Fernando Soto

Ultrasound-Propelled Nanoporous Gold Wire for Efficient Drug Loading and Release

Ultrasound (US)-powered nanowire motors based on nanoporous gold segment are developed for increasing the drug loading capacity. The new highly porous nanomotors are characterized with a tunable pore size, high surface area, and high capacity for the drug payload. These nanowire motors are prepared by template membrane deposition of a silver-gold alloy segment followed by dealloying the silver component. The drug doxorubicin (DOX) is loaded within the nanopores via electrostatic interactions with an anionic polymeric coating. The nanoporous gold structure also facilitates the near-infrared (NIR) light controlled release of the drug through photothermal effects. Ultrasound-driven transport of the loaded drug toward cancer cells followed by NIR-light triggered release is illustrated. The incorporation of the nanoporous gold segment leads to a nearly 20-fold increase in the active surface area compared to common gold nanowire motors. It is envisioned that such US-powered nanomotors could provide a new approach to rapidly and efficiently deliver large therapeutic payloads in a target-specific manner.

Reversible Swarming and Separation of Self-Propelled Chemically Powered Nanomotors under Acoustic Fields

The collective behavior of biological systems has inspired efforts toward the controlled assembly of synthetic nanomotors. Here we demonstrate the use of acoustic fields to induce reversible assembly of catalytic nanomotors, controlled swarm movement, and separation of different nanomotors. The swarming mechanism relies on the interaction between individual nanomotors and the acoustic field, which triggers rapid migration and assembly around the nearest pressure node. Such on-demand assembly of catalytic nanomotors is extremely fast and reversible. Controlled movement of the resulting swarm is illustrated by changing the frequency of the acoustic field. Efficient separation of different types of nanomotors, which assemble in distinct swarming regions, is illustrated. The ability of acoustic fields to regulate the collective behavior of catalytic nanomotors holds considerable promise for a wide range of practical applications.

Acoustically Propelled Nanomotors for Intracellular siRNA Delivery

An effective intracellular gene silencing strategy based on acoustically propelled nanowires modified with an interfering RNAs (siRNA) payload is described. The gold nanowires (AuNW) are wrapped with a Rolling Circle Amplification (RCA) DNA strand, which serves to anchor the siRNA therapy. The ultrasound (US)-powered propulsion of the AuNW leads to fast internalization and rapid intracellular movement and hence to an accelerated siRNA delivery and silencing response. To optimize the micromotor gene silencing procedure, the influence of motion, time, and siRNA dosage was investigated, leading up to a 94% silencing after few minutes treatment with US-propelled siRNA-AuNWs, and to a dramatic (∼13-fold) improvement in the silencing response compared to the static modified nanowires. The ability of the nanomotor-based method for gene silencing has been demonstrated by measuring the GFP silencing response in two different cell lines (HEK-293 and MCF-7) and using detailed control experiments. The viability of the cells after the nanomotors treatment was examined using the MCF-7 cancer cell line. The use of DNA structures carried by the US-propelled nanomotors for gene silencing represents an efficient tool that addresses the challenges associated with RNA transportation and intracellular delivery. Future implementation of nanomachines in gene therapy applications can be expanded into a co-delivery platform for therapeutics.

Lysozyme-Based Antibacterial Nanomotors

An effective and rapid bacterial killing nanotechnology strategy based on lysozyme-modified fuel-free nanomotors is demonstrated. The efficient antibacterial property of lysozyme, associated with the cleavage of glycosidic bonds of peptidoglycans present in the bacteria cell wall, has been combined with ultrasound (US)-propelled porous gold nanowire (p-AuNW) motors as biocompatible dynamic bacteria nanofighters. Coupling the antibacterial activity of the enzyme with the rapid movement of these p-AuNWs, along with the corresponding fluid dynamics, promotes enzyme-bacteria interactions and prevents surface aggregation of dead bacteria, resulting in a greatly enhanced bacteria-killing capability. The large active surface area of these nanoporous motors offers a significantly higher enzyme loading capacity compared to nonporous AuNWs, which results in a higher antimicrobial activity against Gram-positive and Gram-negative bacteria. Detailed characterization studies and control experiments provide useful insights into the underlying factors controlling the antibacterial performance of the new dynamic bacteria nanofighters. Rapid and effective killing of the Gram-positive Micrococcus lysodeikticus bacteria (69-84% within 1-5 min) is demonstrated.

Enteric Micromotor Can Selectively Position and Spontaneously Propel in the Gastrointestinal Tract

The gastrointestinal (GI) tract, which hosts hundreds of bacteria species, becomes the most exciting organ for the emerging microbiome research. Some of these GI microbes are hostile and cause a variety of diseases. These bacteria colonize in different segments of the GI tract dependent on the local physicochemical and biological factors. Therefore, selectively locating therapeutic or imaging agents to specific GI segments is of significant importance for studying gut microbiome and treating various GI-related diseases. Herein, we demonstrate an enteric micromotor system capable of precise positioning and controllable retention in desired segments of the GI tract. These motors, consisting of magnesium-based tubular micromotors coated with an enteric polymer layer, act as a robust nanobiotechnology tool for site-specific GI delivery. The micromotors can deliver payload to a particular location via dissolution of their enteric coating to activate their propulsion at the target site toward localized tissue penetration and retention.

