Activation of the Catalytic Activity of Thrombin for Fibrin Formation by Ultrasound

The regulation of enzyme activity is a method to control biological function. We report two systems enabling the ultrasound-induced activation of thrombin, which is vital for secondary hemostasis. First, we designed polyaptamers, which can specifically bind to thrombin, inhibiting its catalytic activity. With ultrasound generating inertial cavitation and therapeutic medical focused ultrasound, the interactions between polyaptamer and enzyme are cleaved, restoring the activity to catalyze the conversion of fibrinogen into fibrin. Second, we used split aptamers conjugated to the surface of gold nanoparticles (AuNPs). In the presence of thrombin, these assemble into an aptamer tertiary structure, induce AuNP aggregation, and deactivate the enzyme. By ultrasonication, the AuNP aggregates reversibly disassemble releasing and activating the enzyme. We envision that this approach will be a blueprint to control the function of other proteins by mechanical stimuli in the sonogenetics field. © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH Gmb

Activation of the Catalytic Activity of Thrombin for Fibrin Formation by Ultrasound

The regulation of enzyme activity is a method to control biological function. We report two systems enabling the ultrasound-induced activation of thrombin, which is vital for secondary hemostasis. First, we designed polyaptamers, which can specifically bind to thrombin, inhibiting its catalytic activity. With ultrasound generating inertial cavitation and therapeutic medical focused ultrasound, the interactions between polyaptamer and enzyme are cleaved, restoring the activity to catalyze the conversion of fibrinogen into fibrin. Second, we used split aptamers conjugated to the surface of gold nanoparticles (AuNPs). In the presence of thrombin, these assemble into an aptamer tertiary structure, induce AuNP aggregation, and deactivate the enzyme. By ultrasonication, the AuNP aggregates reversibly disassemble releasing and activating the enzyme. We envision that this approach will be a blueprint to control the function of other proteins by mechanical stimuli in the sonogenetics field

Anticancer drug nanomicelles formed by self-assembling amphiphilic dendrimer to combat cancer drug resistance

Drug resistance and toxicity constitute challenging hurdles for cancer therapy. The application of nanotechnology for anticancer drug delivery is expected to address these issues and bring new hope for cancer treatment. In this context, we established an original nanomicellar drug delivery system based on an amphiphilic dendrimer (AmDM), which could generate supramolecular micelles to effectively encapsulate the anticancer drug doxorubicin (DOX) with high drug-loading capacity (>40%), thanks to the unique dendritic structure creating large void space for drug accommodation. The resulting AmDM/DOX nanomicelles were able to enhance drug potency and combat doxorubicin resistance in breast cancer models by significantly enhancing cellular uptake while considerably decreasing efflux of the drug. In addition, the AmDM/DOX nanoparticles abolished significantly the toxicity related to the free drug. Collectively, our studies demonstrate that the drug delivery system based on nanomicelles formed with the self-assembling amphiphilic dendrimer constitutes a promising and effective drug carrier in cancer therapy

Activation of the Catalytic Activity of Thrombin for Fibrin Formation by Ultrasound

The regulation of enzyme activity is a method to control biological function. We report two systems enabling the ultrasound-induced activation of thrombin, which is vital for secondary hemostasis. First, we designed polyaptamers, which can specifically bind to thrombin, inhibiting its catalytic activity. With ultrasound generating inertial cavitation and therapeutic medical focused ultrasound, the interactions between polyaptamer and enzyme are cleaved, restoring the activity to catalyze the conversion of fibrinogen into fibrin. Second, we used split aptamers conjugated to the surface of gold nanoparticles (AuNPs). In the presence of thrombin, these assemble into an aptamer tertiary structure, induce AuNP aggregation, and deactivate the enzyme. By ultrasonication, the AuNP aggregates reversibly disassemble releasing and activating the enzyme. We envision that this approach will be a blueprint to control the function of other proteins by mechanical stimuli in the sonogenetics field.</p

A High-Capacity Optical Metro Access Network: Efficiently Recovering Fiber Failures with Robust Switching and Centralized Optical Line Terminal

