Transient Mild Photothermia Improves Therapeutic Performance of Oral Nanomedicines with Enhanced Accumulation in the Colitis Mucosa.

The treatment outcomes of oral medications against ulcerative colitis (UC) have long been restricted by low drug accumulation in the colitis mucosa and subsequent unsatisfactory therapeutic efficacy. Here, high-performance pluronic F127 (P127)-modified gold shell (AuS)-polymeric core nanotherapeutics loading with curcumin (CUR) is constructed. Under near-infrared irradiation, the resultant P127-AuS@CURs generate transient mild photothermia (TMP; ≈42 °C, 10 min), which facilitates their penetration through colonic mucus and favors multiple cellular processes, including cell internalization, lysosomal escape, and controlled CUR release. This strategy relieves intracellular oxidative stress, improves wound healing, and reduces immune responses by polarizing the proinflammatory M1-type macrophages to the anti-inflammatory M2-type. Upon oral administration of hydrogel-encapsulating P127-AuS@CURs plus intestinal intralumen TMP, their therapeutic effects against acute and chronic UC are demonstrated to be superior to those of a widely used clinical drug, dexamethasone. The treatment of P127-AuS@CURs (+ TMP) elevates the proportions of beneficial bacteria (e.g., Lactobacillus and Lachnospiraceae), whose metabolites can also mitigate colitis symptoms by regulating genes associated with antioxidation, anti-inflammation, and wound healing. Overall, the intestinal intralumen TMP offers a promising approach to enhance the therapeutic outcomes of noninvasive medicines against UC.

Self-propelled predator-prey of swarming Janus micromotors.

It is a long-standing challenge to accomplish bionic microrobot that acts in a similar way of white blood cell, chasing bacteria in complex environment. Without an effective external control field, most swarming microrobots systems are usually unable to perform directional movement and redirect their motion to capture the target. Here we report the predatory-prey dynamics of self-propelled clusters of Janus micromotors. The active cluster generates an oxygen bubbles cloud around itself by decomposing H2O2, which levitated it above the substrate, enhancing its mobility in solution to wander around to devour other clusters. The fast decomposition of H2O2 also induced a tubular low-concentration zone that bridges two clusters far separated from each other, resulting in a diffusio-osmotic pressure that drives the two clusters to meet. This predatory-prey phenomena mimic white blood cells chasing bacteria and swarming flocks in nature, shedding light on emergent collective intelligence in biology.

Biodegradable magnesium fuel-based Janus micromotors with surfactant induced motion direction reversal.

The speed and motion directionality of bubble-propelled micromotors is dependent on bubble lifetime, bubble formation frequency and bubble stabilization. Absence and presence of bubble stabilizing agents should significantly influence speed and propulsion pattern of a micromotor, especially for fast-diffusing molecules like hydrogen. This study demonstrates a fully biodegradable Janus structured micromotor, propelled by hydrogen bubbles generated by the chemical reaction between hydrochloric acid and magnesium. Six different concentrations of hydrochloric acid and five different concentrations of the surfactant Triton X-100 were tested, which also cover the critical micelle concentration at a pH corresponding to an empty stomach. The Janus micromotor reverses its propulsion direction depending on the availability and concentration of a surfactant. Upon surfactant-free condition, the Janus micromotor is propelled by bubble cavitation, causing the micromotor to be pulled at high speed for short time intervals into the direction of the imploding bubble and thus backwards. In case of available surfactant above the critical micelle concentration, the Janus micromotor is pushed forward by the generated bubbles, which emerge at high frequency and form a bubble trail. The finding of the propulsion direction reversal effect demonstrates the importance to investigate the motion properties of artificial micromotors in a variety of different environments prior to application, especially with surfactants, since biological media often contain large amounts of surface-active components.

Rational Design of Polymer Conical Nanoswimmers with Upstream Motility.

