Zhiguang Wu

Self‐Propelled Polymer‐Based Multilayer Nanorockets for Transportation and Drug Release

There is a growing effort in the scientific community to design and fabricate versatile artificial nanomotors propelled by selfgenerated forces, because they have potential in the field of directed drug delivery, roving sensors, isolation and detection of targets, active biomimetic systems, and other emerging applications. Inspired by the nanoscale linear biomotors (for example, kinesins), which can autonomously move in aqueous solution and are powered by spontaneous hydrolysis of biological energy units, substantial efforts towards the design of chemically powerful synthetic motors at the microand nanoscale have recently demonstrated the ability of converting chemical energy into autonomous motion based on a fuel solution (for example, aqueous hydrogen peroxide solution). To explain the motion and energy transfer process in these chemically powered systems, several mechanisms, including bubble propulsion, interfacial tension gradients, self-electrophoresis, self-diffusiophoresis, osmotic propulsion, ultrasound propulsion, and polymerization reactions were proposed. Among diverse synthetic microengines, chemically powered tubular micromotors prepared by the rolled-up technique and template electrosynthesis have displayed a high speed and the controllable directionality of the movement compared to bimetal nanorods or Janus microsphere motors. These rocket-like microengines are capable of the pick-up, transportation, and release of various cargoes, including polymer particles, nucleic acids, cancer cells, and bacteria. However, they still have some inherent limitations, such as complex preparation technology, difficulty of surface modification, and poor biocompatibility or biodegradability. Moreover, it is required in many cases that synthetic motors can encapsulate, transport, and release targeted substances by themselves in an easy and controllable way and have good biocompatibility and biodegradability, particularly in both biomedical and environmental fields. Therefore, it still remains a challenge to develop new fabrication methods and expand the diversity of the building components. Herein, we describe the successful construction of a welldefined polymer multilayer tubular nanomotor through the nanoporous template-assisted layer-by-layer (LbL) assembly. It is pointed out that the pore channels of the used nanoporous template are asymmetric so that the control of the movement directionality can be conveniently achieved. Platinum nanoparticles (PtNPs) with a uniform size and shape are assembled within the inner surface of LbLassembled nanotubes and catalytically decompose hydrogen peroxide (as fuel) to water and oxygen. The resulting oxygen bubbles (propulsion gas) move towards the large opening, releasing oxygen bubbles from this end and in turn pushing the nanotube along (miniaturized rocket). One advantage of our approach is that not only can the length, wall thickness, and outside and inner diameters of the resulting nanotubes be controlled at the nanoscale, but also the wall properties can be conveniently varied by assembling the corresponding components, such as polymers, nanoparticles, proteins, and inorganic or organic functional molecules. The LbLassembled nanostructures can thus preserve the function of various building units, and multifunctional nanostructures can then easily be obtained by assembling the corresponding functional units. More interestingly, it has been demonstrated that the LbL-assembled multilayers are responsive to external chemical, physical, or biological stimuli. Until now, most of research has focused on the LbL-assembled multilayer nanotubes with the engineered features and functions as well as on their application in biomedical fields, but they still have not been explored as autonomous motor systems. We expect that the first demonstration of highly efficient and controllable autonomous LbL-assembled tubes provide a promising platform for the development of multifunctional nanorockets, performing drug encapsulation and release and active transportation without the need of external resources. The tubular nanorockets were fabricated by a nanoporous template-assisted LbL assembly (Figure 1a). Briefly, two biodegradable natural polysaccharides, positively charged chitosan (CHI) and negatively charged sodium alginate (ALG), were alternatively absorbed into track-etched porous polycarbonate (PC) membranes with a thickness of about 10 mm and pore diameter of about 600 nm. After the 18 bilayers with ALG as the inner layer were obtained, preformed poly(diallyldimethylammonium chloride) (PDADMAC)-stabilized PtNPs were subsequently assembled into the template pores. Finally, well-dispersed PtNPmodified (CHI/ALG)18 nanotubes can be obtained after dissolution of the PC templates in CH2Cl2. Both transmission electron microscopy (TEM; Figure 1b) and scanning electron microscopy images (SEM: Figure 1c) of the resulting (CHI/ ALG)18-PtNP nanotubes show well-defined tubular struc[*] Z. Wu, Y. Wu, W. He, Dr. X. Lin, Prof. J. Sun, Prof. Q. He Key Lab for Microsystems and Microstructure Manufacturing The Academy of Fundamental and Interdisciplinary Sciences Harbin Institute of Technology, Harbin 150080 (China) E-mail: qianghe@hit.edu.cn

