Efficient Click Synthesis of a Protonized and Reduction-Sensitive Amphiphilic Small-Molecule Prodrug Containing Camptothecin and Gemcitabine for a Drug Self-Delivery System.

Drug self-delivery systems consisting of small-molecule active drugs with nanoscale features for intracellular delivery without the need for additional polymeric carriers have drawn much attention recently. In this work, we proposed a highly efficient strategy to fabricate protonized and reduction-responsive self-assembled drug nanoparticles from an amphiphilic small-molecule camptothecin-ss-1,2,3-triazole-gemcitabine conjugate (abbreviated as CPT-ss-triazole-GEM) for combination chemotherapy, which was prepared via a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction. To obtain this drug-triazole-drug conjugate, we first prepared a CPT derivate containing a propargyl group linked with a disulfide group and a GEM derivate attached to an azide group. Subsequently, the two kinds of modified drugs were connected together through a CuAAC reaction between the alkynyl and azide groups to yield the CPT-ss-triazole-GEM prodrug. The characterizations of chemical structures of these intermediates and the final product were performed by 1H NMR, Fourier transform infrared, and liquid chromatography/mass spectrometry measurements. This amphiphilic small-molecule drug-triazole-drug conjugate displayed a high drug loading content, that is, 36.0% of CPT and 27.2% of GEM. This kind of amphiphilic small-molecule prodrugs could form spherical nanoparticles in an aqueous solution in the absence of any other polymeric carriers, in which the hydrophobic CPT formed the core of the nanoparticles, whereas the hydrophilic GEM and protonated 1,2,3-triazole group yielded the shell. In the tumor microenvironment, the prodrug nanoparticles could release both pristine drugs simultaneously. Under the conditions of pH 7.4, and pH 7.4 and 2 µM glutathione (GSH), the prodrug nanoparticles could maintain stability and only 7% of CPT was leaked. However, in a high-GSH environment (pH 7.4 and 10 mM GSH) with the same incubation time, the disulfide linkage would be dissociated and lead to about 34% of CPT release. The results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test demonstrated that these prodrug nanoparticles showed a higher cytotoxicity toward HepG2 cells than free CPT and free GEM on both 48 and 72 h of incubation. Both in vitro cellular uptake and flow cytometry results implied that these prodrug nanoparticles could be internalized by HepG2 cells with efficient drug release inside cells. The pharmacokinetics and tissue distribution of the prodrug showed a moderate half-life in vivo, and the prodrug peak concentration in most of the collected tissues appeared at 0.25 h after administration. In addition, the CPT-ss-triazole-GEM prodrug could not cross the blood-brain barrier. Even more important is the fact that there is no accumulation in tissues and a rapid elimination of this small-molecule prodrug could be achieved. In brief, this protonized and reduction-sensitive prodrug simultaneously binds both antitumor drugs and has good self-delivery behavior through the donor-acceptor interaction of the H-bonding ligand, that is, the 1,2,3-triazole group. It provides a new method for combined drug therapy.

Highly active and regioselective hydroaminomethylation of olefins catalyzed by Rh/sulfoxantphos with ZSM-5.

Rh-catalyzed hydroaminomethylation has been developed with acid sulfoxantphos and ZSM-5. Linear amines were obtained in good yields (71-95%) with high l/b ratios (up to 132.4) and excellent TON values (up to 23 760). The ZSM-5 and SO3H group of ligands improved the performances of hydroformylation and reductive amination.

Designing transparent piezoelectric metasurfaces for adaptive optics.

Simultaneously generating various motion modes with high strains in piezoelectric devices is highly desired for high-technology fields to achieve multi-functionalities. However, traditional approach for designing multi-degrees-of-freedom systems is to bond together several multilayer piezoelectric stacks, which generally leads to cumbersome and complicated structures. Here, we proposed a transparent piezo metasurface to achieve various types of strains in a wide frequency range. As an example, we designed a ten-unit piezo metasurface, which can produce high strains (ε3 = 0.76%), and generate linear motions along X-, Y- and Z-axis, rotary motions around X-, Y- and Z-axis as well as coupled modes. An adaptive lens based on the proposed piezo metasurface was demonstrated. It can realize a wide range of focal length (35.82 cm ~ ∞) and effective image stabilization with relatively large displacements (5.05 µm along Y-axis) and tilt angles (44.02' around Y-axis). This research may benefit the miniaturization and integration of multi-degrees-of-freedom systems.

