Catalase-Powered Nanobots for Overcoming the Mucus Barrier.

Biological barriers present a significant obstacle to treatment, especially when drugs are administered locally to increase their concentrations at the target site while minimizing unintended off-target effects. Among these barriers, mucus presents a challenge, as it serves as a protective layer in the respiratory, urogenital, and gastrointestinal tracts. Its role is to shield the underlying epithelial cells from pathogens and toxic compounds but also impedes the efficient delivery of drugs. Despite the exploration of mucolytic agents to improve drug delivery, overcoming this protective barrier remains a significant hurdle. In our study, we investigate an alternative approach involving the use of catalase-powered nanobots. We use an in vitro model that simulates intestinal mucus secretion to demonstrate the dual functionality of our nanobots. This includes their ability to disrupt mucus, which we confirmed through in vitro and ex vivo validation, as well as their self-propulsion to overcome the mucus barrier, resulting in a 60-fold increase compared with passive nanoparticles. Therefore, our findings highlight the potential utility of catalase-powered nanobots as carriers for therapeutic agents since they could enhance drug delivery efficiency by penetrating the mucus barrier.

Boosting the Efficiency of Photoactive Rod-Shaped Nanomotors via Magnetic Field-Induced Charge Separation.

Photocatalytic nanomotors have attracted a lot of attention because of their unique capacity to simultaneously convert light and chemical energy into mechanical motion with a fast photoresponse. Recent discoveries demonstrate that the integration of optical and magnetic components within a single nanomotor platform offers novel advantages for precise motion control and enhanced photocatalytic performance. Despite these advancements, the impact of magnetic fields on energy transfer dynamics in photocatalytic nanomotors remains unexplored. Here, we introduce dual-responsive rod-like nanomotors, made of a TiO2/NiFe heterojunction, able to (i) self-propel upon irradiation, (ii) align with the direction of an external magnetic field, and (iii) exhibit enhanced photocatalytic performance. Consequently, when combining light irradiation with a homogeneous magnetic field, these nanomotors exhibit increased velocities attributed to their improved photoactivity. As a proof-of-concept, we investigated the ability of these nanomotors to generate phenol, a valuable chemical feedstock, from benzene under combined optical and magnetic fields. Remarkably, the application of an external magnetic field led to a 100% increase in the photocatalytic phenol generation in comparison with light activation alone. By using various state-of-the-art techniques such as photoelectrochemistry, electrochemical impedance spectroscopy, photoluminescence, and electron paramagnetic resonance, we characterized the charge transfer between the semiconductor and the alloy component, revealing that the magnetic field significantly improved charge pair separation and enhanced hydroxyl radical generation. Consequently, our work provides valuable insights into the role of magnetic fields in the mechanisms of light-driven photocatalytic nanomotors for designing more effective light-driven nanodevices for selective oxidations.

Integrable Magnetic Fluid Hyperthermia Systems for 3D Magnetic Particle Imaging.

Background: Combining magnetic particle imaging (MPI) and magnetic fluid hyperthermia (MFH) offers the ability to perform localized hyperthermia and magnetic particle imaging-assisted thermometry of hyperthermia treatment. This allows precise regional selective heating inside the body without invasive interventions. In current MPI-MFH platforms, separate systems are used, which require object transfer from one system to another. Here, we present the design, development and evaluation process for integrable MFH platforms, which extends a commercial MPI scanner with the functionality of MFH. Methods: The biggest issue of integrating magnetic fluid hyperthermia platforms into a magnetic particle imaging system is the magnetic coupling of the devices, which induces high voltage in the imaging system, and is harming its components. In this paper, we use a self-compensation approach derived from heuristic algorithms to protect the magnetic particle imaging scanner. The integrable platforms are evaluated regarding electrical and magnetic characteristics, cooling capability, field strength, the magnetic coupling to a replica of the magnetic particle imaging system's main solenoid and particle heating. Results: The MFH platforms generate suitable magnetic fields for the magnetic heating of particles and are compatible with a commercial magnetic particle imaging scanner. In combination with the imaging system, selective heating with a gradient field and steerable heating positioning using the MPI focus fields are possible. Conclusion: The proposed MFH platforms serve as a therapeutic tool to unlock the MFH functionality of a commercial magnetic particle imaging scanner, enabling its use in future preclinical trials of MPI-guided, spatially selective magnetic hyperthermia therapy.

