Oxygen depleted hypoxic regions in the tumour are generally resistant to therapies1. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour2 of magnetotactic bacteria3, Magnetococcus marinus strain MC-14, can be used to transport drug-loaded nanoliposomes into hypoxic regions of the tumour. In their natural environment, MC-1 cells, each containing a chain of magnetic iron-oxide nanocrystals5, tend to swim along local magnetic field lines and towards low oxygen concentrations6 based on a two-state aerotactic sensing system2. We show that when MC-1 cells bearing covalently bound drug-containing nanoliposomes were injected near the tumour in SCID Beige mice and magnetically guided, up to 55% of MC-1 cells penetrated into hypoxic regions of HCT116 colorectal xenografts. Approximately 70 drug-loaded nanoliposomes were attached to each MC-1 cell. Our results suggest that harnessing swarms of microorganisms exhibiting magneto-aerotactic behaviour can significantly improve the therapeutic index of various nanocarriers in tumour hypoxic regions.

Actuation is essential for artificial machines to interact with their surrounding environment and to accomplish the functions for which they are designed. Over the past few decades, there has been considerable progress in developing new actuation technologies. However, controlled motion still represents a considerable bottleneck for many applications and hampers the development of advanced robots, especially at small length scales. Nature has solved this problem using molecular motors that, through living cells, are assembled into multiscale ensembles with integrated control systems. These systems can scale force production from piconewtons up to kilonewtons. By leveraging the performance of living cells and tissues and directly interfacing them with artificial components, it should be possible to exploit the intricacy and metabolic efficiency of biological actuation within artificial machines. We provide a survey of important advances in this biohybrid actuation paradigm.

Although nanorobots may play critical roles for many applications in the human body such as targeting tumoral lesions for therapeutic purposes, miniaturization of the power source with an effective onboard controllable propulsion and steering system have prevented the implementation of such mobile robots. Here, we show that the flagellated nanomotors combined with the nanometersized magnetosomes of a single Magnetotactic Bacterium (MTB) can be used as an effective integrated propulsion and steering system for devices such as nanorobots designed for targeting locations only accessible through the smallest capillaries in humans while being visible for tracking and monitoring purposes using modern medical imaging modalities such as Magnetic Resonance Imaging (MRI). Through directional and magnetic field intensities, the displacement speeds, directions, and behaviors of swarms of these bacterial actuators can be controlled from an external computer.

A proposed framework for regulatory, ethical, and legal discussions identifies six levels of autonomy for medical robotics.

The feasibility for in vivo navigation of untethered devices or robots is demonstrated with the control and tracking of a 1.5 mm diameter ferromagnetic bead in the carotid artery of a living swine using a clinical magnetic resonance imaging ͑MRI͒ platform. Navigation is achieved by inducing displacement forces from the three orthogonal slice selection and signal encoding gradient coils of a standard MRI system. The proposed method performs automatic tracking, propulsion, and computer control sequences at a sufficient rate to allow navigation along preplanned paths in the blood circulatory system. This technique expands the range of applications in MRI-based interventions.

Bacterial actuation and manipulation are demonstrated where Magnetospirillum gryphiswaldense magnetotactic bacteria ͑MTB͒ are used to push 3 m beads at an average velocity of 7.5 m s −1 along preplanned paths by modifying the torque on a chain of magnetosomes in the bacterium with a directional magnetic field of at least 0.5 G generated from a small programmed electrical current. But measured average thrusts of 0.5 and 4 pN of the flagellar motor of a single Magnetospirillum gryphiswaldense and MC-1 MTB suggest that average velocities greater than 16 and 128 m s −1 , respectively could be achieved.The behaviors of bacteria in low Reynolds number hydrodynamics 1 suggest that they could be used to manipulate efficiently suspended micro-objects in fluids for potential applications in microsystems such as lab-on-a-chip and Micro-Total-Analysis Systems. Here, electro-osmosis 2 or dielectrophoresis 3 based on the principle of electrokinetics is used where frequencies and voltage amplitudes dependent on dielectric properties are required to induce a force. Our method referred here to as bacterial manipulation is independent of the dielectric properties and may prove to be suitable for many applications when low electrical power and compactness are required.The integration of bacteria as functional components has been previously done, 4,5 where Serratia marcescens flagellated bacteria were attached to polydimethylsiloxane or polystyrene to form a bacterial carpet for moving fluid. Until then, bacteria were operating without external control appropriate for manipulation of micro-objects. Typical bacteria swims according to the so-called run-and-tumble pattern that can be explained by chemotaxis 6 models while remaining unpredictable for micromanipulation. We show here that magnetotactic bacteria ͑MTB͒ are more appropriate to carry out computer-based controlled micromanipulation or microactuation of micro-objects.The exploitation of the motility of MTB has been done in the past such as in low field orientation magnetic separation 7 being a process, where motile, magnetic field susceptible MTB can be separated. Micromanipulation of MTB using microelectromagnets arrays has also been described. 8,9 In all these previous examples, MTB were the entities being manipulated instead of being used to manipulate other objects as described here.Each MTB ͑Ref. 10͒ possesses a chain of magnetosomes which are membrane-based nanoparticles of a magnetic iron. Because of this chain, the swimming direction of MTB although influenced by chemotaxis and aerotaxis is mainly based on magnetotaxis, 11-13 being more "compatible" with electronics and computer-based software platforms. Al-though several types of MTB exist and can be found all over the world, in this study, Magnetospirillum gryphiswaldense bacteria 14 were used. This MTB has a length of ϳ1-3 m with a swimming speed of ϳ40-80 m / s. Magnetotaxis as chemotaxis 15-17 also influences the motility of MTB in search of nutrient gradients. To modify the paths of the MTB, magnetic field lines ...

Medical nanorobotics exploits nanometer-scale components and phenomena with robotics to provide new medical diagnostic and interventional tools. Here, the architecture and main specifications of a novel medical interventional platform based on nanorobotics and nanomedicine, and suited to target regions inaccessible to catheterization are described. The robotic platform uses magnetic resonance imaging (MRI) for feeding back information to a controller responsible for the real-time control and navigation along pre-planned paths in the blood vessels of untethered magnetic carriers, nanorobots, and/or magnetotactic bacteria (MTB) loaded with sensory or therapeutic agents acting like a wireless robotic arm, manipulator, or other extensions necessary to perform specific remote tasks. Unlike known magnetic targeting methods, the present platform allows us to reach locations deep in the human body while enhancing targeting efficacy using real-time navigational or trajectory control. The paper describes several versions of the platform upgraded through additional software and hardware modules allowing enhanced targeting efficacy and operations in very difficult locations such as tumoral lesions only accessible through complex microvasculature networks.

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