A High-Q Electric-Mechano-Magnetic Coupled Resonator for ELF/SLF Cross-Medium Magnetic Communication.

Extremely/super low frequency (ELF/SLF) electromagnetic wave can effectively propagate in the harsh cross-medium environment where a high-frequency electromagnetic wave cannot pass due to the fast decay. For efficiently transmitting a strong ELF/SLF radiation signal, the traditional electromagnetic antenna requires a super-large loop (>10 km). To address this issue, in this work, a piezoelectric ceramic/ferromagnetic heterogeneous structured, cantilever beam-type electric-mechano-magnetic coupled resonator at only centimeter scale for ELF/SLF cross-medium magnetic communication is reported. Through designing hard-soft hybrid step-stiffness elastic beam, the resonator exhibits a much higher quality factor Q (≈240) for ELF/SLF magnetic field transmitting, which is one to five orders of magnitude higher than those of previously reported mechanical antennas and loop coil antennas. Moreover, the resonator exhibits a 5000 times higher magnetic field emitting efficiency compared to a conventional loop coil antenna in ELF/SLF band. It also demonstrates a 200% increase in magnetic field emitting capacity compared to existing piezoelectric-driven antennas. In addition, an ASK+PSK modulation method is proposed for suppressing relaxation time of the resonator, and a reduction in the relaxation time by 80% is observed. Furthermore, an air-seawater cross-medium magnetic field communication is successful demonstrated, indicating its potential as portable, high-efficient antenna for underwater and underground communications.

A Bionic Flapping Magnetic-Dipole Resonator for ELF Cross-Medium Communication.

Extremely low-frequency (ELF) electromagnetic (EM) waves adeptly propagate in harsh cross-medium environments, overcoming rapid decay that hinders high-frequency counterparts. Traditional antennas, however, encounter challenges concerning size, efficiency, and power. Here, drawing inspiration from nature, we present a groundbreaking piezo-actuated, bionic flapping-wing magnetic-dipole resonator (BFW-MDR), operating in the electro-mechano-magnetic coupling mechanism, designed for efficient ELF EM wave transmission. The unique rigid-flexible hybrid flapping-wing structure magnifies rotation angles of anti-phase magnetic dipoles by tenfold, leading to constructive superposition of emitted magnetic fields. Consequently, the BFW-MDR exhibits a remarkable quality factor of 288 and an enhanced magnetic field emission of 514 fT at 100 meters with only 6.9 mW power consumption, surpassing traditional coil antennas by three orders of magnitude. The communication rate is doubled by the ASK+PSK modulation method. Its robust performance in cross-medium communication, even amidst various interferences, underscores its potential as a highly efficient antenna for underwater and underground applications.

A Symmetric-Actuating Linear Piezoceramic Ultrasonic Motor Capable of Producing a Scissoring Effect.

Conventionally, to produce a linear motion, one motor's stator is employed to drive one runner moving forward or backward. So far, there is almost no report of one electromechanical motor or piezoelectric ultrasonic motor that can directly generate two symmetrical linear motions, while this function is desired for precise scissoring and grasping in the minimally invasive surgery field. Herein, we report a brand-new symmetric-actuating linear piezoceramic ultrasonic motor capable of generating symmetrical linear motions of two outputs directly without additional mechanical transmission mechanisms. The key component of the motor is an (2 × 3) arrayed piezoceramic bar stator operating in the coupled resonant mode of the first longitudinal (L1) and third bending (B3) modes, leading to symmetric elliptical vibration trajectories at its two ends. A pair of microsurgical scissors is used as the end-effector, demonstrating a very promising future for high-precision microsurgical operations. The sliders of the prototype show the following features: (a) symmetrical, fast relative moving velocity (~1 m/s) outward or inward simultaneously; (b) high step resolution (40 nm); and (c) high power density (405.4 mW/cm3) and high efficiency (22.1%) that are double those of typical piezoceramic ultrasonic motors, indicating the full capacity of symmetric-actuating linear piezoceramic ultrasonic motor working in symmetric operation principle. This work also has enlightening significance for future symmetric-actuating device designs.

