Rational Design of Nanogels for Overcoming the Biological Barriers in Various Administration Routes.

Nanogels have been identified as outstanding nanocarrier candidates for drug delivery due to their desirable physiochemical properties and versatile applicability for diverse therapeutic molecules and imaging probes. One of the main challenges that hinder the clinical translation of nanogels is the low efficiency of drug delivery to the target sites because of the complex biological barriers during the in vivo journey. The purpose of this review is to examine and summarize the recent advances on the rational design and structural modulation of nanogels to overcome the barriers and challenges on the way to the site of action following various dosing modes. In particular, the functional moieties or domains have been incorporated in the nanogels, allowing them to spontaneously regulate their structure and physiochemical properties to cross one or more of the multifaceted barriers. In addition, the future perspectives are presented with regards to opportunities and challenges for the precise and efficient therapeutic use of nanogel formulations.

Bacterial toxicity of exfoliated black phosphorus nanosheets.

Newly emerged two-dimensional material, black phosphorus (BP) shows promising applications in many fields owing to its superior properties. Despite the biological effects of BP were studied, its environmental impacts have not yet received enough attention. In this study, the bacterial toxicity of exfoliated BP nanosheets was for the first time evaluated against two model bacteria strains, Gram-negative Escherichia coli (E. coli) and Gram-positive Bacillus subtilis (B. subtilis). By monitoring the bacterial growth curve and colony counting, the bacterial toxicity of BP nanosheets was examined. Higher toxicity was induced for Gram-negative E. coli compared to Gram-positive B. subtilis after 6 h treatment, which was reversed at 12 h due to membrane self-healing of E. coli. The bacterial toxicity followed a time- and concentration-dependent fashion, with a maximum bactericidal efficiency of 91.65% and 99.69% for E. coli and B. subtilis, respectively, after 12 h exposure. Reactive oxygen species (ROS)-dependent oxidative stress and membrane damage were the main bactericidal mechanisms as proved by fluorescence microscopy, flow cytometry, scanning electron microscopy (SEM), and Lactate dehydrogenase (LDH) assay. This study indicates the potential environmental risk of BP nanosheets and the data from this work will guide their safety applications in the future.

Size Effect on the Cytotoxicity of Layered Black Phosphorus and Underlying Mechanisms.

A systematic cytotoxicity study of layered black phosphorus (BP) is urgently needed before moving forward to its potential biomedical applications. Herein, bulk BP crystals are synthesized and exfoliated into layered BP with different lateral size and thickness. The cytotoxicity of as-exfoliated layered BP is evaluated by a label-free real-time cell analysis technique, displaying a concentration-, size-, and cell type-dependent response. The IC50 values can vary by 40 and 30 times among the BP sizes and cell types, respectively. BP-1 with the largest lateral size and thickness has the highest cytotoxicity; whereas the smallest BP-3 only shows moderate toxicity. The sensitivity of three tested cell lines follows the sequence of 293T > NIH 3T3 > HCoEpiC. Two possible mechanisms for BP to induce cytotoxicity are proposed and verified: (1) the generation of intracellular reactive oxygen species (ROS) is detected by a ROS sensitive probe using the inverted fluorescence microscopy and flow cytometry; (2) the interaction of layered BP and model cell membrane is examined by quartz crystal microbalance with dissipation, illustrating the disruption of cell membrane integrity especially by the largest BP-1. This systematic study of BP's cytotoxicity will shed light on its future biomedical and environmental applications.

A Patent Analysis on Nano Drug Delivery Systems.

