Polymer-Protein Nanovaccine Synthesized via Reactive Self-Assembly with Potential Application in Cancer Immunotherapy: Physicochemical and Biological Characterization In Vitro and In Vivo.

Nanovaccines composed of polymeric nanocarriers and protein-based antigens have attracted much attention in recent years because of their enormous potential in the prevention and treatment of diseases such as viral infections and cancer. While surface-conjugated protein antigens are known to be more immunoactive than encapsulated antigens, current surface conjugation methods often result in low and insufficient protein loading. Herein, reactive self-assembly is used to prepare nanovaccine from poly(ε-caprolactone) (PCL) and ovalbumin (OVA)-a model antigen. A rapid thiol-disulfide exchange reaction between PCL with pendant pyridyl disulfide groups and thiolated OVA results in the formation of nanoparticles with narrow size distribution. High OVA loading (≈70-80 wt%) is achieved, and the native secondary structure of OVA is preserved. Compared to free OVA, the nanovaccine is much superior in enhancing antigen uptake by bone marrow-derived dendritic cells (BMDCs), promoting BMDC maturation and antigen presentation via the MHC I pathway, persisting at the injection site and draining lymph nodes, activating both Th1 and Th2 T cell immunity, and ultimately, resisting tumor challenge in mice. This is the first demonstration of reactive self-assembly for the construction of a polymer-protein nanovaccine with clear potential in advancing cancer immunotherapy.

Efficacy and Related Factors of Artificial Femoral Head Replacement for Femoral Intertrochanteric Fracture and Nonunion: A Systematic Review and Meta-Analysis.

Background: An intertrochanteric fracture can cause ischemic necrosis in the femoral head, leading to negative effects. There are many types of implants for this fracture procedure, including metal-on-metal, metal-on-polyethylene, ceramic-on-ceramic, and ceramic-on-polyethylene, that are currently in use. The current modification is a hybrid prosthetic implant with high functional capacity compared with predecessors. This study aims to determine the procedure's efficacy in recovery, function restoration, complications, and cost-effectiveness. Methods: Our study used a total of 200 patients undergoing total hip arthroplasty and 135 patients undergoing semi-hip arthroplasty to determine the effectiveness of total hip arthroplasty and femoral head arthroplasty From May 2022 to May 2023. Using the RAOSOFT sampling technique, 132 and 101 in the observation and control group, respectively, the sample is obtained with a confidence interval of 95%, an error margin of 1%, and response interval confidence of 50%. This is a descriptive type of research that relies on a meta-analysis of the available data from PubMed, scholarly articles, and the Chinese biomedical database to gather the fundamental data needed to conduct the research. Data obtained is analyzed using SSPS and STATA and presented in tables showing a summary of the objective measured value. Result: In this study, the Harris joint score of patients in the total hip arthroplasty group was significantly higher than that of the control group, indicating that total hip arthroplasty can restore femoral head function, but still lacks absolute strength like half hip arthroplasty. Conclusions: Femoral head replacement is a complex procedure, but the efficacy in restoring the function is better. In conclusion, despite slow healing and regeneration, the efficacy of complete artificial femoral head replacement is higher in restoring function for various fractures.

Helper-Polymer Based Five-Element Nanoparticles (FNPs) for Lung-Specific mRNA Delivery with Long-Term Stability after Lyophilization.

Lipid nanoparticles (LNPs) carrying therapeutic mRNAs hold great promise in treating lung-associated diseases like viral infections, tumors, and genetic disorders. However, because of their thermodynamically unstable nature, traditional LNPs carrying mRNAs need to be stored at low temperatures, which hinders their prevalence. Herein, an efficient lung-specific mRNA delivery platform named five-element nanoparticles (FNPs) is developed in which helper-polymer poly(ß-amino esters) (PBAEs) and DOTAP are used in combination. The new strategy endows FNPs with high stability by increasing the charge repulsion between nanoparticles and the binding force of the aliphatic chains within the nanoparticles. The structure-activity relationship (SAR) shows that PBAEs with E1 end-caps, higher degrees of polymerization, and longer alkyl side chains exhibit higher hit rates. Lyophilized FNP formulations can be stably stored at 4 °C for at least 6 months. Overall, a novel delivery platform with high efficiency, specificity, and stability was developed for advancing mRNA-based therapies for lung-associated diseases.