Kirigami-Origami-Inspired Lead-Free Piezoelectric Ceramics.

Kirigami- and oirigami-inspired techniques have emerged as effective strategies for material structure design; however, the use of these techniques is usually limited to soft and deformable materials. Piezoelectric ceramics, which are typical functional ceramics, are widely used in electronic and energy devices; however, the processing options for piezoelectric ceramics are limited by their brittleness and feedstock viscosity. Here, a design strategy is proposed for the preparation of lead-free piezoelectric ceramics inspired by kirigami/origami. This strategy involves direct writing printing and control over the external gravity during the calcination process for the preparation of curved and porous piezoelectric ceramics with specific shapes. The sintered BaTiO3 ceramics with curved geometries produced using this strategy exhibit a high piezoelectric constant (d33 = 275 pC N-1 ), which is 45% higher than that of conventionally sintered sheet ceramics. The curved structure of the ceramics is well-suited for use in the human body and it was determined that these curved ceramics can detect pulse signals. This strategy can be applied in the large-scale and low-cost production of other piezoelectric ceramics with various curved shapes and provides a new approach for the preparation of complex-shaped ceramics.

A Multilayered Magnetoelectric Transmitter with Suppressed Nonlinearity for Portable VLF Communication.

Acoustically actuated magnetoelectric (ME) antenna based on the efficient oscillation of magnetic dipoles has recently been considered as a promising solution for portable very-low-frequency communications. However, the severe nonlinear dynamic behavior in the case of strong-field excitation results in insufficient radiation capability and poor communication performance for a conventional ME antenna. In this work, we propose to suppress the nonlinearity of an ME antenna by neutralizing the spring-hardening effect in amorphous Metglas and the spring-softening effect in piezoelectric ceramics through an ME multilayered transmitter (ME-MLTx) design. With a driving voltage of 50 Vpp at the resonance frequency of 21.2 kHz, a magnetic flux density as high as 108 fT at a distance of 100 m is produced from a single ME-MLTx. In addition, ME-MLTx performs a decreased mechanical quality factor (Q m) less than 40.65, and, thus, a broadened bandwidth of 500 Hz is generated. Finally, a communication link transmitting binary American Standard Code for Information Interchange-coded message is built, which allows for an error-free communication with a distance of 18 m and a data rate of 300 bit/s in the presence of heavy environment noise. The communication distance can be further estimated over 100 m when using a femtotesla-class-inductive magnetic field receiver. The obtained results are believed to bring ME antennas one step closer to being applicable in very-low-frequency communications.

Designing Artificial Vibration Modes of Piezoelectric Devices Using Programmable, 3D Ordered Structure with Piezoceramic Strain Units.

Piezoelectric ceramic devices, which utilize multifarious vibration modes to realize electromechanical coupling and energy conversions, are extensively used in high-technological fields. However, the excitation of basic modes is mainly subjected to natural eigenfrequency of ceramic devices, which is related to the structure and material parameters. Herein, inspired by metamaterial theory, a programmable, 3D ordered structure with piezoceramic strain units (3D OSPSU) is developed to artificially generate basic modes in a broad frequency band other than only in narrow eigenfrequency. A (2 × 2 × 2) arrayed, co-fired, multilayer 3D OSPSU is painstakingly designed and fabricated for generating basic modes, such as flexural, extension, shear, torsion, and even coupled modes at nonresonance. To validate the 3D OSPSU method, a five-degree-of-freedom micro-nano actuating platform based on only one co-fired multilayer ceramic is constructed. The proposed methodology provides a new paradigm for creating extraordinary material properties of piezoelectric ceramics and will inspire brand-new piezoelectric device designs.

Review on Piezoelectric Actuators Based on High-Performance Piezoelectric Materials.

