A convenient protonated strategy for constructing nanodrugs from hydrophobic drug-inhibitor conjugates to reverse tumor multidrug resistance.

Combination therapy has proven effective in counteracting tumor multidrug resistance (MDR). However, the pharmacokinetic differences among various drugs and inherent water insolubility for most small molecule agents greatly hinder their synergistic effects, which makes the delivery of drugs for combination therapy in vivo a key problem. Herein, we propose a protonated strategy to transform a water-insoluble small molecule drug-inhibitor conjugate into an amphiphilic one, which then self-assembles into nanoparticles for co-delivery in vivo to overcome tumor MDR. Specifically, paclitaxel (PTX) is first coupled with a third-generation P-glycoprotein (P-gp) inhibitor zosuquidar (Zos) through a glutathione (GSH)-responsive disulfide bond to produce a hydrophobic drug-inhibitor conjugate (PTX-ss-Zos). Subsequently treated with hydrochloric acid ethanol solution (HCl/EtOH), PTX-ss-Zos is transformed into the amphiphilic protonated precursor and then forms nanoparticles (PTX-ss-Zos@HCl NPs) in water by molecular self-assembly. PTX-ss-Zos@HCl NPs can be administered intravenously and accumulated specifically at tumor sites. Once internalized by cancer cells, PTX-ss-Zos@HCl NPs can be degraded under the overexpressed GSH to release PTX and Zos simultaneously, which synergistically reverse tumor MDR and inhibit tumor growth. This offers a promising strategy to develop small molecule self-assembled nanoagents to reverse tumor MDR in combination therapy.

Hybrid Membrane Camouflaged Chemodrug-Gene Nanoparticles for Enhanced Combination Therapy of Ovarian Cancer.

Recently, cell membrane camouflaged nanoparticles (NPs) endowed with natural cellular functions have been extensively studied in various biomedical fields. However, there are few reports about such biomimetic NPs used to codeliver chemodrug and genes for synergistic cancer treatment up to now. Herein, we first prepare chemodrug-gene nanoparticles (Mito-Her2 NPs) by the electrostatic interaction coself-assembly of mitoxantrone hydrochloride (Mito) and human epidermal growth factor receptor-2 antisense oligonucleotide (Her2 ASO). Then, Mito-Her2 NPs are coated by a hybrid membrane (RSHM), consisting of the red blood cell membrane (RBCM) and the SKOV3 ovarian cancer cell membrane (SCM), to produce biomimetic chemodrug-gene nanoparticles (Mito-Her2@RSHM NPs) for combination therapy of ovarian cancer. Mito-Her2@RSHM NPs integrate the advantages of RBCM (e.g., good immune evasion capability and long circulation lifetime in the blood) and SCM (e.g., highly specific cognate recognition) together and improve the anticancer efficacy of Mito-Her2 NPs. The results show that Mito-Her2@RSHM NPs can be devoured by SKOV3 ovarian cancer cells and effectively degraded to release Her2 ASOs and Mito simultaneously. Her2 ASOs can inhibit the expression of endogenous Her2 genes and recover cancer cells' sensitivity to Mito, which ultimately led to a high apoptosis rate of 75.7% in vitro. Mito-Her2@RSHM NPs also show a high tumor suppression rate of 83.33 ± 4.16% in vivo without significant damage to normal tissues. In summary, Mito-Her2@RSHM NPs would be expected as a versatile and safe nanodrug delivery platform with high efficiency for chemo-gene combined cancer treatment.

Binary Electronic Synapses for Integrating Digital and Neuromorphic Computation in a Single Physical Platform.

As a promising advanced computation technology, the integration of digital computation with neuromorphic computation into a single physical platform holds the advantage of a precise, deterministic, fast data process as well as the advantage of a flexible, paralleled, fault-tolerant data process. Even though two-terminal memristive devices have been respectively proved as leading electronic elements for digital computation and neuromorphic computation, it is difficult to steadily maintain both sudden-state-change and gradual-state-change in a single device due to the entirely different operating mechanisms. In this work, we developed a digital-analog compatible memristive device, namely, binary electronic synapse, through realizing controllable cation drift in a memristive layer. The devices feature nonvolatile binary memory as well as artificial neuromorphic plasticity with high operation endurance. With strong nonlinearity in switching dynamics, binary switching, neuromorphic plasticity, two-dimension information store, and trainable memory can be implemented by a single device.

Nano-Ripple ZnO-Based Triboelectric Nanogenerator for Applications in Self-Powered Ultraviolet Detector.

Ultraviolet (UV) detectors have a wide range of commercial applications. However, most UV light detectors require an external power source, which limits their applications as portable and/or wearable electronics. In this work, a self-powered UV detector based on triboelectric nanogenerator (TENG) technology is demonstrated. Nano-ripple zinc oxide (ZnO) film acting as both UV-sensitive and triboelectric material was synthesized by a simple sol-gel method. The self-powered UV sensor detected UV irradiation without an external power source. The open-circuit voltage of the device under UV irradiation was 130 V, which was 2.3 times higher than the output of the device in the dark. Possible operating mechanisms of the device, which is based on the contact electrification process, are described.