Delivering drugs with microrobots Nelson, Bradley J; Pané, Salvador
Science (American Association for the Advancement of Science),
12/2023, Letnik:
382, Številka:
6675
Journal Article
Recenzirano
Biomedical microrobots could overcome current challenges in targeted therapies.
Artificial micro‐/nanoswimmers have various potential applications including minimally invasive diagnosis and targeted therapies, environmental sensing and monitoring, cell manipulation and analysis, ...and lab‐on‐a‐chip devices. Inspired by natural motile bacteria such as E. Coli, artificial bacterial flagella (ABFs) are one kind of magnetic helical microswimmers. ABFs can perform 3D navigation in a controllable fashion with micrometer precision under low‐strength rotating magnetic fields (<10 mT) and are promising tools for targeted drug delivery in vitro and in vivo. In this work, the successful wirelessly targeted and single‐cell gene delivery to human embryonic kidney (HEK 293) cells using ABFs loaded with plasmid DNA (pDNA) in vitro is demonstrated for the first time. The ABFs are functionalized with lipoplexes containing pDNA to generate functionalized ABFs (f‐ABFs). The f‐ABFs are steered wirelessly by low‐strength rotating magnetic fields and deliver the loaded pDNA into targeted cells. The cells targeted by f‐ABFs are successfully transfected by the transported pDNA and expressed the encoding protein. These f‐ABFs may also be useful for in vivo gene delivery and other applications such as sensors, actuators, cell biology, and lab‐on‐a‐chip environments.
Magnetic helical microswimmers, called artificial bacterial flagella (ABFs), can perform precise 3D navigation in liquid under low‐strength rotating magnetic fields, making themselves promising tools for targeted therapies. The ABFs are functionalized with lipoplexes containing plasmid DNA, and the successful wirelessly targeted gene delivery to human embryonic kidney cells in vitro using these functionalized ABFs is demonstrated.
Artificial bacterial flagella (ABFs) consist of helical tails resembling natural flagella fabricated by the self-scrolling of helical nanobelts and soft-magnetic heads composed of Cr/Ni/Au stacked ...thin films. ABFs are controlled wirelessly using a low-strength rotating magnetic field. Self-propelled devices such as these are of interest for in vitro and in vivo biomedical applications. Swimming tests of ABFs show a linear relationship between the frequency of the applied field and the translational velocity when the frequency is lower than the step-out frequency of the ABF. Moreover, the influences of head size on swimming velocity and the lateral drift of an ABF near a solid boundary are investigated. An experimental method to estimate the propulsion matrix of a helical swimmer under a light microscope is developed. Finally, swarm-like behavior of multiple ABFs controlled as a single entity is demonstrated.
Metachronal waves commonly exist in natural cilia carpets. These emergent phenomena, which originate from phase differences between neighbouring self-beating cilia, are essential for biological ...transport processes including locomotion, liquid pumping, feeding, and cell delivery. However, studies of such complex active systems are limited, particularly from the experimental side. Here we report magnetically actuated, soft, artificial cilia carpets. By stretching and folding onto curved templates, programmable magnetization patterns can be encoded into artificial cilia carpets, which exhibit metachronal waves in dynamic magnetic fields. We have tested both the transport capabilities in a fluid environment and the locomotion capabilities on a solid surface. This robotic system provides a highly customizable experimental platform that not only assists in understanding fundamental rules of natural cilia carpets, but also paves a path to cilia-inspired soft robots for future biomedical applications.
Magnetic helical microswimmers, also known as artificial bacterial flagella (ABFs), perform 3D navigation in various liquids under low-strength rotating magnetic fields by converting rotational ...motion to translational motion. ABFs have been widely studied as carriers for targeted delivery and release of drugs and cells. For in vivo/in vitro therapeutic applications, control over individual groups of swimmers within a swarm is necessary for several biomedical applications such as drug delivery or small-scale surgery. In this work, we present the selective control of individual swimmers in a swarm of geometrically and magnetically identical ABFs by modifying their surface chemistry. We confirm experimentally and analytically that the forward/rotational velocity ratio of ABFs is independent of their surface coatings when the swimmers are operated below their step-out frequency (the frequency requiring the entire available magnetic torque to maintain synchronous rotation). We also show that ABFs with hydrophobic surfaces exhibit larger step-out frequencies and higher maximum forward velocities compared to their hydrophilic counterparts. Thus, selective control of a group of swimmers within a swarm of ABFs can be achieved by operating the selected ABFs at a frequency that is below their step-out frequencies but higher than the step-out frequencies of unselected ABFs. The feasibility of this method is investigated in water and in biologically relevant solutions. Selective control is also demonstrated inside a Y-shaped microfluidic channel. Our results present a systematic approach for realizing selective control within a swarm of magnetic helical microswimmers.