The piezoelectric actuator is a kind of actuation device that acts through the inverse piezoelectric effect. Due to advantages of high precision, low power consumption, compact size, and flexible structure design, they have a wide range of applications in optics, robotics, microelectromechanical systems, and so on. Piezoelectric materials are the core materials for piezoelectric actuators. In this review, recent developments in high-performance piezoelectric materials (HPMs) are introduced, including relaxor ferroelectric crystals, textured ceramics, piezoelectric metamaterials, and so on. The advances of piezoelectric actuators are introduced in this review based on the developments of those piezoelectric materials, where the relationship between the figure of merits of materials and the performance of actuators is also discussed. Finally, we present outlooks and challenges for piezoelectric materials and actuators.

Miniaturized electromechanical devices with multi-vibration modes achieved by orderly stacked structure with piezoelectric strain units.

Piezoelectric devices based on a variety of vibration modes are widely utilized in high-tech fields to make a conversion between mechanical and electrical energies. The excitation of single or coupled vibration modes of piezoelectric devices is mainly related to the structure and property of piezoelectric materials. However, for the generally used piezoelectric materials, e.g., lead zirconate titanate ceramics, most of piezoelectric coefficients in the piezoelectric matrix are equal to zero, resulting in many piezoelectric vibration modes cannot be excited, which hinders the design of piezoelectric devices. In this work, an orderly stacked structure with piezoelectric strain units is proposed to achieve all nonzero piezoelectric coefficients, and consequently generate artificially coupled multi-vibration modes with ultrahigh strains. As an example, an orderly stacked structure with two piezoelectric strain units stator, corresponding to 31-36 coupled vibration mode, was designed and fabricated. Based on this orderly stacked structure with two piezoelectric strain units stator, we made a miniature ultrasonic motor (5 mmLength × 1.3 mmHeight × 1.06 mmWidth). Due to the ultrahigh strain of the 31-36 coupled vibration mode, the velocity per volume of the motor reached 4.66 s-1 mm-2. Furthermore, its moving resolution is around 3 nm, which is two orders higher than that of other piezoelectric motors. This work sheds a light on optimizing the performance of state-of-the-art electromechanical devices and may inspire new devices based on multi-vibration modes.

Designing Ordered Structure with Piezoceramic Actuation Units (OSPAU) for Generating Continual Nanostep Motion.

Continual precision actuations with nanoscale resolution over large ranges have extensive requirements in advanced intelligent manufacturing and precise surgical robots. To produce continual nanostep motion, conventionally, multiple pairs of piezo-actuators are employed to operate in inchworm principle under complex three- or four-phase timing signal drive. Inspired by the idea of ordered structures with functional units, a much simpler nanostep piezoelectric actuator consisting of (2 × 2) arrayed, cofired multilayer piezoceramic actuation units is developed, which operates in an artificially generated quasi shear mode (AGQSM) that is missing in natural piezoelectric ceramics. Under only one-phase square-wave voltage drive, the actuator can produce a stable, continual nanostep motion in two ways at nonresonant frequencies, and the obtained minimum step displacement is as low as 7 nm in open control, indicating its potential application as a precise finger or knife actuator in surgical robots. This work is of great guiding significance for future actuator designs using the methodology of ordered structure with piezoceramic actuation units and AGQSM.

Tailoring Artificial Mode to Enable Cofired Integration of Shear-type Piezoelectric Devices.

Low-temperature cofired ceramic technology is the prerequisite for producing advanced integrated piezoelectric devices that enable modern micro-electromechanical systems because of merits such as high level of compactness and ultralow drive voltage. However, piezoceramic structure with shear-type outputs, as a most fundamental functional electronic element, has never been successfully fabricated into multilayer form by the cofired method for decades. Technical manufacture requirements of parallel applied electric fields and polarization are theoretically incompatible with intrinsically orthogonal orientations in naturally occurring shear modes. Herein, inspired by the philosophy of building metamaterial from identical unit cells, an artificial prototype device with distinctive patterned electrodes and arrayed piezoceramic subunits is designed and fabricated, which is proved to perfectly generate synthetic face shear deformation. At the same drive voltage, an enhanced shear-type displacement output by over an order of magnitude is observed beyond previous d15-mode bulk elements. Further results of guided wave-based structural health monitoring and force sensing confirm that the methodology wipes out a tough piezoelectric technique barrier, and promises to fundamentally enlighten advances of integrated shear-mode piezoelectric devices for augmented actuation, sensing, and transduction applications.

