Triterpene-Based Prodrug for Self-Boosted Drug Release and Targeted Oral Squamous Cell Carcinoma Chemotherapy.

Chemotherapy is one of the main treatments for oral squamous cell carcinoma (OSCC), especially as a combined modality approach with and after surgery or radiotherapy. Limited therapeutic efficiency and serious side effects greatly restrict the clinical performance of chemotherapeutic drugs. The development of smart nanomedicines has provided new research directions, to some extent. However, the involvement of complex carrier compositions inevitably brings biosafety concerns and greatly limits the "bench-to-bed" translation of most nanomedicines reported. In this study, a carrier-free self-assembled prodrug was fabricated by two triterpenes (glycyrrhetinic acid, GA and ginsenoside Rh2, Rh2) isolated from medicinal plants, licorice, and ginseng, for the targeted and highly effective treatment of OSCC. Reactive oxygen species (ROS) self-supplied molecule TK-GA2 was synthesized with ROS-responsive thioketal linker and prodrug was prepared by a rapid-solvent-exchange method with TK-GA2 and Rh2. After administration, oral tumor cells transported large amounts of prodrugs with glucose ligands competitively. Endogenous ROS in oral tumor cells then promoted the release of GA and Rh2. GA further evoked the generation of a large number of ROS to help self-boosted drug release and increase oxidative stress, synergistically causing tumor cell apoptosis with Rh2. Overall, this carrier-free triterpene-based prodrug might provide a preeminent opinion on the design of effective chemotherapeutics with low systemic toxicity against OSCC.

Traditional Chinese Medicine Formulae QY305 Reducing Cutaneous Adverse Reaction and Diarrhea by its Nanostructure.

Traditional Chinese medicine (TCM) is widely used in clinical practice, including skin and gastrointestinal diseases. Here, a potential TCM QY305 (T-QY305) is reported that can modulate the recruitment of neutrophil in skin and colon tissue thus reducing cutaneous adverse reaction and diarrhea induced by epidermal growth factor receptor inhibitors (EGFRIs). On another hand, the T-QY305 formula, through regulating neutrophil recruitment features would highlight the presence of N-QY305, a subunit nanostructure contained in T-QY305, and confirm its role as potentially being the biomaterial conferring to T-QY305 its pharmacodynamic features. Here, the clinical records of two patients are analyzed expressing cutaneous adverse reaction and demonstrate positive effect of T-QY305 on the simultaneous inhibition of both cutaneous adverse reaction and diarrhea in animal models. The satisfying results obtained from T-QY305, lead to further process to the isolation of N-QY305 from T-QY305, in order to demonstrate that the potency of T-QY305 originates from the nanostructure N-QY305. Compared to T-QY305, N-QY305 exhibits higher potency upon reducing adverse reactions. The data represent a promising candidate for reducing cutaneous adverse reaction and diarrhea, meanwhile proposing a new strategy to highlight the presence of nanostructures being the "King" of Chinese medicine formula as the pharmacodynamic basis.

DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild-Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression.

Patients with triple-negative breast cancer (TNBC) have the worst clinical outcomes when compared to other subtypes of breast cancer. Nanotechnology-assisted photothermal therapy (PTT) opens new opportunities for precise cancer treatment. However, thermoresistance caused by PTT, as well as uncertainty in the physiological metabolism of existing phototherapeutic nanoformulations, severely limit their clinical applications. Herein, based on the clinically chemotherapeutic drug mitoxantrone (MTO), a multifunctional nanoplatform (MTO-micelles) is developed to realize mutually synergistic mild-photothermal chemotherapy. MTO with excellent near-infrared absorption (≈669 nm) can function not only as a chemotherapeutic agent but also as a photothermal transduction agent with elevated photothermal conversion efficacy (ƞ = 54.62%). MTO-micelles can accumulate at the tumor site through the enhanced permeability and retention effect. Following local near-infrared irradiation, mild hyperthermia (<50 °C) assists MTO in binding tumor cell DNA, resulting in chemotherapeutic sensitization. In addition, downregulation of heat shock protein 70 (HSP70) expression due to enhanced DNA damage can in turn weaken tumor thermoresistance, boosting the efficacy of mild PTT. Both in vitro and in vivo studies indicate that MTO-micelles possess excellent synergetic tumor inhibition effects. Therefore, the mild-photothermal chemotherapy strategy based on MTO-micelles has a promising prospect in the clinical transformation of TNBC treatment.

Lipid-Based Intelligent Vehicle Capabilitized with Physical and Physiological Activation.