This study proposes and presents a new central office (CO) for the optical metro access network (OMAN) with an affordable and distinctive switching system. The CO’s foundation is built upon a novel optical multicarrier (OMC) generation technique. This technique provides numerous frequency carriers that are characterized by a high tone-to-noise ratio (TNR) of 40 dB and minimal amplitude excursions. The purpose is to accommodate multiple users at the optical network unit side in the optical metropolitan area network (OMAN). The OMC generation is achieved through a cascaded configuration involving a single phase and two Mach Zehnder modulators without incorporating optical or electrical amplifiers or filters. The proposed OMC is installed in the CO of the OMAN to support the 1.2 Tbps downlink and 600 Gbps uplink transmission, with practical bit error rate (BER) ranges from 10−3 to 10−13 for the downlink and 10−6 to 10−14 for the uplink transmission. Furthermore, in the OMAN’s context, optical fiber failure is a main issue. Therefore, we have proposed a possible solution for ensuring uninterrupted communication without any disturbance in various scenarios of main optical fiber failures. This demonstrates how this novel CO can rapidly recover transmission failures through robust switching a and centralized OLT. The proposed system is intended to provide users with a reliable and affordable service while maintaining high-quality transmission rates

Electrical tunable topological valley photonic crystals for on-chip optical communications in the telecom band

On-chip optical communications are in increasingly demand for low-loss, small-footprint and power-efficient waveguiding solutions in the telecom band. However, most integrated optical circuits suffer from high propagation loss and low integration degree. Through manipulating the valley-dependent topological phase of light, we have experimentally demonstrated both robust optical transport and electrical modulation of lightwaves at telecom wavelengths in the valley photonic crystals. With the adoption of valley kink states, the 25 Gbit/s optical signal at 1550 nm is successfully transmitted through a highly twisted interface. Furthermore, an extreme high data rate of 100 Gbit/s is demonstrated with such topological waveguide by wavelength division multiplexing. The electrical tunability of the topological modulators based on thermo-optic effect is also verified, opening a novel route towards active valley kink photonic devices. Our study shows a great possibility of making use of the topological protection in building up high-speed datalinks on a chip.Published versionThis work was supported by the Innovation and Entrepreneurship Program of Jiangsu Province (JSSCBS20210467), the Natural Science Foundation of the Jiangsu Higher Institution of China (21KJB140012), the Natural Science Foundation of Jiangsu Province (SBK2021041180), the National Natural Science Foundation of China (62105158, 62075038)

Probe-Inspired Nano-Prodrug with Dual-Color Fluorogenic Property Reveals Spatiotemporal Drug Release in Living Cells

The versatility of the fluorescent probes inspires us to design fluorescently traceable prodrugs, which enables tracking the drug delivery kinetics in living cells. Herein, we constructed a self-indicating nanoprodrug with two fluorescent moieties, an aggregation-induced emission molecule (tetraphenylethylene, TPE) and a luminant anticancer drug (doxorubicin, DOX), with a pH-responsive linker between them. Except when a low pH environment is encountered, an energy-transfer relay (ETR) occurs and inactivates the fluorescence of both, showing a dark background. Otherwise, the ETR would be interrupted and evoke a dual-color fluorogenic process, giving distinct fluorogenic read out. By observing the dual-color fluorogenic scenario, we captured the kinetics of the drug release process in living cells. Because the separated TPE and DOX are both fluorescent but have a distinct spectrum, by examining the spatiotemporal pattern of TPE and DOX, we were able to precisely disclose the drug-releasing site, the releasing time, the destinations of the carriers, and the executing site of the drugs at subcellular level. Furthermore, different intracellular drug release kinetics between free doxorubicin and its nanoformulations were also observed in a real-time manner

Ultrasmall Gold Nanoparticles Behavior in Vivo Modulated by Surface Polyethylene Glycol (PEG) Grafting

Ultrasmall nanoparticles provide us with essential alternatives for designing more efficient nanocarriers for drug delivery. However, the fast clearance of ultrasmall nanoparticles limits their application to some extent. One of the most frequently used compound to slow the clearance of nanocarriers and nanodrugs is PEG, which is also approved by FDA. Nonetheless, few reports explored the effect of the PEGylation of ultrasmall nanoparticles on their behavior in vivo. Herein, we investigated the impact of different PEG grafting level of 2 nm core sized gold nanoparticles on their biological behavior in tumor-bearing mice. The results indicate that partial (∼50%) surface PEGylation could prolong the blood circulation and increase the tumor accumulation of ultrasmall nanoparticles to a maximum extent, which guide us to build more profitable small-sized nanocarriers for drug delivery