Swarms of Enzyme-Powered Nanomotors Enhance the Diffusion of Macromolecules in Viscous Media.

Over the past decades, the development of nanoparticles (NPs) to increase the efficiency of clinical treatments has been subject of intense research. Yet, most NPs have been reported to possess low efficacy as their actuation is hindered by biological barriers. For instance, synovial fluid (SF) present in the joints is mainly composed of hyaluronic acid (HA). These viscous media pose a challenge for many applications in nanomedicine, as passive NPs tend to become trapped in complex networks, which reduces their ability to reach the target location. This problem can be addressed by using active NPs (nanomotors, NMs) that are self-propelled by enzymatic reactions, although the development of enzyme-powered NMs, capable of navigating these viscous environments, remains a considerable challenge. Here, the synergistic effects of two NMs troops, namely hyaluronidase NMs (HyaNMs, Troop 1) and urease NMs (UrNMs, Troop 2) are demonstrated. Troop 1 interacts with the SF by reducing its viscosity, thus allowing Troop 2 to swim more easily through the SF. Through their collective motion, Troop 2 increases the diffusion of macromolecules. These results pave the way for more widespread use of enzyme-powered NMs, e.g., for treating joint injuries and improving therapeutic effectiveness compared with traditional methods.

Light-Triggered Mechanical Disruption of Extracellular Barriers by Swarms of Enzyme-Powered Nanomotors for Enhanced Delivery.

Targeted drug delivery depends on the ability of nanocarriers to reach the target site, which requires the penetration of different biological barriers. Penetration is usually low and slow because of passive diffusion and steric hindrance. Nanomotors (NMs) have been suggested as the next generation of nanocarriers in drug delivery due to their autonomous motion and associated mixing hydrodynamics, especially when acting collectively as a swarm. Here, we explore the concept of enzyme-powered NMs designed as such that they can exert disruptive mechanical forces upon laser irradiation. The urease-powered motion and swarm behavior improve translational movement compared to passive diffusion of state-of-the-art nanocarriers, while optically triggered vapor nanobubbles can destroy biological barriers and reduce steric hindrance. We show that these motors, named Swarm 1, collectively displace through a microchannel blocked with type 1 collagen protein fibers (barrier model), accumulate onto the fibers, and disrupt them completely upon laser irradiation. We evaluate the disruption of the microenvironment induced by these NMs (Swarm 1) by quantifying the efficiency by which a second type of fluorescent NMs (Swarm 2) can move through the cleared microchannel and be taken up by HeLa cells at the other side of the channel. Experiments showed that the delivery efficiency of Swarm 2 NMs in a clean path was increased 12-fold in the presence of urea as fuel compared to when no fuel was added. When the path was blocked with the collagen fibers, delivery efficiency dropped considerably and only depicted a 10-fold enhancement after pretreatment of the collagen-filled channel with Swarm 1 NMs and laser irradiation. The synergistic effect of active motion (chemically propelled) and mechanical disruption (light-triggered nanobubbles) of a biological barrier represents a clear advantage for the improvement of therapies which currently fail due to inadequate passage of drug delivery carriers through biological barriers.

Navigation of a magnetic micro-robot through a cerebral aneurysm phantom with magnetic particle imaging.

Cerebral aneurysms are potentially life threatening and nowadays treated by a catheter-guided coiling or by a neurosurgical clipping intervention. Here, we propose a helically shaped magnetic micro-robot, which can be steered by magnetic fields in an untethered manner and could be applied for a novel coiling procedure. This is shown by navigating the micro-robot through an additively manufactured phantom of a human cerebral aneurysm. The magnetic fields are applied with a magnetic particle imaging (MPI) scanner, which allows for the navigation and tomographic visualization by the same machine. With MPI the actuation process can be visualized with a localization accuracy of 0.68 mm and an angiogram can be acquired both without any radiation exposure. First in-vitro phantom experiments are presented, showing an idea of a robot conducted treatment of cerebral aneurysms.

Evaluation of antiplasmodial activity and cytotoxicity assays of amino acids functionalized magnetite nanoparticles: Hyperthermia and flow cytometry applications.

