for various fields, such as drug delivery, [1,2] biosensing, [3] detoxification, [4] and environmental remediation. [5] These miniaturized machines can convert local fuel or external energy (e.g., magnetic, ultrasound, or light) to driving force and obtain selfpropulsion in dynamic surroundings. [6] Due to the increasing demands and rigorous requirements of biomedical community, the composition of microrobots has been evolving from rigid and inorganic materials to functional and endogenous cells. [7] Incorporating natural cells with synthetic micromachines creates an elegant platform with synergistic properties of cell biofunctionalities and effective propulsion. The cargo-loading capability of cells is employed by cell-based microrobots to actively deliver drugs, [2,[8][9][10][11] such as red blood cell (RBC)based micromotors loaded with doxorubicin (DOX) and photosensitizer, [10,11] and neutrophil-based microrobots carrying paclitaxel (PTX). [2] However, the utilized chemotherapeutic agents in the robotic system are not specific to cancerous cells and occur drug leakage during transport, inducing unavoidable toxicity to normal regions along with limited therapeutic efficacy and undesired side effects. [12] Such compromised biosafety and antitumor index hinder the practical A unique robotic medical platform is designed by utilizing cell robots as the active "Trojan horse" of oncolytic adenovirus (OA), capable of tumor-selective binding and killing. The OA-loaded cell robots are fabricated by entirely modifying OA-infected 293T cells with cyclic arginine-glycine-aspartic acid tripeptide (cRGD) to specifically bind with bladder cancer cells, followed by asymmetric immobilization of Fe 3 O 4 nanoparticles (NPs) on the cell surface. OA can replicate in host cells and induce cytolysis to release the virus progeny to the surrounding tumor sites for sustainable infection and oncolysis. The asymmetric coating of magnetic NPs bestows the cell robots with effective movement in various media and wireless manipulation with directional migration in a microfluidic device and bladder mold under magnetic control, further enabling steerable movement and prolonged retention of cell robots in the mouse bladder. The biorecognition of cRGD and robust, controllable propulsion of cell robots work synergistically to greatly enhance their tissue penetration and anticancer efficacy in the 3D cancer spheroid and orthotopic mouse bladder tumor model. Overall, this study integrates cell-based microrobots with virotherapy to generate an attractive robotic system with tumor specificity, expanding the operation scope of cell robots in biomedical community.
Cell robots that transform natural cells into active platforms hold great potential to enrich the biomedical prospects of artificial microrobots. Here, we present Janus yeast cell microrobots (JYC-robots) prepared by asymmetrically coating Fe3O4 nanoparticles (NPs) and subsequent in situ growth of zeolitic imidazolate framework-67 (ZIF-67) on the surface of yeast cells. The magnetic actuation relies on the Fe3O4 NPs wrapping. As the compositions of cell robots, the cell wall with abundant polysaccharide coupling with porous and oxidative ZIF-67 can concurrently remove mycotoxin (e.g., zearalenone (ZEN)). The magnetic propulsion accelerates the decontamination efficiency of JYC-robots against ZEN. Although yeast cells with fully coating of Fe3O4 NPs and ZIF-67 (FC-yeasts) show faster movement than JYC-robots, higher toxin-removal efficacy is observed for JYC-robots compared with that of FC-yeasts, reflecting the vital factor of the yeast cell wall in removing mycotoxin. Such design with Janus modification of magnetic NPs (MNPs) and entire coating of ZIF-67 generates active cell robot platform capable of fuel-free propulsion and enhanced detoxification, offering a new formation to develop cell-based robotics system for environmental remediation.
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