Multifunctional Polymeric Prodrug with Simultaneous Conjugating Camptothecin and Doxorubicin for pH/Reduction Dual-Responsive Drug Delivery.

Amphiphilic polymeric prodrugs show improved therapeutic indices with respect to traditional hydrophobic anticancer drugs because these prodrugs can self-assemble into nanoparticles, prolong the circulation of drugs in the blood, improve the accumulation of drugs in the disease site, reduce the side effects of drugs, and achieve therapeutic effect. Here, we describe a novel pH/reduction dual-responsive polymeric prodrug, abbreviated as CPT- ss-poly(BYP- hyd-DOX- co-EEP), with simultaneous conjugating camptothecin (CPT) and doxorubicin (DOX), wherein BYP and EEP represent two cyclic phosphate monomers, respectively, that is, 2-(but-3-yn-1-yloxy)-2-oxo-1,3,2-dioxaphospholane and 2-ethoxy-2-oxo-1,3,2-dioxaphospholane. This prodrug was prepared through a polyphosphoester-DOX conjugate using a CPT derivative (CPT- ss-OH) as the initiator. CPT is linked to the terminal of polyphosphoester via disulfide carbonate, which is easy to break up under intracellular reductive environment and release the parent CPT, whereas DOX was efficiently incorporated onto the pendants of polyphosphoester through a hydrazone bond (- hyd-), which would be cleaved in the intracellular acidic medium. We show that the stable prodrug nanoparticles formed by self-assembly could release CPT and DOX simultaneously in the tumor microenvironment. The results of MTT assay demonstrate that the prodrug, which binds two antitumor drugs simultaneouly, has the properties of dual pH/reduction sensitiveness, biocompatibility, biodegradability, and effective tumor therapy.

A Piezoelectric and Electromagnetic Dual Mechanism Multimodal Linear Actuator for Generating Macro- and Nanomotion.

Fast actuation with nanoprecision over a large range has been a challenge in advanced intelligent manufacturing like lithography mask aligner. Traditional stacked stage method works effectively only in a local, limited range, and vibration coupling is also challenging. Here, we design a dual mechanism multimodal linear actuator (DMMLA) consisted of piezoelectric and electromagnetic costator and coslider for producing macro-, micro-, and nanomotion, respectively. A DMMLA prototype is fabricated, and each working mode is validated separately, confirming its fast motion (0~50 mm/s) in macromotion mode, micromotion (0~135 µm/s) and nanomotion (minimum step: 0~2 nm) in piezoelectric step and servomotion modes. The proposed dual mechanism design and multimodal motion method pave the way for next generation high-precision actuator development.

Designing electromechanical metamaterial with full nonzero piezoelectric coefficients.

Designing topological and geometrical structures with extended unnatural parameters (negative, near-zero, ultrahigh, or tunable) and counterintuitive properties is a big challenge in the field of metamaterials, especially for relatively unexplored materials with multiphysics coupling effects. For natural piezoelectric ceramics, only five nonzero elements in the piezoelectric matrix exist, which has impeded the design and application of piezoelectric devices for decades. Here, we introduce a methodology, inspired by quasi-symmetry breaking, realizing artificial anisotropy by metamaterial design to excite all the nonzero elements in contrast to zero values in natural materials. By elaborately programming topological structures and geometrical dimensions of the unit elements, we demonstrate, theoretically and experimentally, that tunable nonzero or ultrahigh values of overall effective piezoelectric coefficients can be obtained. While this work focuses on generating piezoelectric parameters of ceramics, the design principle should be inspirational to create unnatural apparent properties of other multiphysics coupling metamaterials.

Low-Temperature Co-Fired Unipoled Multilayer Piezoelectric Transformers.