Precise Synthesis of Concentric Ring, Helicoid, and Ladder Metallo-Polymers with Chevron-Shaped Monomers.

Molecular geometry represents one of the most important structural features and governs physical properties and functions of materials. Nature creates a wide array of substances with distinct geometries but similar chemical composition with superior efficiency and precision. However, it remains a formidable challenge to construct abiological macromolecules with various geometries based on identical repeating units, owing to the lack of corresponding synthetic approaches for precisely manipulating the connectivity between monomers and feasible techniques for characterizing macromolecules at the single-molecule level. Herein, we design and synthesize a series of tetratopic monomers with chevron stripe shape which serve as the key precursors to produce four distinct types of metallo-macromolecules with well-defined geometries, viz., the concentric hexagon, helicoid polymer, ladder polymer, and cross-linked polymer, via platinum-acetylide couplings. Concentric hexagon, helicoid, and ladder metallo-polymers are directly visualized by transmission electron microscopy, atomic force microscopy, and ultra-high-vacuum low-temperature scanning tunneling microscopy at the single-molecule level. Finally, single-walled carbon nanotubes (SWCNTs) are selected as the guest to investigate the structure-property relationship based on such macromolecules, among which the helicoid metallo-polymer shows high efficiency in wrapping SWCNTs with geometry-dependent selectivity.

Design of a UCST Polymer with Strong Hydrogen Bonds and Reactive Moieties for Facile Polymer-Protein Hybridization.

Polymer-protein hybrids have been extensively used in biomedical fields. Polymers with upper critical solution temperature (UCST) behaviors can form a hydrated coacervate phase below the cloud point (Tcp), providing themselves the opportunity to directly capture hydrophilic proteins and form hybrids in aqueous solutions. However, it is always a challenge to obtain a UCST polymer that could aggregate at a high temperature at a relatively low concentration and also efficiently bind with proteins. In this work, a UCST polymer reactive with proteins was designed, and its temperature responsiveness and protein-capture ability were investigated in detail. The polymer was synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization of acrylamide (AAm) and N-acryloxysuccinimide (NAS). Interestingly, taking advantage of the partial hydrolysis of NAS into acrylic acid (AAc), the obtained P(AAm-co-NAS-co-AAc) polymer exhibited an excellent UCST behavior and possessed good protein-capture ability. It showed a relatively higher Tcp (81 °C) at a lower concentration (0.1 wt %) and quickly formed polymer-protein hybrids with high protein loading and without losing protein bioactivity, and both the polymer and polymer-protein nanoparticles showed good cytocompatibility. All the findings are attributed to the unique structure of the polymer, which provided not only the strong and stable hydrogen bonds but also the quick and mild reactivity. The work offers an easy and mild strategy for polymer-protein hybridization directly in aqueous solutions, which may find applications in biomedical fields.

Detection of Proximal Caries Lesions on Bitewing Radiographs Using Deep Learning Method.

This study aimed to evaluate the validity of a deep learning-based convolutional neural network (CNN) for detecting proximal caries lesions on bitewing radiographs. A total of 978 bitewing radiographs, 10,899 proximal surfaces, were evaluated by two endodontists and a radiologist, of which 2,719 surfaces were diagnosed and annotated with proximal caries and 8,180 surfaces were sound. The data were randomly divided into two datasets, with 818 bitewings in the training and validation dataset and 160 bitewings in the test dataset. Each annotation in the test set was then classified into 5 stages according to the extent of the lesion (E1, E2, D1, D2, D3). Faster R-CNN, a deep learning-based object detection method, was trained to detect proximal caries in the training and validation dataset and then was assessed on the test dataset. The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic curve were calculated. The performance of the network in the overall and different stages of lesions was compared with that of postgraduate students on the test dataset. A total of 388 carious lesions and 1,435 sound surfaces were correctly identified by the neural network; hence, the accuracy was 0.87. Furthermore, 27.6% of lesions went undetected, and 7% of sound surfaces were misdiagnosed by the neural network. The sensitivity, specificity, PPV, and NPV of the neural network were 0.72, 0.93, 0.77, and 0.91, respectively. In contrast with the network, 52.8% of lesions went undetected by the students, yielding a sensitivity of only 0.47. The F1-score of the students was 0.57, while the F1-score of the network was 0.74 despite the accuracy of 0.82. A significant difference in the sensitivity was found between the model and the postgraduate students when detecting different stages of lesions (p < 0.05). For early lesions which limited in enamel and the outer third of dentin, the neural network had sensitivities all above or at 0.65, while students showed sensitivities below 0.40. From our results, we conclude that the CNN may be an assistant in detecting proximal caries on bitewings.