Autonomous Movement of Controllable Assembled Janus Capsule Motors

We demonstrate the first example of a self-propelled Janus polyelectrolyte multilayer hollow capsule that can serve as both autonomous motor and smart cargo. This new autonomous Janus capsule motor composed of partially coated dendritic platinum nanoparticles (Pt NPs) was fabricated by using a template-assisted layer-by-layer (LbL) self-assembly combined with a microcontact printing method. The resulting Janus capsule motors still retain outstanding delivery capacities and can respond to external stimuli for controllable encapsulation and triggered release of model drugs. The Pt NPs on the one side of the Janus capsule motors catalytically decompose hydrogen peroxide fuel, generating oxygen bubbles which then recoil the movement of the capsule motors in solution or at an interface. They could autonomously move at a maximum speed of above 1 mm/s (over 125 body lengths/s), while exerting large forces exceeding 75 pN. Also, these asymmetric hollow capsules can be controlled by an external magnetic field to achieve directed movement. This LbL-assembled Janus capsule motor system has potential in making smart self-propelling delivery systems.

Near-infrared light-triggered "on/off" motion of polymer multilayer rockets.

We describe an approach to modulating the on-demand motion of catalytic polymer-based microengines via near-infrared (NIR) laser irradiation. The polymer multilayer motor was fabricated by the template-assisted layer-by-layer assembly and subsequently deposition of platinum nanoparticles inside and a thin gold shell outside. Then a mixed monolayer of a tumor-targeted peptide and an antifouling poly(ethylene glycol) was functionalized on the gold shell. The microengines remain motionless at the critical peroxide concentration (0.1%, v/v); however, NIR illumination on the engines leads to a photothermal effect and thus rapidly triggers the motion of the catalytic engines. Computational modeling explains the photothermal effect and gives the temperature profile accordingly. Also, the photothermal effect can alone activate the motion of the engines in the absence of the peroxide fuel, implying that it may eliminate the use of toxic fuel in the future. The targeted recognition ability and subsequently killing of cancer cells by the photothermal effect under the higher power of a NIR laser were illustrated. Our results pave the way to apply self-propelled synthetic engines in biomedical fields.

Self-Propelled Polymer Multilayer Janus Capsules for Effective Drug Delivery and Light-Triggered Release

We present herein a novel hybrid, polymer-based motor that was fabricated by the template-assisted polyelectrolyte layer-by-layer (LbL) deposition of a thin gold layer on one side, followed by chemical immobilization of a catalytic enzyme. Such Janus capsule motors can self-propel at 0.1% peroxide fuel concentration at physiological temperature and have a higher speed as compared to Pt-based synthetic motors. They were exploited for encapsulation of the chemotherapeutic anticancer drug, doxorubicin, for navigation to target a cell layer by an external magnetic field, and for triggered drug release activated by NIR light. This work provides high potential in the development of multifunctional polymer-based engines for biomedical applications such as targeted drug delivery.

Self‐Propelled Micro‐/Nanomotors Based on Controlled Assembled Architectures

Synthetic micro-/nanomotors (MNMs) are capable of performing self-propelled motion in fluids through harvesting different types of energies into mechanical movement, with potential applications in biomedicine and other fields. To address the challenges in these applications, a promising strategy that combines controlled assembly (bottom-up approaches) with top-down approaches for engineering autonomous, multifunctionalized MNMs is under investigation, beginning in 2012. These MNMs, derived from layer-by-layer assembly or molecular self-assembly, display the advantages of: i) mass production, ii) response to the external stimuli, and iii) access to multifunctionality, biocompatibility, and biodegradability. The advance on how to integrate diverse functional components into different architectures based on controlled assemblies, to realize controlled fabrication, motion control (including the movement speed, direction, and state), and biomedical applications of MNMs, directed by the concept of nanoarchitectonics, are highlighted here. The remaining challenges and future research directions are also discussed.