Utilizing bottom-up controllable molecular assembly, the bio-inspired polyelectrolyte multilayer conical nanoswimmers with gold-nanoshell functionalization on different segments are presented to achieve the optimal upstream propulsion performance. The experimental investigation reveals that the presence of the gold nanoshells on the big openings of the nanoswimmers could not only bestow efficient directional propulsion but could also minimize the impact from the external flow. The gold nanoshells at the big openings of nanoswimmers facilitate the acoustically powered propulsion against a flow velocity of up to 2.00 mm s-1, which is higher than the blood velocity in capillaries and thus provides a proof-of-concept design for upstream nanoswimmers.

Torque-Driven Orientation Motion of Chemotactic Colloidal Motors.

We report a direct experimental observation of the torque-driven active reorientation of glucose-fueled flasklike colloidal motors to a glucose gradient exhibiting a positive chemotaxis. These streamlined flasklike colloidal motors are prepared by combining a hydrothermal synthesis and a vacuum infusion and can be propelled by an enzymatic cascade reaction in the glucose fuel. Their flasklike architecture can be used to recognize their moving posture, and thus the dynamic glucose-gradient-induced alignment and orientation-dependent motility during positive chemotaxis can be examined experimentally. The chemotactic mechanism is that the enzymatic reactions inside lead to the glucose acid gradient and the glucose gradient which generate two phoretic torques at the bottom and the opening respectively, and thus continuously steer it to the glucose gradient. Such glucose-fueled flasklike colloidal motors resembling the chemotactic capability of living organisms hold considerable potential for engineering active delivery vehicles in response to specific chemical signals.

Defect dynamics in clusters of self-propelled rods in circular confinement.

Rod-shaped active micro/nano-particles, such as bacterial and bipolar metallic micro/nano-motors, demonstrate novel collective phenomena far from the equilibrium state compared to passive particles. We apply a simulation approach --dissipative particle dynamics (DPD)-- to explore the collectively ordered states of self-propelled rods (SPRs). The SPRs are confined in a finite circular zone and repel each other when two rods touch each other. It is found that for a long enough rods system, the global vortex patterns, dynamic pattern oscillation between hedgehog pattern and vortex pattern, and hedgehog patterns are observed successively with increasing active force Fa. For the vortex pattern, the total interaction energy between the rods U is linear with active force Fa, i.e., U ∼ Fa . While the relation U ∼ Fa2 is obtained for the hedgehog structure. It is observed that a new hedgehog pattern with one defect core is created by two ejections of polar cluster in opposite directions from the original hedgehog pattern, and then merges into one through the diffusion of the two aggregates, i.e., the creation and annihilation of topological charges.

Gold-Nanoshell-Functionalized Polymer Nanoswimmer for Photomechanical Poration of Single-Cell Membrane.

We report an ultrasound-driven gold-nanoshell-functionalized polymer multilayer tubular nanoswimmer that can photomechanically perforate the membrane of a cancer cell by assistance of near-infrared (NIR) light. The nanoswimmers were constructed by a template-assisted layer-by-layer technique and subsequent functionalization of Au nanoshells inside the big opening. The nanoswimmers exhibit efficient and controllable movement toward target cells through the manipulation of the acoustic field. Next, the nanoswimmers with end-on attachment onto the HeLa cells achieve the poration of the cell membrane within 0.1 s under the irradiation of NIR light. The experimental and theoretical results suggest that the instantaneous photothermal effect provides enough photomechanical force to open the cell membrane. Such NIR-light-assisted nanoswimmers-enabled cell membrane poration possesses various advantages including active targeting, short time, and precision in single cells that conventional chemical and physical cell poration techniques could not achieve and, thus, provides considerable promise in a variety of biomedical applications such as gene delivery and artificial insemination.

Gold nanorods based multicompartment mesoporous silica composites as bioagents for highly efficient photothermal therapy.

Photothermal therapy (PTT) based on photothermal effect of the gold nanostructures, has been widely applied as a noninvasive therapy approach in cancer treatment. However, bare Au nanoparticles are not stable enough during the irradiation process, and cannot harvest sufficient energy to kill tumor cells. To improve this, we have fabricated a stable bioagent by loading gold nanorods (AuNRs) into multicompartment mesoporous silica nanoparticles (MMSNs) for the photothermal therapy. The procedure is that when AuNRs entrapped in MMSNs are irradiated by a laser in the near-infrared region of 808 nm, the hyperthermia produced by the assembled composites is strong enough to damage tumor tissues directly. Both experiments in vitro and in vivo demonstrate that the nanocomposites are perfect candidates as PTT agents for the cancer treatment with a high efficiency. Furthermore, it is found that the nanocomposites have good photostability and consistent temperature fluctuation over 11 on/off cycles with irradiation which the pure AuNRs will not have.

