Nanoparticles (NPs) have emerged as an advantageous drug delivery platform for the treatment of various ailments including cancer and cardiovascular and inflammatory diseases. However, their efficacy in shuttling materials to diseased tissue is hampered by a number of physiological barriers. One hurdle is transport out of the blood vessels, compounded by difficulties in subsequent penetration into the target tissue. Here, we report the use of two distinct micropropellers powered by rotating magnetic fields to increase diffusion-limited NP transport by enhancing local fluid convection. In the first approach, we used a single synthetic magnetic microrobot called an artificial bacterial flagellum (ABF), and in the second approach, we used swarms of magnetotactic bacteria (MTB) to create a directable “living ferrofluid” by exploiting ferrohydrodynamics. Both approaches enhance NP transport in a microfluidic model of blood extravasation and tissue penetration that consists of microchannels bordered by a collagen matrix.
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.
Wireless‐manipulated graphite coated nanomagnets are promising candidates for minimally invasive targeted drug delivery platforms. Iron nanowires coated with graphitic shells are synthesized by template‐assisted deposition. The use of porous aluminum oxide templates enables both the batch production of nanowires by electrodeposition and their subsequent conformal encapsulation in graphite using chemical vapor deposition (CVD). High quality graphitic shells are obtained when CVD conditions are optimized using acetylene as carbon feedstock at 740 °C. Interestingly, the iron nanowires transform into iron carbide during the CVD process leading to changes in magnetic properties. The graphite coated iron nanowires are precisely manipulated against a water flow (0.1 mm/s) using a magnetic field of 350 Oe and a gradient of 50 kOe m−1 in a 5‐DOF magnetic manipulation system. Our approach opens new avenues for the design and synthesis of functional graphite coated nanowires that are promising for nanorobotics applications.
Hybrid magnetic phospholipidic-based tubular and helical microagents are wirelessly manipulated by means of a 5-DOF electromagnetic system. Two different strategies are used to manipulate these nanostructures in simulated biologic capillaries. Tubules are pulled by applying magnetic field gradients and oriented by magnetic fields. Helices exhibit a cork-screw motion similar to the swimming strategy used by motile bacteria such as E. coli.
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