The reliability of piezoelectric transformers (PTs) is dependent upon the quality of fabrication technique as any heterogeneity, prestress, or misalignment can lead to spurious response. In this paper, unipoled multilayer PTs were investigated focusing on high-power composition and co-firing profile in order to provide low-temperature synthesized high-quality device measured in terms of efficiency and power density. The addition of 0.2 wt% CuO into Pb0.98Sr0.02(Mg1/3Nb2/3)0.06(Mn1/3Nb2/3)0.06(Zr0.48Ti0.52)0.88O3 (PMMnN-PZT) reduces the co-firing temperature from 1240 °C to 930 °C, which allows the use of Ag/Pd inner electrode instead of noble Pt inner electrode. Low-temperature synthesized material was found to exhibit excellent piezoelectric properties ( , , %, pC/N, and °C). The performance of the PT co-fired with Ag/Pd electrode at 930 °C was similar to that co-fired at 1240 °C with Pt electrode (25% reduction in sintering temperature). Both high- and low-temperature synthesized PTs demonstrated 5-W output power with >90% efficiency and 11.5 W/cm3 power density.

Analytical solutions for the transverse deflection of a piezoelectric circular axisymmetric unimorph actuator.

This paper presents analytical solutions to the transverse deformation shape of a circular axisymmetric piezoelectric-metal composite unimorph actuator. The solutions account for both the influence of an applied electric field and a concentrated or uniformly distributed mechanical load. Using piezoelectric constitutive equations, combined with thin plate and small bending elastic theory, the generalized equation of motion for bending of thin piezoelectric-metal composite plates has been derived. Our approach predicts that there is an optimum thickness ratio between the piezoelectric and metal plates, which leads to a maximum combination of deflection and load carrying capabilities. Derived formulas are very simple that offer a quick method for engineering design and optimization of a circular unimorph piezoelectric actuator.

A micromachined piezoelectric microgripper for manipulation of micro/nanomaterials.

Micro/nanomaterials and devices have attracted great interest in recent years because of their extensive application prospects in almost all kinds of fields. However, the manipulations of the material at the micro/nanoscale, such as the separation or transfer of a micro/nano-object in the process of assembling micro/nanodevices, are quite difficult. In this paper, we present a micromachined micro-gripper made of photoresist material (SU-8) and driven by piezoelectric Pb(Mg,Nb)O3-PbTiO3 single crystal pieces. In order to keep two grasping jaws of the micro-gripper operating in the same plane at the micro/nanometer scale, a fine circular flexure hinge was fabricated for elastically connecting them together. After introducing the interface effect, the relationship between the opening stroke of two jaws and the applied voltage was developed and then confirmed by finite element simulation. The micro-gripper was finally installed on a six degree of freedom stage for performing a pick-up, release, and transfer manipulation of a 2 µm ZnO micro-fiber. The presented piezoelectric micro-gripper shows a great potential for the precise manipulation of a single piece of micro/nanomaterial for micro/nanodevices' assembling.

Enhanced Resonance Magnetoelectric Coupling in (1-1) Connectivity Composites.

Bulk-magnetoelectric (ME) composites consisting of various piezoelectric and piezomagnetic materials with (3-0), (3-1), (2-2), and (2-1) connectivity are proposed in a bid to realize strong ME coupling for next-generation electronic-device applications. Here, 1D (1-1) connectivity ME composites consisting of a [011]-oriented Pb(Mg,Nb)O3 -PbTiO3 (PMN-PT) single-crystal fiber laminated with laser-treated amorphous FeBSi alloy (Metglas) and operating in L-T mode (longitudinally magnetized and transversely poled) are reported, which exhibit an enhanced resonant ME coupling coefficient of ≈7000 V cm-1  Oe-1 , which is nearly seven times higher than the best result published previously, and also a superhigh magnetic sensitivity of 1.35 × 10-13 T (directly detected) at resonance at room temperature, representing a significant advance in bulk magnetoelectric materials. The theoretical analyses based on magnetic-circuit and equivalent-circuit methods show that the enhancement in ME coupling can be attributed to the reduction in resonance loss of laser-treated Metglas alloy due to nanocrystallization and the strong magnetic-flux-concentration effect in (1-1) configuration composites.