Research advance in lipid nanoparticle-mRNA delivery system and its application in CAR-T cell therapy.

Chimeric antigen receptor (CAR) T cell therapy has shown significant efficacy for hematological malignancies, however, it needs to be further optimized. Recently, the lipid nanoparticle (LNP)-mRNA delivery system as a nonviral gene transfer vector has gained rapid progress in CAR-T cell therapy. The claudin-6 (CLDN6) mRNA is delivered to antigen presenting cells (APCs) through LNP system, thereby enhancing the function of CLDN6 CAR-T cells for the clearance of solid tumor cells. For treatment of acute cardiac injury, the fibroblast activation protein (FAP) CAR mRNA can be delivered to T cells through LNP system for the in vivo production of FAP CAR-T cells, thereby blocking the process of myocardial fibrosis. The LNP-mRNA delivery system has advantages including having no integration in host genome, inexpensiveness, low toxicity and modifiability; on the other hand, it has certain disadvantages such as limited cell persistence caused by transient protein expression and limitations in preparation techniques. This article reviews the research advance in LNP-mRNA in vivo delivery system and its application in CAR-T cell therapy.

Self-assembled nanoparticles containing photosensitizer and polycationic brush for synergistic photothermal and photodynamic therapy against periodontitis.

BACKGROUND: Periodontitis is a chronic inflammatory disease in oral cavity owing to bacterial infection. Photothermal therapy (PTT) and photodynamic therapy (PDT) have many advantages for antibacterial treatment. As an excellent photosensitizer, indocyanine green (ICG) shows prominent photothermal and photodynamic performances. However, it is difficult to pass through the negatively charged bacterial cell membrane, thus limiting its antibacterial application for periodontitis treatment. RESULTS: In this work, self-assembled nanoparticles containing ICG and polycationic brush were prepared for synergistic PTT and PDT against periodontitis. First, a star-shaped polycationic brush poly(2-(dimethylamino)ethyl methacrylate) (sPDMA) was synthesized via atom transfer radical polymerization (ATRP) of DMA monomer from bromo-substituted ß-cyclodextrin initiator (CD-Br). Next, ICG was assembled with sPDMA to prepare ICG-loaded sPDMA (sPDMA@ICG) nanoparticles (NPs) and the physicochemical properties of these NPs were characterized systematically. In vitro antibacterial effects of sPDMA@ICG NPs were investigated in porphyromonas gingivalis (Pg), one of the recognized periodontitis pathogens. A ligature-induced periodontitis model was established in Sprague-Dawley rats for in vivo evaluation of anti-periodontitis effects of sPDMA@ICG NPs. Benefiting from the unique brush-shaped architecture of sPDMA polycation, sPDMA@ICG NPs significantly promoted the adsorption and penetration of ICG into the bacterial cells and showed excellent PTT and PDT performances. Both in vitro and in vivo, sPDMA@ICG NPs exerted antibacterial and anti-periodontitis actions via synergistic PTT and PDT. CONCLUSIONS: A self-assembled nanosystem containing ICG and polycationic brush has shown promising clinical application for synergistic PTT and PDT against periodontitis.

Poly-ß-hydroxybutyrate (PHB) in bioflocs alters intestinal microbial community structure, immune-related gene expression and early Cyprinid herpesvirus 2 replication in gibel carp (Carassius auratus gibelio).