Turning Erythrocytes into Functional Micromotors

Attempts to apply artificial nano/micromotors for diverse biomedical applications have inspired a variety of strategies for designing motors with diverse propulsion mechanisms and functions. However, existing artificial motors are made exclusively of synthetic materials, which are subject to serious immune attack and clearance upon entering the bloodstream. Herein we report an elegant approach that turns natural red blood cells (RBCs) into functional micromotors with the aid of ultrasound propulsion and magnetic guidance. Iron oxide nanoparticles are loaded into the RBCs, where their asymmetric distribution within the cells results in a net magnetization, thus enabling magnetic alignment and guidance under acoustic propulsion. The RBC motors display efficient guided and prolonged propulsion in various biological fluids, including undiluted whole blood. The stability and functionality of the RBC motors, as well as the tolerability of regular RBCs to the ultrasound operation, are carefully examined. Since the RBC motors preserve the biological and structural features of regular RBCs, these motors possess a wide range of antigenic, transport, and mechanical properties that common synthetic motors cannot achieve and thus hold considerable promise for a number of practical biomedical uses.

3D‐Printed Artificial Microfish

Hydrogel microfish featuring biomimetic structures, locomotive capabilities, and functionalized nanoparticles are engineered using a rapid 3D printing platform: microscale continuous -optical printing (μCOP). The 3D-printed -microfish exhibit chemically powered and magnetically guided propulsion, as well as highly efficient detoxification capabilities that highlight the technical versatility of this platform for engineering advanced functional microswimmers for diverse biomedical applications.

Biodegradable Protein-Based Rockets for Drug Transportation and Light-Triggered Release

We describe a biodegradable, self-propelled bovine serum albumin/poly-l-lysine (PLL/BSA) multilayer rocket as a smart vehicle for efficient anticancer drug encapsulation/delivery to cancer cells and near-infrared light controlled release. The rockets were constructed by a template-assisted layer-by-layer assembly of the PLL/BSA layers, followed by incorporation of a heat-sensitive gelatin hydrogel containing gold nanoparticles, doxorubicin, and catalase. These rockets can rapidly deliver the doxorubicin to the targeted cancer cell with a speed of up to 68 μm/s, through a combination of biocatalytic bubble propulsion and magnetic guidance. The photothermal effect of the gold nanoparticles under NIR irradiation enable the phase transition of the gelatin hydrogel for rapid release of the loaded doxorubicin and efficient killing of the surrounding cancer cells. Such biodegradable and multifunctional protein-based microrockets provide a convenient and efficient platform for the rapid delivery and controlled release of therapeutic drugs.

Magneto−Acoustic Hybrid Nanomotor

Efficient and controlled nanoscale propulsion in harsh environments requires careful design and manufacturing of nanomachines, which can harvest and translate the propelling forces with high spatial and time resolution. Here we report a new class of artificial nanomachine, named magneto-acoustic hybrid nanomotor, which displays efficient propulsion in the presence of either magnetic or acoustic fields without adding any chemical fuel. These fuel-free hybrid nanomotors, which comprise a magnetic helical structure and a concave nanorod end, are synthesized using a template-assisted electrochemical deposition process followed by segment-selective chemical etching. Dynamic switching of the propulsion mode with reversal of the movement direction and digital speed regulation are demonstrated on a single nanovehicle. These hybrid nanomotors exhibit a diverse biomimetic collective behavior, including stable aggregation, swarm motion, and swarm vortex, triggered in response to different field inputs. Such adaptive hybrid operation and controlled collective behavior hold considerable promise for designing smart nanovehicles that autonomously reconfigure their operation mode according to their mission or in response to changes in their surrounding environment or in their own performance, thus holding considerable promise for diverse practical biomedical applications of fuel-free nanomachines.

Superfast Near-Infrared Light-Driven Polymer Multilayer Rockets.

A gold nanoshell-functionalized polymer multilayer nanorocket performs self-propulsion upon the irradiation with NIR light in the absence of chemical fuel. Theoretical simulations reveal that the NIR light-triggered self-thermophoresis drives the propulsion of the nanorocket. The nanorocket also displays -efficient NIR light-triggered propulsion in -biofluids and thus holds considerable promise for various potential biomedical applications.