Magnetically manipulated microrobots are demonstrated for targeted cell transportation. Full three‐dimensional (3D) porous structures are fabricated with an SU‐8 photoresist using a 3D laser ...lithography system. Nickel and titanium are deposited as a magnetic material and biocompatible material, respectively. The fabricated microrobots are controlled in the fluid by external magnetic fields. Human embryonic kidney 239 (HEK 239) cells are cultivated in the microrobot to show the possibility for targeted cell transportation.
A simple and general fabrication method for helical swimming micromachines by direct laser writing and e‐beam evaporation is demonstrated. The magnetic helical devices exhibit varying magnetic shape ...anisotropy, yet always generate corkscrew motion using a rotating magnetic field. They also exhibit good swimming performance and are capable of pick‐and‐place micromanipulation in 3D. Cytotoxicity of the devices was investigated using mouse myoblasts.
Variable stiffness (VS) is an important feature that significantly enhances the dexterity of magnetic catheters used in minimally invasive surgeries. Existing magnetic catheters with VS consist of ...sensors, heaters, and tubular structures filled with low melting point alloys, which have a large stiffness change ratio but are toxic to humans. In this paper, a VS magnetic catheter is described for minimally invasive surgery; the catheter is based on a novel variable stiffness thread (VST), which is made of a conductive shape memory polymer (CSMP). The CSMP is nontoxic and simultaneously serves as a heater, a temperature sensor, and a VS substrate. The VST is made through a new scalable fabrication process, which consists of a dipping technique that enables the fabrication of threads with the desired electrical resistance and thickness (with a step size of 70 µm). Selective bending of a multisegmented VST catheter with a diameter of 2.0 mm under an external magnetic field of 20 mT is demonstrated. Compared to existing proof‐of‐concept VS catheters for cardiac ablation, each integrated VST segment has the lowest wall thickness of 0.75 mm and an outer diameter of 2.0 mm. The segment bends up to 51° and exhibits a stiffness change factor of 21.
A variable stiffness (VS) catheter made of a conductive shape memory polymer (CSMP) is developed. The CSMP used here is a nontoxic material that simultaneously serves as a heater and a temperature sensor while providing VS. The catheter, fabricated through a scalable process, exhibits a stiffness change factor of 21 and bends up to 51° under an external magnetic field.
Neurodegenerative diseases generally result in irreversible neuronal damage and neuronal death. Cell therapy shows promise as a potential treatment for these diseases. However, the therapeutic ...targeted delivery of these cells and the in situ provision of a suitable microenvironment for their differentiation into functional neuronal networks remain challenging. A highly integrated multifunctional soft helical microswimmer featuring targeted neuronal cell delivery, on‐demand localized wireless neuronal electrostimulation, and post‐delivery enzymatic degradation is introduced. The helical soft body of the microswimmer is fabricated by two‐photon lithography of the photocurable gelatin–methacryloyl (GelMA)‐based hydrogel. The helical body is then impregnated with composite multiferroic nanoparticles displaying magnetoelectric features (MENPs). While the soft GelMA hydrogel chassis supports the cell growth, and is degraded by enzymes secreted by cells, the MENPs allow for the magnetic transportation of the bioactive chassis, and act as magnetically mediated electrostimulators of neuron‐like cells. The unique combination of the materials makes these microswimmers highly integrated devices that fulfill several requirements for their future translation to clinical applications, such as cargo delivery, cell stimulation, and biodegradability. The authors envision that these devices will inspire new avenues for targeted cell therapies for traumatic injuries and diseases in the central nervous system.
Biodegradable soft magnetoelectric microswimmers are fabricated using a 3D‐printing technique. These microswimmers can perform targeted delivery of neuron‐like cells and induce neuronal differentiation of these cells under different magnetic stimulation modes. This combinatorial technique is a significant step towards highly integrated microrobots, and may open up new avenues for cell therapies.
Functional compound micromachines are fabricated by a design methodology using 3D direct laser writing and selective physical vapor deposition of magnetic materials. Microtransporters with a ...wirelessly controlled Archimedes screw pumping mechanism are engineered. Spatiotemporally controlled collection, transport, and delivery of micro particles, as well as magnetic nanohelices inside microfluidic channels are demonstrated.
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