The aquaculture system based on biofloc technology (BFT) showed positive effects on prevention of Cyprinid herpesvirus 2 (CyHV-2) infection in gibel carp (Carassius auratus gibelio), which is detrimental to health and causes seriously economic losses to aquaculture. However, the enhancement mechanism of BFT regarding immunity and disease resistance of cultured species is scarce. Poly-ß-hydroxybutyrate (PHB) has been proved as one of bioactive compounds in bioflocs. In this study, two groups (4% PHB supplementation diets and control with basal diets) with 30-day feeding were set to study the effect of PHB supplementation on immune-related gene expression by qRT-PCR, time-course CyHV-2 replication in vivo by qPCR and intestinal microbiota by illumine high-throughput sequencing. PHB supplementation significantly up-regulated transcriptional levels of eight immune-related genes, decreased cumulative mortality of gibel carp and early CyHV-2 replication in spleen in vivo (P < 0.05). Additionally, PHB changed the microbial structure but not diversity, and significantly increased beneficial bacteria such as Bacillus sp. KEGG pathway analysis by PICRUSt demonstrated that oral administration of PHB up-regulated abundances of genes responsible for seven pathways and down-regulated genes in eleven pathways. Histological structures of foregut, mindgut and hindgut were also affected. Our findings suggested that profitable effects of PHB on immunity and disease resistance might be gut microbiota-related, and regulated through pathways of enzymes secretion, replication and repair, and host immune system. This study will provide new insights into understanding the enhancing mechanism of BFT on immunity and disease resistance of cultured animals, and developing prebiotics/probiotics-based immunotherapies to improve animal health and disease resistance.

ß-hydroxybutyrate (ß-HB) exerts anti-inflammatory and antioxidant effects in lipopolysaccharide (LPS)-stimulated macrophages in Liza haematocheila.

Poly-ß-hydroxybutyrate (PHB) can be hydrolyzed to ß-hydroxybutyrate (ß-HB) in the intestinal tract of animals, and dietary PHB supplementation could enhance the immunity and disease resistance of aquatic animals. Antioxidant system is responsive to PHB stimuli via MAPK/PI3K-Akt/TNF/NF-κB/TCR/TLR signaling pathways. However, the precise immunopotentiation mechanism needs further study. In this study, macrophages from spleen in Liza haematocheila was used to study the effect of ß-HB on cell viability and antioxidant function to illustrate the immunopotentiation mechanism of PHB. The results showed that ß-HB (100 µg/mL) promoted the viability of macrophages and balanced the production of reactive oxygen species, but inhibited the excessive production of intracellular nitric oxide. In order to further explore the immunopotentiation mechanism of ß-HB, LPS (100 µg/mL) was used to induce the inflammation and investigated the inhibitory effect of ß-HB on inflammation. The results showed that LPS could induce inflammation successfully, and ß-HB exerted anti-inflammatory and antioxidant effects in LPS-stimulated macrophages. Compared with LPS stimuli alone, the expression of anti-inflammatory genes NF-κBIA, MAP3K8 and TLR5 in ß-HB pretreatment group was up-regulated, and the expression of pro-inflammatory genes TNFSF6, TNF-α, PI3K, NF-κB and TLR1 down-regulated. It suggested that ß-HB inhibited the inflammatory response by up-regulation of anti-inflammatory genes such as NF-κBIA, thereby enhancing the immunity of the body.

Engineering a Nanocomposite Interlayer for a Novel Ceramic-Based Forward Osmosis Membrane with Enhanced Performance.

Rational design of a high-performance defect-free polyamide (PA) layer on a robust ceramic substrate is challenging for forward osmosis (FO) water treatment applications. In this study, we first demonstrated a robust ceramic-based thin-film composite (TFC) FO membrane by engineering a novel nanocomposite interlayer of titanium dioxide and carbon nanotube (TiO2/CNT). The structural morphologies and properties were systematically characterized for different substrates (without interlayer, with TiO2 interlayer, or with TiO2/CNT interlayer) and the corresponding ceramic-based TFC-FO membranes. Introduction of low roughness nanocomposite interlayers with decreased pore size created an interface with improved surface characteristics, favoring the formation of a defect-free nanovoid-containing PA layer with high cross-linking degree. The resulting ceramic-based FO membrane had a water permeability of approximately 2 L/(m2 h bar) and a NaCl rejection of 98%, showing simultaneous enhancements in both compared to the control membrane without an interlayer. Mechanism analysis indicates that such a special nanocomposite interlayer not only provided more active sites for the formation of a thinner defect-free nanovoid-containing PA layer without penetration into substrate but also acted as a highly porous three-dimensional network structure for rapid water transport. This work provides a novel protocol for rational design and fabrication of a high-performance multilayered inorganic FO membrane as well as extended applications in water treatment with enhanced performance.

Emissive Metallacycle-Crosslinked Supramolecular Networks with Tunable Crosslinking Densities for Bacterial Imaging and Killing.