Micromotor-Based Energy Generation†

A micromotor-based strategy for energy generation, utilizing the conversion of liquid-phase hydrogen to usable hydrogen gas (H2), is described. The new motion-based H2-generation concept relies on the movement of Pt-black/Ti Janus microparticle motors in a solution of sodium borohydride (NaBH4) fuel. This is the first report of using NaBH4 for powering micromotors. The autonomous motion of these catalytic micromotors, as well as their bubble generation, leads to enhanced mixing and transport of NaBH4 towards the Pt-black catalytic surface (compared to static microparticles or films), and hence to a substantially faster rate of H2 production. The practical utility of these micromotors is illustrated by powering a hydrogen-oxygen fuel cell car by an on-board motion-based hydrogen and oxygen generation. The new micromotor approach paves the way for the development of efficient on-site energy generation for powering external devices or meeting growing demands on the energy grid.

Self-propelled screen-printable catalytic swimmers

A highly versatile 2D screen-printing fabrication of nature-inspired fish swimmers is described. The new screen-printing approach offers large-scale cost-effective fabrication of efficient multi-functional chemically-powered motors. Diverse fish architectures, consisting of several predesigned printed layers, including the mid-body, head, tail, and an entire fish, are achieved by printing different functional inks through the corresponding patterned stencils. The 2D fish-printing approach allows fine control of the shape, size, functionality and performance of the resulting fish swimmers. In particular, different functionalities can be incorporated at specific areas by sequential printing of specific layers based on different modified inks. For example, printing of catalytic tails containing various Pt loadings has been used to prepare fish with different propulsion efficiencies. Inks based on activated carbon powder have been used for accelerated removal of chemical pollutants. Nickel-containing carbon ink has been used for magnetic control of the fish directionality. This screen-printing fabrication route can be readily extended for incorporating other functional materials into one swimmer structure. Such a versatile, simple, scalable, fast, and cost-effective approach holds considerable promise for creating biomimetic swimmers with different properties for diverse practical applications.

Hybrid biomembrane–functionalized nanorobots for concurrent removal of pathogenic bacteria and toxins

Nanorobots with red blood cell–platelet hybrid membranes accelerated targeting and detoxification of biological threats. With the rapid advancement of robotic research, it becomes increasingly interesting and important to develop biomimetic micro- or nanorobots that translate biological principles into robotic systems. We report the design, construction, and evaluation of a dual–cell membrane–functionalized nanorobot for multipurpose removal of biological threat agents, particularly concurrent targeting and neutralization of pathogenic bacteria and toxins. Specifically, we demonstrated ultrasound-propelled biomimetic nanorobots consisting of gold nanowires cloaked with a hybrid of red blood cell (RBC) membranes and platelet (PL) membranes. Such hybrid cell membranes have a variety of functional proteins associated with human RBCs and PLs, which give the nanorobots a number of attractive biological capabilities, including adhesion and binding to PL-adhering pathogens (e.g., Staphylococcus aureus bacteria) and neutralization of pore-forming toxins (e.g., α-toxin). In addition, the biomimetic nanorobots displayed rapid and efficient prolonged acoustic propulsion in whole blood, with no apparent biofouling, and mimicked the movement of natural motile cells. This propulsion enhanced the binding and detoxification efficiency of the robots against pathogens and toxins. Overall, coupling these diverse biological functions of hybrid cell membranes with the fuel-free propulsion of the nanorobots resulted in a dynamic robotic system for efficient isolation and simultaneous removal of different biological threats, an important step toward the creation of a broad-spectrum detoxification robotic platform.

Topographical Manipulation of Microparticles and Cells with Acoustic Microstreaming

Precise and reproducible manipulation of synthetic and biological microscale objects in complex environments is essential for many practical biochip and microfluidic applications. Here, we present an attractive acoustic topographical manipulation (ATM) method to achieve efficient and reproducible manipulation of diverse microscale objects. This new guidance method relies on the acoustically induced localized microstreaming forces generated around microstructures, which are capable of trapping nearby microobjects and manipulating them along a determined trajectory based on local topographic features. This unique phenomenon is investigated by numerical simulations examining the local microstreaming in the presence of microscale boundaries under the standing acoustic wave. This method can be used to manipulate a single microobject around a complex structure as well as collectively manipulate multiple objects moving synchronously along complicated shapes. Furthermore, the ATM can serve for automated maze solving by autonomously manipulating microparticles with diverse geometries and densities, including live cells, through complex maze-like topographical features without external feedback, particle modification, or adjustment of operational parameters.

Noninvasive Transdermal Delivery System of Lidocaine Using an Acoustic Droplet-Vaporization Based Wearable Patch

Current technologies for managing acute and chronic pain have focused on reducing the time required for achieving high therapeutic efficiency. Herein a wearable transdermal patch is introduced, employing an acoustic droplet vaporization (ADV) methodology, as an effective noninvasive transdermal platform, for a fast local delivery of the anesthetic agent lidocaine. The skin-worn patch consists of a flexible drug reservoir containing hundreds of micropores loaded with lidocaine, and mixed with the perfluorocarbon (PFC) emulsion. The ultrasound-triggered vaporization of the PFC emulsion provides the necessary force to breach dermal barriers. The drug release kinetics of our model was investigated by measuring the amount of lidocaine that passed through phantom tissue and pigskin barriers. The ADV platform increases the payload skin penetration resulting in shorter treatment times compared to passive diffusion or ultrasound alone, holding considerable promise for addressing the delayed therapeutic action and slow pain relief of existing delivery protocols. It is envisioned that the integration of ADV-based transdermal devices could be expanded to the depth-dependent delivery of other pain management, vaccines, and gene therapy modalities.