We report the synthesis of magnetite nanoparticles (MNP) and their functionalization with glycine (MNPGly), ß-alanine (MNPAla), L-phenylalanine (MNPPhAla), D-(-)-α-phenylglycine (MNPPhGly) amino acids. The functionalized nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), electron paramagnetic resonance (EPR), vibrating sample magnetometry (VSM), Mössbauer spectroscopy (MS), magnetic hyperthermia (MH), dynamic light scattering and zeta potential. The functionalized nanoparticles had isoelectric points (IEP) at pH ≃ 4.4, 5.8, 5.9 and 6.8 for samples MNPGly, MNPAla, MNPPhGly and MNPPhAla, respectively, while pure magnetite had an IEP at pH 5.6. In the MH experiments, the samples showed specific absorption rate (SAR) of 64, 71, 74, 81 and 66 W/g for MNP, MNPGly, MNPAla, MNPPhGly, and MNPPhAla, respectively. We used a flow cytometric technique to determine the cellular magnetic nanoparticles plus amino acids content. Magnetic fractionation and characterization of Resovist® magnetic nanoparticles were performed for applications in magnetic particle imaging (MPI). We have also studied the antiproliferative and antiparasitic effects of functionalized MNPs. Overall, the data showed that the functionalized nanoparticles have great potential for using as environmental, antitumor, antiparasitic agents and clinical applications.

Dosimetry in magnetic fields with dedicated MR-compatible ionization chambers.

MR-integrated radiotherapy requires suitable dosimetry detectors to be used in magnetic fields. This study investigates the feasibility of using dedicated MR-compatible ionization chambers at MR-integrated radiotherapy devices. MR-compatible ionization chambers (Exradin A19MR, A1SLMR, A26MR, A28MR) were precisely modeled and their relative response in a 6MV treatment beam in the presence of a magnetic field was simulated using EGSnrc. Monte Carlo simulations were carried out with the magnetic field in three orientations: the magnetic field aligned perpendicular to the chamber and beam axis (transverse orientation), the magnetic field parallel to the chamber as well as parallel to the beam axis. Monte Carlo simulation results were validated with measurements using an electromagnet with magnetic field strength upto 1.1 T with the chambers in transverse orientation. The measurements and simulation results were in good agreement, except for the A26MR ionization chamber in transverse orientation. The maximum increase in response of the ionization chambers observed was 8.6% for the transverse orientation. No appreciable change in chamber response due to the magnetic field was observed for the magnetic field parallel to the ionization chamber and parallel to the photon beam. Polarity and recombination correction factor were experimentally investigated in the transverse orientation. The polarity effect and recombination effect were not altered by a magnetic field. This study further investigates the response of the ionization chambers as a function of the chambers' rotation around their longitudinal axis. A variation in response was observed when the chamber was not rotationally symmetric, which was independent of the magnetic field.

Magnetic particle imaging in vascular medicine.

Magnetic particle imaging (MPI) is a new medical imaging technique that enables three-dimensional real-time imaging of a magnetic tracer material. Although it is not yet in clinical use, it is highly promising, especially for vascular and interventional imaging. The advantages of MPI are that no ionizing radiation is necessary, its high sensitivity enables the detection of very small amounts of the tracer material, and its high temporal resolution enables real-time imaging, which makes MPI suitable as an interventional imaging technique. As MPI is a tracer-based imaging technique, functional imaging is possible by attaching specific molecules to the tracer material. In the first part of this article, the basic principle of MPI will be explained and a short overview of the principles of the generation and spatial encoding of the tracer signal will be given. After this, the used tracer materials as well as their behavior in MPI will be introduced. A subsequent presentation of selected scanner topologies will show the current state of research and the limitations researchers are facing on the way from preclinical toward human-sized scanners. Furthermore, it will be briefly shown how to reconstruct an image from the tracer materials' signal. In the last part, a variety of possible future clinical applications will be presented with an emphasis on vascular imaging, such as the use of MPI during cardiovascular interventions by visualizing the instruments. Investigations will be discussed, which show the feasibility to quantify the degree of stenosis and diagnose strokes and traumatic brain injuries as well as cerebral or gastrointestinal bleeding with MPI. As MPI is not only suitable for vascular medicine but also offers a broad range of other possible applications, a selection of those will be briefly presented at the end of the article.