The chemical structures and topologies of the crosslinks in supramolecular networks play a crucial role in their properties and functions. Herein, the preparation of a type of poly(N-isopropylacrylamide) (PNIPAAM)-based supramolecular networks crosslinked by emissive hexagonal metallacycles is presented. The topological connections in these networks greatly affect their properties, as evidenced by their differences in absorption, emission, lower critical solution temperature, and modulus along with the variation of crosslinking densities. The integration of PNIPAAM and metallacycles in the networks benefits them improved bioavailability, making them serve as reagents for bacterial imaging and killing. This study provides a strategy to prepare cavity-crosslinked polymer networks for antibacterial applications.

Development of Robust Yeast Strains for Lignocellulosic Biorefineries Based on Genome-Wide Studies.

Lignocellulosic biomass has been widely studied as the renewable feedstock for the production of biofuels and biochemicals. Budding yeast Saccharomyces cerevisiae is commonly used as a cell factory for bioconversion of lignocellulosic biomass. However, economic bioproduction using fermentable sugars released from lignocellulosic feedstocks is still challenging. Due to impaired cell viability and fermentation performance by various inhibitors that are present in the cellulosic hydrolysates, robust yeast strains resistant to various stress environments are highly desired. Here, we summarize recent progress on yeast strain development for the production of biofuels and biochemical using lignocellulosic biomass. Genome-wide studies which have contributed to the elucidation of mechanisms of yeast stress tolerance are reviewed. Key gene targets recently identified based on multiomics analysis such as transcriptomic, proteomic, and metabolomics studies are summarized. Physiological genomic studies based on zinc sulfate supplementation are highlighted, and novel zinc-responsive genes involved in yeast stress tolerance are focused. The dependence of host genetic background of yeast stress tolerance and roles of histones and their modifications are emphasized. The development of robust yeast strains based on multiomics analysis benefits economic bioconversion of lignocellulosic biomass.

Effects of dietary poly-ß-hydroxybutyrate supplementation on the growth, immune response and intestinal microbiota of soiny mullet (Liza haematocheila).

Soiny mullet (Liza haematocheila) is an important economic fish species in China, but stress and diseases have seriously restricted its culture. There are no effective methods including vaccines to prevent or control these diseases. Alternative methods should be employed, such as using novel immunostimulant poly-ß-hydroxybutyrate (PHB). The present study aimed to evaluate effects of dietary PHB supplementation on the growth, antioxidant enzymes activity, immune-related genes expression and intestinal microbiota in soiny mullet. The fish was fed for 30 or 60 days with six diets at different PHB supplementation of 0, 0.5, 1, 2, 4 and 8%, named as groups P0, P0.5, P1, P2, P4 and P8. The results showed that the weight gain and specific growth rate of fish in P2 and P0.5 groups were significantly higher than those in control P0 group at 30 and 60 days, respectively (P < 0.05). The antioxidant enzymes activity of catalase and superoxide dismutase in serum were significantly increased in P0.5/P1/P2 groups after 30 days. The transcriptional levels of penicillin-binding protein A and interleukin-8 analyzed by qRT-PCR were significantly upregulated in P2 and P4 groups compared to those in P0/P0.5/P1/P8 groups at 30 days. The transcriptional level of major histocompatibility complex class II in P2 group was significantly upregulated, and aldehyde oxidase downregulated compared to P0 group. Intestinal microbiota analysis by Illumina high-throughput sequencing showed that the microbiota diversity was not changed significantly, but the microbiota structure shifted significantly post PHB treatment. At the phyla level, Firmicutes and Proteobacteria were predominant in both P0 and P2 groups. At the genus level, the relative abundance of Bacillus spp. in P2 group increased significantly, and abundance of Achromobacter spp. decreased significantly. KEGG pathway analysis by PICRUSt showed that oral administration PHB significantly upregulated abundances of genes responsible for 10 pathways and downregulated genes involved in 17 pathways. In conclusion, soiny mullet fed with 2% PHB supplemental diets for 30 days showed better growth performance, higher antioxidant enzymes activity and immune-related genes expression. Their regulation of growth and immunity might be related with the intestinal microbiota change post PHB supplementation. It will provide very useful basic information to study the regulation mechanism of PHB in aquatic animals, and provide good green method to prevent disease in soiny mullet.

