A light-activated polymer with excellent serum tolerance for intracellular protein delivery.

The design of efficient materials for intracellular protein delivery has attracted great interest in recent years; however, most current materials for this purpose are limited by poor serum stability due to the early release of cargoes triggered by abundant serum proteins. Here, we propose a light-activated crosslinking (LAC) strategy to prepare efficient polymers with excellent serum tolerance for intracellular protein delivery. A cationic dendrimer engineered with photoactivatable O-nitrobenzene moieties co-assembles with cargo proteins via ionic interactions, followed by light activation to yield aldehyde groups on the dendrimer and the formation of imine bonds with cargo proteins. The light-activated complexes show high stability in buffer and serum solutions, but dis-assemble under low pH conditions. As a result, the polymer successfully delivers cargo proteins green fluorescent protein and ß-galactosidase into cells with maintained bioactivity even in the presence of 50% serum. The LAC strategy proposed in this study provides a new insight to improve the serum stability of polymers for intracellular protein delivery.

Efficient intracellular and in vivo delivery of toxin proteins by a ROS-responsive polymer for cancer therapy.

Rational design of efficient cytosolic protein delivery carriers holds enormous promise for biotherapeutics development. Several delivery systems have been developed during the past decades, while tailoring the balance between extracellular protein binding and intracellular cargo release is still challenging. In this study, we synthesized a series of oxygen-sensitive reactive polymers, rich in boron, by radical polymerization and post-modification for cytosolic protein delivery in vitro and in vivo. The introduction of boronate building blocks into the polymer scaffold significantly enhanced its protein binding affinity, and the polymer/protein complexes with high stability were obtained by tailoring the molecular ratios between the boronate ligands and the amine groups. The lead material screened from the polymer library exhibited efficient protein delivery efficacy that can release cargo proteins in cytosol in a reactive oxygen species responsive manner, which enables intracellular delivery of proteins with maintained bioactivity. In addition, the polymer-based nanoformulations efficiently delivered saporin, a toxin protein, into osteosarcoma cells and tumor tissues, and exhibited high therapeutic efficacy in an osteosarcoma mouse model. The synthesized polymer in this study can be developed as a promising nanocarrier for cytosolic delivery of protein therapeutics to treat a variety of diseases.

Research on Performance Optimization and Application in Smart Home for Hyperledger Fabric.

With the popularity of smart home services, smart home devices are also increasing significantly. At the same time, security problems of smart home services are becoming more and more important. With the characteristics of non-tampering and multi-party consensus mechanism, Blockchain technology provides powerful capabilities in security protection. In this paper, we introduce the widely used permission Blockchain Fabric for smart home services. As the high requirements of performance, we firstly study the methods of performance optimization for Fabric. Then, a Fabric-based smart home security control system is designed. Based on this system, the smart home system is able to provide access control and security control for smart home devices. The experimental results show that the system works best when the number of concurrent registrations of smart home device is under 6000.

Amphipathic poly-ß-peptides for intracellular protein delivery.

A series of amphipathic poly-ß-peptides are designed for intracellular protein delivery. The poly-ß-peptides with higher molecular weight and hydrophobic contents exhibit higher protein loading and superior delivery efficiency. The lead material efficiently delivers proteins into cells with reserved bioactivity.

A manganese (II)-based coordinative dendrimer with robust efficiency in intracellular peptide delivery.

Peptides have gained increasing interests as drug candidates in modern pharmaceutical industry, however, the development of peptide drugs acting on intracellular targets is limited due to their membrane impermeability. Here, we reported the use of metal-terpyridine based coordinative dendrimer for cytosolic peptide delivery. Among the investigated transition metal ions, Mn2+-coordinated polymer showed the highest delivery efficiency due to balanced peptide binding and release. It showed robust efficiency in the delivery of peptides with different charge property and hydrophobicity into various primary cells. The efficiency of Mn2+-terpyridine based polymer is superior to cell penetrating peptides such as oligoarginines. The material also delivered an autophagy-inducing peptide derived from Beclin-1 into cells and efficiently induced autophagy in the cells. This study provides a promising alternative to cell penetrating peptides for cytosolic peptide delivery.

