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Pathogenic fungal infection is a major clinical threat because pathogenic fungi have developed resistant mechanisms to evade the innate immune response, especially interactions with macrophages. Herein, a strategy to activate immune responses of macrophages to fungi based on near-infrared (NIR) responsive conjugated polymer nanoparticles (CPNs-M) is reported for antifungal immunotherapy. Under NIR light irradiation, CPNs-M exposes β-glucan on the surface of fungal conidia by photothermal damage and drug released from CPNs-M. The exposed β-glucan elicits macrophage recognition and subsequently activates calcium-calmodulin (Ca

The gated state of anion channels is involved in the regulation of proliferation and migration of tumors. Specific regulators are urgently needed for efficacious cancer ablation. For this purpose, it is essential to understand the molecular mechanisms of interaction between the regulators and anion channels and apply this knowledge to regulate anion channels. Transmembrane 16A (TMEM16A) is the molecular basis of the calcium-activated chloride channels. It is an anion channel activated by Ca

The regulation of reactive oxygen species (ROS)-sensitive calcium (Ca

Mild-temperature photothermal therapy (PTT) is being extensively explored because it causes less injury to normal cells. However, the effect of mild-temperature PTT is decreased because of heat shock protein (HSP) overexpression. To solve this problem, we designed functional conjugated polymer nanoparticles (CPNs-G) that enhance the mild-temperature photothermal effect. Upon near-infrared (NIR) light irradiation, CPNs-G generate local heat to realize the photothermal effect. Meanwhile, the increased temperature enhances the catalytic activity of GOx, thus impeding the generation of adenosine triphosphate (ATP) and inhibiting HSP expression. Therefore, this work provides a strategy for overcoming thermoresistance through an enzyme-mediated starvation effect regulated by NIR light.

Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bidirectional mechanical exchange is crucial for many cell functions, it remains poorly understood. Key challenges are that the majority of available matrices for such studies, either natural or synthetic, are difficult to control or lack biological relevance. Here, we use a synthetic, yet highly biomimetic hydrogel based on polyisocyanide (PIC) polymers to investigate the effects of the fibrous architecture and the nonlinear mechanics on cell-matrix interactions. Live-cell rheology was combined with advanced microscopy-based approaches to understand the mechanisms behind cell-induced matrix stiffening and plastic remodeling. We demonstrate how cell-mediated fiber remodeling and the propagation of fiber displacements are modulated by adjusting the biological and mechanical properties of this material. Moreover, we validate the biological relevance of our results by demonstrating that cellular tractions in PIC gels develop analogously to those in the natural ECM. This study highlights the potential of PIC gels to disentangle complex bidirectional cell-matrix interactions and to improve the design of materials for mechanobiology studies. ispartof: Proc Natl Acad Sci U S A vol:120 issue:15 pages:e2216934120- ispartof: location:United States status: published

Fabricating antibacterial hydrogels with antimicrobial drugs and synthetic biocompatible biomimetic hydrogels is a promising strategy for practical medical applications. Here, we report a bicomponent hydrogel composed of a biomimetic polyisocyanopetide (PIC) hydrogel and a photodynamic antibacterial membrane-intercalating conjugated oligoelectrolyte (COE). The aggregation behavior and aggregate size of the COEs in water can be regulated using the PIC hydrogel, which could induce COEs with higher reactive oxygen species (ROS) production efficiency and increased association of COEs toward bacteria, therefore enhancing the antibacterial efficiency. This strategy provides a facile method for developing biomimetic hydrogels with high antibacterial capability.

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activating therapy has received wide attention due to its capacity to precisely induce cancer cell apoptosis. However, drug resistance and the poor pharmacokinetic properties of TRAIL protein are obstacles in TRAIL-based therapy for cancer. Herein, a strategy is developed to remotely control and specifically initiate TRAIL-mediated apoptotic signaling to promote TRAIL-resistant cancer cell apoptosis using near-infrared (NIR) light-absorbing conjugated polymer nanoparticles (CPNs). Upon 808 nm laser excitation, the promoter 70 kilodalton heat shock protein (HSP70) initiates transcription of the TRAIL gene in response to heat shock, thereby expressing TRAIL protein in breast cancer cells, which activates the TRAIL-mediated apoptosis signaling pathway. Simultaneously, the CPNs locally release W-7, which targets calmodulin (CaM) and further promotes caspase-8 cleavage and enhances cancer cell apoptosis. Both