BACKGROUND: A nano drug delivery system is an effective tool for drug delivery and controlled release, which is used for a variety of medical applications. In recent decades, nano drug delivery systems have been significantly developed with the emergence of new nanomaterials and nanotechnologies. OBJECTIVE: This article aimed to provide insight into the technological development of nano drug delivery systems through patent analysis. METHODS: 3708 patent documents were used for patent analysis after retrieval from the Incopat patent database. RESULTS: The number of patents on nano drug delivery systems has shown a rapid growth trend in the past two decades. At present, China and the United States have obvious contributions to the number of patents. According to the patent data, the nanomaterials used in nano drug delivery system are mainly inorganic nanomaterials, lipid-based nanomaterials, and macromolecules. In recent years, the highly cited patents (≥14) for nano drug delivery systems mainly involve lipid-based nanomaterials, indicating that their technology is mature and widely used. The inorganic nanomaterials in drug delivery have received increasing attention, and the number of related patents has increased significantly after 2016. The number of highly cited patents in the United States is 250, which is much higher than in other countries. CONCLUSION: Even after decades of development, nano drug delivery systems remain a hot topic for researchers. The significant increase in patents since 2016 can be attributed to the large number of new patents from China. However, according to the proportion of highly cited patents in total, China's patented technologies in nano drug delivery systems are not advanced enough compared to developed countries, including the United States, Canada, Germany, and France. In the future, research on emerging nanomaterials for nano drug delivery systems, such as inorganic nanomaterials, may focus on developing new materials and optimising their properties. The lipid-based and polymer- based nanomaterials can be continuously improved for the development of new nanomedicines.

Reprogramming the Metabolism of Yeast for High-Level Production of Miltiradiene.

Miltiradiene serves as a crucial precursor in the synthesis of various high-value abietane-type diterpenes, exhibiting diverse pharmacological activities. Previous efforts to enhance miltiradiene production have primarily focused on the mevalonate acetate (MVA) pathway. However, limited emphasis has been placed on optimizing the supply of acetyl-CoA and NADPH. In this study, we constructed a platform yeast strain for miltiradiene production by reinforcing the biosynthetic pathway of geranylgeranyl diphosphate (GGPP) and acetyl-CoA, and addressing the imbalance between the supply and demand of the redox cofactor NADPH within the cytoplasm, resulting in an increase in miltiradiene yield to 1.31 g/L. Furthermore, we conducted modifications to the miltiradiene synthase fusion protein tSmKSL1-CfTPS1. Finally, the comprehensive engineering strategies and protein modification strategies culminated in 1.43 g/L miltiradiene in the engineered yeast under shake flask culture conditions. Overall, our work established efficient yeast cell factories for miltiradiene production, providing a foothold for heterologous biosynthesis of abietane-type diterpenes.

Bioinformatics Analysis of WRKY Family Genes in Erianthus fulvus Ness.

One of the most prominent transcription factors in higher plants, the WRKY gene family, is crucial for secondary metabolism, phytohormone signaling, plant defense responses, and plant responses to abiotic stresses. It can control the expression of a wide range of target genes by coordinating with other DNA-binding or non-DNA-binding interacting proteins. In this study, we performed a genome-wide analysis of the EfWRKY genes and initially identified 89 members of the EfWRKY transcription factor family. Using some members of the OsWRKY transcription factor family, an evolutionary tree was built using the neighbor-joining (NJ) method to classify the 89 members of the EfWRKY transcription factor family into three major taxa and one unclassified group. Molecular weights ranged from 22,614.82 to 303,622.06 Da; hydrophilicity ranged from (-0.983)-(0.159); instability coefficients ranged from 40.97-81.30; lipid coefficients ranged from 38.54-91.89; amino acid numbers ranged from 213-2738 bp; isoelectric points ranged from 4.85-10.06. A signal peptide was present in EfWRKY41 but not in the other proteins, and EfWRK85 was subcellularly localized to the cell membrane. Chromosome localization revealed that the WRKY gene was present on each chromosome, proving that the conserved pattern WRKYGQK is the family's central conserved motif. Conserved motif analysis showed that practically all members have this motif. Analysis of the cis-acting elements indicated that, in addition to the fundamental TATA-box, CAAT-box, and light-responsive features (GT1-box), there are response elements implicated in numerous hormones, growth regulation, secondary metabolism, and abiotic stressors. These results inform further studies on the function of EfWRKY genes and will lead to the improvement of sugarcane.