Antioxidant system of soiny mullet (Liza haematocheila) is responsive to dietary poly-ß-hydroxybutyrate (PHB) supplementation based on immune-related enzyme activity and de novo transcriptome analysis.

As a dietary supplement, poly-ß-hydroxybutyrate (PHB) has been reported to positively influence growth, boost the immune system and enhance disease resistance in fish and shellfish. However, the protective mechanism is little known. Thus, the present study was conducted to evaluate the effect of PHB supplementation on immune-related enzyme activity and transcriptome-based gene expression in soiny mullet (Liza haematocheila). Results showed that dietary PHB supplementation could increase antioxidant enzyme activity, including total antioxidant capacity, catalase and superoxide dismutase. A total of 7,082,094,175 and 7,650,341,357 raw reads with mean length of 757 bp were obtained from control and PHB (dietary PHB supplementation at 2%) groups, respectively. There were 46,106 differentially expressed genes (DEGs) between control and PHB groups, including 21,828 upregulated and 24,278 downregulated DEGs. All the DEGs were classified into three gene ontology categories, and 312 DEGs related with immune system process and 760 with the response to a stimulus. Additionally, all DEGs were allocated to 261 Kyoto Encyclopedia of Gene and Genome pathways, and major immune-related pathways were detected, including MAPK/PI3K-Akt/TNF/NF-κB/TCR/TLR signaling pathways. Moreover, the regulation of several observed immune-related genes was confirmed by qRT-PCR. Altogether, this study suggests that antioxidant system is more effective for dietary PHB supplementation and lays the foundation for further study on the precise immunostimulatory mechanism of PHB. Hopefully, it provides insights into exploring biomarker for assessment of immunostimulants in fish culture.

Fluorescent metallacycle-cored polymers via covalent linkage and their use as contrast agents for cell imaging.

The covalent linkage of supramolecular monomers provides a powerful strategy for constructing dynamic polymeric materials whose properties can be readily tuned either by the selection of monomers or the choice of functional linkers. In this strategy, the stabilities of the supramolecular monomers and the reactions used to link the monomers are crucial because such monomers are normally dynamic and can disassemble during the linking process, leading to mixture of products. Therefore, although noncovalent interactions have been widely introduced into metallacycle structures to prepare metallosupramolecular polymers, metallacycle-cored polymers linked by covalent bonds have been rarely reported. Herein, we used the mild, highly efficient amidation reaction between alkylamine and N-hydroxysuccinimide-activated carboxylic acid to link the pendent amino functional groups of a rhomboidal metallacycle 10 to give metallacycle-cored polymers P1 and P2, which further yielded nanoparticles at low concentration and transformed into network structures as the concentration increased. Moreover, these polymers exhibited enhanced emission and showed better quantum yields than metallacycle 10 in methanol and methanol/water (1/9, vol/vol) due to the aggregation-induced emission properties of a tetraphenylethene-based pyridyl donor, which serves as a precursor for metallacycle 10. The fluorescence properties of these polymers were further used in cell imaging, and they showed a significant enrichment in lung cells after i.v. injection. Considering the anticancer activity of rhomboidal Pt(II) metallacycles, this type of fluorescent metallacycle-cored polymers can have potential applications toward lung cancer treatment.

Fluorescent Metallacage-Core Supramolecular Polymer Gel Formed by Orthogonal Metal Coordination and Host-Guest Interactions.

Herein, we report the preparation of a multifunctional metallacage-core supramolecular gel by orthogonal metal coordination and host-guest interactions. A tetragonal prismatic cage with four appended 21-crown-7 (21C7) moieties in its pillar parts was first prepared via the metal-coordination-driven self-assembly of cis-Pt(PEt3)2(OTf)2, tetraphenylethene (TPE)-based sodium benzoate ligands and linear dipyridyl ligands. Further addition of a bisammonium linker to the cage delivered a supramolecular polymer network via the host-guest interactions between the 21C7 moieties and ammonium salts, which formed a supramolecular gel at relatively higher concentrations. Due to the incorporation of a TPE derivative as the fluorophore, the gel shows emission properties. Multiple stimuli responsiveness and good self-healing properties were also observed because of the dynamic metal coordination and host-guest interactions used to stabilize the whole network structure. Moreover, the storage and loss moduli of the gel are 10-fold those of the gel without the metallacage cores, indicating that the rigid metallacage plays a significant role in enhancing the stiffness of the gel. The studies described herein not only enrich the functionalization of fluorescent metallacages via elegant ligand design but also provide a way to prepare stimuli-responsive and self-healing supramolecular gels as robust and smart materials.