A Bubble-Dragged Catalytic Polymer Microrocket.

We report the bubble dragged microrocket consisting of functionalized multilayer polymer covered asymmetrically by platinum nanoparticles. The microrocket is pushed back during bubble growth over a small step and dragged forward over a big step during bubble explosion. Each bubble explosion induced a shock wave of gas which propagates in water at ultrafast speed. The bubble dragged microrocket can move along an approximate straight line instead of a fluctuating circle which is the trajectory of a bubble-pushed microrocket in most cases, which makes it a promising candidate for drug delivery and simulating rod-shaped bacteria.

Magnetically-guided hydrogel capsule motors produced via ultrasound assisted hydrodynamic electrospray ionization jetting.

Hydrogel capsules are a potential candidate for drug delivery and an interesting alternative to polyelectrolyte multilayer capsules which are under investigation since 20 years. Recently introduced polyelectrolyte complex capsules produced by spraying are non-biodegradable and not biocompatible, which limits their practical application, while biodegradable alginate capsules require complex coaxial electrospray ionization jetting. In this work, biodegradable alginate capsules cross-linked by calcium are successfully produced by hydrodynamic electrospray ionization jetting with the assistance of low frequency ultrasound. The size and shape of most capsules show significant differences with respect to different spraying distance, spraying mode, electrode shape and spraying concentration. Capsules in the shape of vase, mushrooms and spheres were successfully produced. Average capsule size can be adjusted from 10 µm to 2 mm. These capsules are used to encapsulate a model drug. Encapsulated paramagnetic particles enable defined directional motion under the propulsion of a rotating magnetic field, while model drugs can be released by ultrasound.

Magnetically-propelled hydrogel particle motors produced by ultrasound assisted hydrodynamic electrospray ionization jetting.

One of the most promising future applications of hydrogels is drug delivery. The hydrogels act as a biomedical cargo model to reach the target and release drugs to cure diseases. This application requires no side effects of the hydrogel and the ability to pass through porous media (e.g. membranes, interstitial tissue etc.) with nanoscaled channels. At the same time, the hydrogel must be mass-producible in an economic way. In this work, we show that hydrodynamic electrospray ionization jetting combined with ultrasound can fulfill these high requirements. This method can produce mucoadhesive micro-/nano-particles, which are small enough to pass through the gastrointestinal epithelium. The average size of the produced particles is exactly predictable by controlling the spraying distance, spraying mode, alginate concentration, ultrasound bath frequency and counter electrode shape. These micro-/nano-particles are loaded with biocompatible magnetite nanoparticles, and propelled by a rotating magnetic field between 5 to 20 m T and a frequency from 1 Hz to 100 Hz. These rotating micro-/nano-particle motors perform directional motion in solution, offering a promising possibility for magnetically controlled drug delivery.

Bubble-Pair Propelled Colloidal Kayaker.

We report a hollow dumbbell-shaped manganese dioxide (MnO2) colloidal kayaker capable of converting a pair of breathing oxygen bubbles into self-propelled movement. The bubble pair generated by catalytic decomposition of hydrogen peroxide fuel grew either synchronously or asynchronously, driving the colloidal kayaker to move along a fluctuating circle. The synchronous or asynchronous breathing mode of bubble pair is governed by the asymmetric catalytic sites of the colloidal kayakers. This imbalanced distribution of bubble propulsion force generates the driving force and the centripetal force on the colloidal kayaker. The dynamics of colloidal kayakers is well-described by the overdamped Langevin equation and fluid field simulation. Such bubble-pair propelled colloidal kayakers could advance applications of catalytic nanomotors, offering effective implementation for diverse tasks for a wide range of practical applications.

