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.

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.

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-sound-resonance cavity for hydrogen gas detection.

A new concept for hydrogen gas (H2) detection has been developed. This concept is based on a piezoelectric-sound-resonance cavity (PSRC). Detection uses sound resonance and the acoustic property differences of gases as a sensing mechanism in which there is a significant difference in the sound velocity and acoustic impedance between H2 and air. The PSRC sensor consists of two thin piezoelectric discs, separated by a small cavity. One disc excites a weak acoustic standing wave in the cavity, and the second senses the wave by monitoring the acoustic impedance characteristics of the cavity. Changes in H2 concentration result in a shift of the sound resonance state. Investigations of a PSRC prototype have demonstrated a sensitivity limit of <10 ppm, a fast response time approximately 1 second, and a signal (phase and voltage) in proportion to the change in H2 concentration (n) over the range of 10(-5) < n < 0.2. These performance characteristics are far superior to those of other methods.