A Coordinative Dendrimer Achieves Excellent Efficiency in Cytosolic Protein and Peptide Delivery.

Cytosolic protein delivery is a prerequisite for the development of protein therapeutics that act on intracellular targets. Proteins are generally membrane-impermeable and thus need a carrier such as a polymer to facilitate their internalization. However, the efficient binding of proteins with different isoelectric points to polymeric carriers is challenging. In this study, we designed a coordinative dendrimer to solve this problem. The dendrimers modified with dipicolylamine/zinc(II) complex were capable of binding proteins through a combination of ionic and coordination interactions. The best polymer efficiently delivered 30 cargo proteins and peptides into the cytosol, while maintaining their bioactivity after intracellular release. The removal or replacement of zinc ions in the polymer with other transition-metal ions lead to significantly decreased efficiency in cytosolic protein delivery. This study provides a new strategy to develop robust and efficient polymers for cytosolic protein delivery.

"All-in-One" Theranostic Agent with Seven Functions Based on Bi-Doped Metal Chalcogenide Nanoflowers.

Most of the existing single-component nanostructures cannot provide comprehensive diagnostic information, and their treatment strategies always have to combine other therapeutics as a complementary for effective biomedical application. Here, we adopted a facile approach to design a theranostic nanoflower (NF) with robust efficacy for comprehensive tumor diagnosis and quadruple synergistic cancer therapy. The NF is equipped with a metallic hybrid of several functional elements and flower-like superstructures and thus shows excellent in vitro and in vivo theranostic performance. It shows high X-ray attenuation coefficiency for the Bi element, strong near-infrared (NIR) plasmon absorbance and singlet oxygen (1O2) generation ability for the Mo element, and great photothermal conversion efficiency (54.7%) because of enhanced photoabsorption of the petal structure. Moreover, the NF realizes a very high doxorubicin-loading efficiency (90.0%) and bimodal pH/NIR-responsive drug release, posing a promise as a controlled drug carrier. The NF also shows excellent performance at trimodal magnetic resonance/X-ray computed tomography/photoacoustic imaging for comprehensive tumor diagnosis. To our best knowledge, it is the first time that integrating at least seven functions into one biomedical nanomaterial for well-rounded tumor theranostics has been reported. This "all-in-one" NF opens a new perspective in developing novel and efficient multifunctional nanotheranostics.

Facile fabrication of a magnetically smart PTX-loaded Cys-Fe3O4/CuS@BSA nano-drug for imaging-guided chemo-photothermal therapy.

In this study, a multifunctional nano-drug (PTX-loaded Cys-Fe3O4/CuS@BSA nanocomposite), which performs well in hydrophobic drug delivery, magnetic resonance imaging (MRI) and chemo-photothermal combination therapy, has been successfully synthesized via a facile method with several biocompatible agents. The characterization verified that our as-obtained nanocarrier has a preferable average diameter of about 300 nm for cancer therapy, shows a great MRI ability and magnetism performance, and exhibits a favorable in vitro and in vivo photothermal therapeutic efficacy by introducing CuS, and the sustained release of chemotherapeutics could be controlled by pH value and near-infrared laser irradiation has further enhanced the therapeutic performance. Overall, the excellent synergistic effect to inhibit tumor growth effectively realized via imaging-guided combinational chemo-photothermal therapy in the present work, highlights the promise of conquering the limitations of tumor treatments.

Sex- and season-dependent differences in telomere length and telomerase activity in the leaves of ash and willow.

Telomeres and telomerase have important biological functions and can protect chromosome ends. In this study, sex- and season-dependent changes in telomere length and telomerase activity in ash and willow were analyzed. A statistical analysis showed that the telomere lengths of male and female trees differed significantly (P < 0.05). In ash, the telomere lengths of female trees were shorter than those of male trees. In willow, the telomere lengths of female trees were longer than those of male trees. During the annual developmental cycle, the telomere lengths of male and female ash and willow increased from April to May (P < 0.05), remained stable from May to August (P > 0.05), and decreased significantly in September and October (P < 0.05). Additionally, telomerase activities could be detected in both male and female ash and willow trees from April to October. Our results show that the telomere lengths changed according to season and sex in ash and willow. Telomere length did not have a direct positive correlation with telomerase activity.