Construction of Metallacage-Cored Supramolecular Gel by Hierarchical Self-Assembly of Metal Coordination and Pillar[5]arene-Based Host-Guest Recognition.

In this work, a Pd2 L4 metallacage 2•([BF4 ]- )4 with four pillar[5]arene units is first prepared and characterized by 1D multinuclear NMR (1 H, 11 B, and 19 F NMR), 2D 1 H-1 H correlation spectra, 1 H-13 C heteronuclear single quantum coherence, and diffusion-ordered NMR spectroscopy, and electrospray ionization time-of-flight mass spectrometry. By the introduction of a ditopic guest molecule 3 into a chloroform solution of 2•([BF4 ]- )4 , a supramolecular polymer network gel is successfully constructed based on the metal coordination interactions and host-guest recognition between the pillar[5]arene units of 2•([BF4 ]- )4 and neutral ditopic guest molecule 3. The temperature and pH responsivenesses of the supramolecular gel are studied, which are further employed for the controlled release of different cargos. As a demonstration, emodin and methylene blue are trapped in the cavities of the metallacage and in the pores of the supramolecular gel, respectively. Methylene blue is first released along with the gel-sol transition while emodin is then released by the further addition of acid to destroy the metallacage. This study explores the use of metallacage-cored supramolecular network gels for sequential controlled release and contributes to the development of smart and adaptive materials.

Antitumor Activity of a Unique Polymer That Incorporates a Fluorescent Self-Assembled Metallacycle.

Despite the well-known anticancer activity of mono- and multinuclear platinum complexes, studies of the antitumor performances of platinum-based supramolecular coordination complexes are rare. Herein, we report on the synthesis of a four-armed amphiphilic copolymer, Pt-PAZMB-b-POEGMA, containing a metallacycle M, in which the tetraphenylethene derivative acts as an aggregation-induced emissive fluorescent probe for live cell imaging and the 3,6-bis[trans-Pt(PEt3)2]phenanthrene (PhenPt) is an anticancer drug. This copolymer was further self-assembled into nanoparticles of different sizes and vesicles depending upon the experimental conditions. The impacts of the morphology and size of the assemblies on their endocytic pathways, uptake rates, internalization amounts, and cytotoxicities were investigated. The self-assemblies were further employed to encapsulate doxorubicin (DOX) to achieve a synergistic anticancer effect. Controlled drug release was also realized via amphiphilicity changes and was driven by a glutathione-induced cascade elimination reaction. The DOX-loaded nanoparticles of around 50 nm in size exhibited an excellent antitumor performance as well as a low systemic toxicity, due to an enhanced permeability and retention effect.

Selective extraction and determination of chlorogenic acids as combined quality markers in herbal medicines using molecularly imprinted polymers based on a mimic template.

We describe a solid-phase extraction adsorbent based on molecularly imprinted polymers (MIPs), prepared with use of a mimic template. The MIPs were used for the selective extraction and determination of three chlorogenic acids as combined quality markers for Lonicera japonica and Lianhua qingwen granules. The morphologies and surface groups of the MIPs were assessed by scanning electron microscopy, Brunauer-Emmett-Teller surface area analysis, and Fourier transform infrared spectroscopy. The adsorption isotherms, kinetics, and selectivity of the MIPs were systematically compared with those of non-molecularly imprinted polymers. The MIPs showed high selectivity toward three structurally similar chlorogenic acids (chlorogenic acid, cryptochlorogenic acid, and neochlorogenic acid). A procedure using molecularly imprinted solid-phase extraction coupled with high-performance liquid chromatography was established for the determination of three chlorogenic acids from Lonicera japonica and Lianhua qingwen granules. The recoveries of the chlorogenic acids ranged from 93.1% to 101.4%. The limits of detection and limits of quantification for the three chlorogenic acids were 0.003 mg g-1 and 0.01 mg g-1, respectively. The newly developed method is thus a promising technique for the enrichment and determination of chlorogenic acids from herbal medicines. Graphical Abstract Mimic molecularly imprinted polymers for the selective extraction of chlorogenic acids.