Hydrodynamic electrospray ionization jetting of calcium alginate particles: effect of spray-mode, spraying distance and concentration.

Hydrodynamic electrospray ionization jetting was applied for generating and characterizing calcium cross-linked alginate microparticles. These microparticles show different diameters and aspect ratios for three electrospray modes (dripping, conejet and multijet modes), four spraying distances (5, 10, 15 and 20 cm), and six spraying concentrations. Comparing the three different electrospray modes, we found that the conejet mode results in the smallest particle diameters, lowest aspect ratio and smallest variations over the parameter space mentioned above. For all spraying modes, the resultant particle diameters become independent of the spraying distance at a sprayed solute concentration ≥ 2.5%. The aspect ratio of microparticles varies significantly for different spraying modes and distances. An increasing aspect ratio of all spray modes was determined for sodium alginate spraying concentrations ≤ 1.5% and spraying distances of 20 cm; this phenomenon can be explained with the chain ejection effect. This systematic investigation offers a basic database for industrial applications of hydrodynamic electrospray ionization.

Capillary flow and mechanical buckling in a growing annular bacterial colony.

A growing bacterial colony is a dense suspension of an increasing number of cells capable of individual as well as collective motion. After inoculating Pseudomonas aeruginosa over an annular area on an agar plate, we observe the growth and spread of the bacterial population, and model the process by considering the physical effects that account for the features observed. Over a course of 10-12 hours, the majority of bacteria migrate to and accumulate at the edges. We model the capillary flow induced by imbalanced evaporation flux as the cause for the accumulation, much like the well-known coffee stain phenomenon. Simultaneously, periodic buckles or protrusions occur at the inner edge. These buckles indicate that the crowding bacteria produce a jam, transforming the densely packed population at the inner edge to a solid state. The continued bacterial growth produces buckles. Subsequently, a ring of packed bacteria behind the inner edge detach from it and break into pieces, forming bacterial droplets. These droplets slowly coalesce while they continually grow and collectively surf on the agar surface in the region where the colony had previously spread over. Our study shows a clear example of how fluid dynamics and elasto-mechanics together govern the bacterial colony pattern evolution.

Light-Activated Active Colloid Ribbons.

We report a dynamic self-organization of self-propelled peanut-shaped hematite motors from non-equilibrium driving forces where the propulsion can be triggered by blue light. They result in one-dimensional, active colloid ribbons with a positive phototactic characteristic. The motion of colloid motors is ascribed to the diffusion-osmotic flow in a chemical gradient by the photocatalytic decomposition of hydrogen peroxide fuel. We show that self-propelled peanut-shaped colloids readily form one-dimensional, slithering ribbon structures under the out-of-equilibrium collisions. This self-organization intrinsically results from the competition among the osmotically driven motion, the phoretic attraction and the inherent magnetic moments. The giant size number fluctuation in colloid ribbons is observed above a critical point 4.1 % of the surface density of colloid motors. Such phototactic colloid ribbons may provide a model system to understand the emergence of function in biological systems and have potential to construct bioinspired active materials based on different active building blocks.

A Light-Activated Explosive Micropropeller.

Self-propelled micro/nanomotors possess tremendous exciting promise in diverse fields. We describe an asymmetric, fuel-free and near-infrared light-powered torpedo micromotor, which is constructed by using a porous membrane-assisted layer-by-layer sol-gel method to form silica multilayer inside the pores, following by the deposition of gold nanoparticles on one end of the pores. In the absence of chemical fuels, the high propulsion of microtorpedoes under illumination of near-infrared light is owing to the photo-thermal effect of gold clusters, generating a thermal gradient inside the microtorpedoes. The speed of microtorpedoes is dependent on the laser powers and media. More interestingly, such fuel free-powered microtorpedoes could explode triggered by higher laser power at the predefined site and thus provide a new platform for future biomedical applications.

Self-thermophoretic motion of controlled assembled micro-/nanomotors.

