots on tumor cell lines (CT-26 and 4T1) are evaluated in vitro by cytotoxic assay. In addition, the active tumor targeting by the EMA system and macrophage recruitment, and the chemotherapeutic effect of the microrobots are evaluated using three-dimensional (3D) tumor spheroids. The microrobots exhibited clear cytotoxicity toward tumor cells, with a low survivability rate (<50%). The 3D tumor spheroid assay showed that the microrobots demonstrated hybrid actuation through active tumor targeting by the EMA system and infiltration into the tumor spheroid by macrophage recruitment, resulting in tumor cell death caused by the delivered antitumor drug. Thus, the active, transportable, macrophage-based theragnostic microrobots can be considered to be biocompatible vectors for cancer therapy.