Publication Highlights
Due to the difficulty of targeting systemically delivered therapeutics for cancer, interest has grown in exploiting biological agents to enhance tumor accumulation and mediate localized drug delivery. Equipped with onboard sensing and active motility, some cells respond to specific cues of the tumor microenvironment, making them ideal candidates for smart cancer therapy. Herein, recent progress and developments are presented on the use of four of the most promising cell-based systems for tumor targeting and drug delivery—immune cells, stem cells, platelets, and bacteria. Strategies to further enhance specificity at the tissue and cell level are discussed, including genetic engineering, chemical cell surface modification, and the use of external physical stimuli. With crucial ongoing efforts addressing the safety and efficacy of living intelligent therapeutics, a new era of cancer medicine is on the horizon.
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Biohybrid bacteria-based microrobots are increasingly recognized as promising externally controllable vehicles for targeted cancer therapy. Magnetic fields in particular have been used as a safe means to transfer energy and direct their motion. Thus far, the magnetic control strategies used in this context rely on poorly scalable magnetic field gradients, require active position feedback, or are ill-suited to diffuse distributions within the body. Here, we present a magnetic torque-driven control scheme for enhanced transport through biological barriers that complements the innate taxis toward tumor cores exhibited by a range of bacteria, shown for Magnetospirillum magneticum as a magnetically responsive model organism. This hybrid control strategy is readily scalable, independent of position feedback, and applicable to bacterial microrobots dispersed by the circulatory system. We observed a fourfold increase in translocation of magnetically responsive bacteria across a model of the vascular endothelium and found that the primary mechanism driving increased transport is torque-driven surface exploration at the cell interface. Using spheroids as a three-dimensional tumor model, fluorescently labeled bacteria colonized their core regions with up to 21-fold higher signal in samples exposed to rotating magnetic fields. In addition to enhanced transport, we demonstrated that our control scheme offers further advantages, including the possibility for closed-loop optimization based on inductive detection, as well as spatially selective actuation to reduce off-target effects. Last, after systemic intravenous injection in mice, we showed significantly increased bacterial tumor accumulation, supporting the feasibility of deploying this control scheme clinically for magnetically responsive biohybrid microrobots.
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