As artificial active colloids, micro-/nanomotors (MNMs) can convert energy from the environment into mechanical motion in different fluids, showing potential applications in diverse fields such as targeted drug delivery and photothermal therapy. However, chemical fuels for typical catalytic MNMs, e.g., hydrogen peroxide, are highly toxic to organisms, and thus fuel-free MNMs are required. Recently, we have developed near-infrared light (NIR) propelled MNMs through integrating plasmonic gold nanoshells into nanoparticles or layer-by-layer assemblies in an asymmetric manner. In this perspective, we give an account of self-thermophoresis motion of these NIR-powered MNMs. The design of the motor architectures, as well as the theoretical study on the propulsion mechanism, is highlighted. We believe that the insights into self-thermophoretic motion would pave the way to access powerful MNMs for future applications and to explore interesting collective behaviors of active matter.

Influence of Physical Effects on the Swarming Motility of Pseudomonas aeruginosa.

Many species of bacteria can spread over a moist surface via a particular form of collective motion known as "surface swarming". This form of motility is typically studied by inoculating bacteria on a gel formed by 0.4-1.5% agar, which contains essential nutrients for their growth and proliferation. Using Pseudomonas aeruginosa and its pili-less mutant, ΔPilA, we investigate physical factors that either facilitate or restrict the swarming motility, measured by the rate of increase in area covered by a spreading bacterial colony, i.e., a swarm. The wild-type colony spreads over the agar surface in highly branched structures. The pili-less mutant fills up the area more fully as it spreads, but it also produces numerous and fragmented branches, or tendrils, at the swarm front. Whereas additional surfactants enhance swarming, increasing the agar percentage, adding extra salt or sugar or incorporating viscous agents in the agar matrix all decrease swarming, supporting the conclusion that swarming motility is restricted by the surface tension at the swarm front and swarm growth is limited by the rate of water supply from within the agar gel. The physical basis elaborated through this study provides a useful framework for understanding the swarming behavior of numerous species of bacteria.

Near Infrared Light-Powered Janus Mesoporous Silica Nanoparticle Motors.

We describe fuel-free, near-infrared (NIR)-driven Janus mesoporous silica nanoparticle motors (JMSNMs) with diameters of 50, 80, and 120 nm. The Janus structure of the JMSNMs is generated by vacuum sputtering of a 10 nm Au layer on one side of the MSNMs. Upon exposure to an NIR laser, a localized photothermal effect on the Au half-shells results in the formation of thermal gradients across the JMSNMs; thus, the generated self-thermophoresis can actively drive the nanomotors to move at an ultrafast speed, for instance, up to 950 body lengths/s for 50 nm JMSNMs under an NIR laser power of 70.3 W/cm(2). The reversible "on/off" motion of the JMSNMs and their directed movement along the light gradient can be conveniently modulated by a remote NIR laser. Moreover, dynamic light scattering measurements are performed to investigate the coexisting translational and rotational motion of the JMSNMs in the presence of both self-thermophoretic forces and strong Brownian forces. These NIR-powered nanomotors demonstrate a novel strategy for overcoming the necessity of chemical fuels and exhibit a significant improvement in the maneuverability of nanomotors while providing potential cargo transportation in a biofriendly manner.

Recent Progress on Bioinspired Self-Propelled Micro/Nanomotors via Controlled Molecular Self-Assembly.

The combination of bottom-up controllable self-assembly technique with bioinspired design has opened new horizons in the development of self-propelled synthetic micro/nanomotors. Over the past five years, a significant advances toward the construction of bioinspired self-propelled micro/nanomotors has been witnessed based on the controlled self-assembly technique. Such a strategy permits the realization of autonomously synthetic motors with engineering features, such as sizes, shapes, composition, propulsion mechanism, and function. The construction, propulsion mechanism, and movement control of synthetic micro/nanomotors in connection with controlled self-assembly in recent research activities are summarized. These assembled nanomotors are expected to have a tremendous impact on current artificial nanomachines in future and hold potential promise for biomedical applications including drug targeted delivery, photothermal cancer therapy, biodetoxification, treatment of atherosclerosis, artificial insemination, crushing kidney stones, cleaning wounds, and removing blood clots and parasites.