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.

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.

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.

The targeted and effective delivery of therapeutic agents remains an unmet goal in the field of controlled release systems. Magnetococcus marinus MC-1 magnetotactic bacteria (MTB) are investigated as potential therapeutic carriers. By combining directional magnetotaxis-microaerophilic control of these self-propelled agents, a larger amount of therapeutics can be delivered surpassing the diffusion limits of large drug molecules toward hard-to-treat hypoxic regions in solid tumors. The potential benefits of these carriers emphasize the need to develop an adequate method to attach therapeutic cargos, such as drug-loaded nanoliposomes, without substantially affecting the cell's ability to act as delivery agents. In this study, we report on a strategy for the attachment of liposomes to MTB (MTB-LP) through carbodiimide chemistry. The attachment efficacy, motility, and magnetic response of the MTB-LP were investigated. Results confirm that a substantial number of nanoliposomes (∼70) are efficiently linked with MTB without compromising functionality and motility. Cytotoxicity assays using three different cell types (J774, NIH/3T3, and Colo205) reveal that liposomal attachments to MTB formulation improve the biocompatibility of MTB, whereas attachment does not interfere with liposomal uptake.

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Magnetotactic bacteria (MTB) can be viewed as self-propelled natural microrobots. These bacterial microrobots can be remotely controlled using magnetic fields due to their internal chain of iron-oxide nanoparticles acting like a compass needle. This internal chain enables them to adopt a magnetotactic behavior that can be exploited to perform a variety of microscale tasks from microassembly and micro-manufacturing to the delivery through microvascular networks of therapeutic agents to tumors. To effectively support these applications, three-dimensional (3D) aggregations of MTB become essential in order to manipulate and guide the bacteria effectively in the human microvasculature to deliver a predefined dose of therapeutics. To achieve such aggregations in a 3D volume, time-varying magnetic field sequences were developed enabling us to simulate in time the existence of a magnetic monopole. This article presents and compares three different time-varying magnetic field sequences generated by three orthogonal pairs of electromagnets able to generate such 3D aggregations of MTB.