Intelligent drug delivery system based on "stimulus-response" mode emerging a promising perspective in next generation lipid-based nanoparticle. Here, we classify signal sources into physical and physiological stimulation according to their origin. The physical signals include temperature, ultrasound, and electromagnetic wave, while physiological signals involve pH, redox condition, and associated proteins. We first summarize external physical response from three main points about efficiency, particle state, and on-demand release. Afterwards, we describe how to design drug delivery using the physiological environment in vivo and present different current application methods. Lastly, we draw a vision of possible future development.

A New MEMS Gyroscope Used for Single-Channel Damping.

The silicon micromechanical gyroscope, which will be introduced in this paper, represents a novel MEMS gyroscope concept. It is used for the damping of a single-channel control system of rotating aircraft. It differs from common MEMS gyroscopes in that does not have a drive structure, itself, and only has a sense structure. It is installed on a rotating aircraft, and utilizes the aircraft spin to make its sensing element obtain angular momentum. When the aircraft is subjected to an angular rotation, a periodic Coriolis force is induced in the direction orthogonal to both the angular momentum and the angular velocity input axis. This novel MEMS gyroscope can thus sense angular velocity inputs. The output sensing signal is exactly an amplitude-modulation signal. Its envelope is proportional to the input angular velocity, and the carrier frequency corresponds to the spin frequency of the rotating aircraft, so the MEMS gyroscope can not only sense the transverse angular rotation of an aircraft, but also automatically change the carrier frequency over the change of spin frequency, making it very suitable for the damping of a single-channel control system of a rotating aircraft. In this paper, the motion equation of the MEMS gyroscope has been derived. Then, an analysis has been carried to solve the motion equation and dynamic parameters. Finally, an experimental validation has been done based on a precision three axis rate table. The correlation coefficients between the tested data and the theoretical values are 0.9969, 0.9872 and 0.9842, respectively. These results demonstrate that both the design and sensing mechanism are correct.

Measurement of phase difference for micromachined gyros driven by rotating aircraft.

This paper presents an approach for realizing a phase difference measurement of a new gyro. A silicon micromachined gyro was mounted on rotating aircraft for aircraft attitude control. Aircraft spin drives the silicon pendulum of a gyro rotating at a high speed so that it can sense the transverse angular velocity of the rotating aircraft based on the gyroscopic precession principle when the aircraft has transverse rotation. In applications of the rotating aircraft single channel control system, such as damping in the attitude stabilization loop, the gyro signal must be kept in sync with the control signal. Therefore, the phase difference between both signals needs to be measured accurately. Considering that phase difference is mainly produced by both the micromachined part and the signal conditioning circuit, a mathematical model has been established and analyzed to determine the gyro's phase frequency characteristics. On the basis of theoretical analysis, a dynamic simulation has been done for a case where the spin frequency is 15 Hz. Experimental results with the proposed measurement method applied to a silicon micromachined gyro driven by a rotating aircraft demonstrate that it is effective in practical applications. Measured curve and numerical analysis of phase frequency characteristic are in accordance, and the error between measurement and simulation is only 5.3%.

A micro-machined gyroscope for rotating aircraft.

In this paper we present recent work on the design, fabrication by silicon micromachining, and packaging of a new gyroscope for stabilizing the autopilot of rotating aircraft. It operates based on oscillation of the silicon pendulum between two torsion girders for detecting the Coriolis force. The oscillation of the pendulum is initiated by the rolling and deflecting motion of the rotating carrier. Therefore, the frequency and amplitude of the oscillation are proportional to the rolling frequency and deflecting angular rate of the rotating carrier, and are measured by the sensing electrodes. A modulated pulse with constant amplitude and unequal width is obtained by a linearizing process of the gyroscope output signal and used to control the deflection of the rotating aircraft. Experimental results show that the gyroscope has a resolution of 0.008 °/s and a bias of 56.18 °/h.

Design and implementation of a digital angular rate sensor.

With the aim of detecting the attitude of a rotating carrier, the paper presents a novel, digital angular rate sensor. The sensor consists of micro-sensing elements (gyroscope and accelerometer), signal processing circuit and micro-processor (DSP2812). The sensor has the feature of detecting three angular rates of a rotating carrier at the same time. The key techniques of the sensor, including sensing construction, sensing principles, and signal processing circuit design are presented. The test results show that the sensor can sense rolling, pitch and yaw angular rate at the same time and the measurement error of yaw (or pitch) angular rate and rolling rate of the rotating carrier is less than 0.5%.