Black phosphorus assisted polyionic micelles with efficient PTX loading for remotely controlled release and synergistic treatment of drug-resistant tumors.

Nanomedicines have been widely used in the effective delivery of chemotherapeutic drugs due to their advantages such as increasing the half-life of drugs, selectively targeting tumor tissues, and thus reducing systemic toxicity. However, the low drug entrapment rate and the difficulty of real-controlled release at tumor sites hinder their further clinical translations. Here we have developed biodegradable polyionic micelles (PD-M) to facilitate black phosphorus (BP) encapsulation (PD-M@BP) for improved drug loading. With the introduction of BP, PTX-loaded PD-M@BP (PD-M@BP/PTX) with sizes of 124-162 nm exhibited superior encapsulation efficiency over 94% and excellent colloidal stability. Meanwhile, PD-M well protected BP from fast degradation to show the good photothermal performance under near-infrared (NIR) irradiation, thus achieving the remotely controlled fast PTX release due to micelle core melting and dissociation, accompanied by the synergistic photothermal tumor therapy. The in vivo results demonstrated that the PD-M@BP/PTX nanosystem not only realized significant inhibition of multi-drug resistant (MDR) cervical tumors (HeLa/PTXR tumor) by remote NIR-regulation, but also reduced the potential damage of chemotherapeutic drugs to the whole body, rendering these hybrid nanosystems as great tools to treat MDR tumors synergistically.

Turning Waste into Wealth: Remotely NIR Light-Controlled Precious Metal Recovery by Covalently Functionalized Black Phosphorus.

It is a great challenge to refine precious metals from e-wastes under mild conditions without hazardous reagents. Herein, black phosphorus (BP) was covalently functionalized with poly(N-isopropylacrylamide) (PNIPAM) to obtain thermo/near-infrared (NIR)-responsive BP-P for precious metal recovery. Precious metals (Au, Ag, and Pd) with higher redox potentials than BP-P could be efficiently recovered by reduction-driven enrichment. Taking Au as an example, the recovery process presented fast kinetics (<15 min), excellent selectivity, and high efficiency (≈98 %). Remote operation with NIR light could generate heat by BP, which induced the hydrophilic-to-hydrophobic transition of PNIPAM, allowing the spontaneous gathering, facile collection, and practical recycle of BP-P following Au extraction. Thanks to the unique features of BP-P, not only could high-quality Au nanoparticles (20-30 nm) be economically extracted (cost: $0.731-1.222 g-1 Au nanoparticles; 5-6 orders of magnitude lower than the market price), but also the formed BP-P-Au nanocomposites have potential application in hydrogen evolution reaction.

A flexible and salt-rejecting electrospun film-based solar evaporator for economic, stable and efficient solar desalination and wastewater treatment.

Recently, interfacial solar evaporation has been developed for water treatment. However, the high cost and low stability of solar evaporators significantly hinder their practical applications. In this study, layered graphene and polymethylmethacrylate were used to fabricate a composited film (GF) by electrospinning, which acted as a solar absorber. Together with a water transporter (polyurethane sponge) and a thermal insulator (polystyrene foam), the GF-based evaporator was constructed for solar distillation. Taking advantage of the porous three-dimensional structure of GF, the light path could be extended, rendering an efficient broadband solar absorption (92%). More importantly, although the content of layered graphene in the GF-based evaporator (1.75 g m-2) was only 5.8-17.5% of that in the current reported graphene-based evaporators (10-30 g m-2), a comparable water evaporation efficiency was acquired, which was induced by the much higher utilization efficiency of photothermal nanomaterials in the GF-based evaporator than that in the reported devices, ensuring its economic feasibility. Meanwhile, more than 99.9% heavy metal ions and 99.8% organic dye could be removed by the GF-based evaporator. Combining the merits of long-term and stable evaporation, salt rejection, and resistance to harsh environment, the GF-based evaporator was promising for freshwater recycling from both seawater and wastewater.