Glyco‐assemblies derived from amphiphilic sugar‐decorated block copolymers (ASBCs) have emerged prominently due to their wide application, for example, in biomedicine and as drug carriers. However, to efficiently construct these glyco‐assemblies is still a challenge. Herein, we report an efficient technology for the synthesis of glyco‐inside nano‐assemblies by utilizing RAFT polymerization of a galactose‐decorated methacrylate for polymerization‐induced self‐assembly (PISA). Using this approach, a series of highly ordered glyco‐inside nano‐assemblies containing intermediate morphologies were fabricated by adjusting the length of the hydrophobic glycoblock and the polymerization solids content. A specific morphology of complex vesicles was captured during the PISA process and the formation mechanism is explained by the morphology of its precursor and intermediate. Thus, this method establishes a powerful route to fabricate glyco‐assemblies with tunable morphologies and variable sizes, which is significant to enable the large‐scale fabrication and wide application of glyco‐assemblies., Glyco‐inside nano‐assemblies containing numerous intermediate morphologies are fabricated by leveraging RAFT polymerization of a galactose‐decorated monomer for polymerization‐induced self‐assembly. This method establishes a powerful route to fabricate glyco‐inside nano‐assemblies with tunable morphologies and variable sizes, which is significant to expand the large‐scale fabrication and wide application of glyco‐assemblies.

Utilizing solar energy for hydrogen production by combining light-activated materials and biocatalysts has become a promising alternative to fossil fuels. Herein, a feasible and simple bio-hybrid complex based on water-soluble oligofluorene (OF), polythiophene (PTP) and Rhodopseudomonas palustris (R. palustris), one kind of photosynthetic bacteria, was constructed for enhancing photocatalytic hydrogen production. Under the irradiation of visible light, there was fluorescence resonance energy transfer (FRET) between OF and PTP, which amplified photoelectron signals and transferred electrons via PTP to methyl viologen (MV2+), an electron mediator that established electron transfer pathways between organic materials and R. palustris. Hydrogen production involving R. palustris was catalyzed by nitrogenase. It is noteworthy that MV2+ was reduced to MV+˙ and transferred electrons to nitrogenase in R. palustris, converting protons and electrons to molecular hydrogen. Besides, triethanolamine (TEOA) was added as an electron donor to provide electrons to PTP. The proposed OF/PTP/MV2+/TEOA/R. palustris system provided a feasible strategy for photocatalytic hydrogen production with low-cost and easily implemented techniques.

A new concept named “rotating magnetocaloric effect (RMCE)” has been proposed and attracted more attention recently. Unlike the traditional MCE that is achieved by moving the magnetic refrigerant in and out of magnetic field, RMCE can be realized by rotating the anisotropic material within the static field, thus implying the possible higher efficiency and simpler device. However, most studies on RMCE are concentrated on single crystals, which are generally more expensive and difficult to prepare in comparison with polycrystals. Therefore, it is highly desirable to search polycrystalline materials with high RMCE. Here, the textured HoNiSi polycrystal is reported to show a giant RMCE, e.g., the rotating magnetic entropy change (−ΔSR) are 18.5 and 26.7 J/kg K and rotating adiabatic temperature change (ΔTR) are 7.0 and 13.4 K under 2 and 5 T, respectively. This giant RMCE over a wide temperature range especially under low field suggests textured HoNiSi as promising material for practical application of rotary magnetic refrigeration. Moreover, the large magnetic anisotropy of HoNiSi is explained by the single-ion magnetic anisotropy theory, and the coherent orientation of crystallographic texture and rare-earth ion moments leads to the large RMCE in the textured HoNiSi polycrystal. This work reveals that the strongly coherent orientation of crystallographic texture and rare-earth ion moments is a key to realize large RMCE in polycrystalline materials.

Hybrid biomimetic hydrogels with enhanced reactive oxygen species (ROS)-generation efficiency under 600 nm light show high antibacterial activity. The hybrid gels are composed of helical tri(ethylene glycol)-functionalized polyisocyanides (PICs) and a conformation-sensitive conjugated polythiophene, poly(3-(3 '-N,N,N-triethylammonium-1 '-propyloxy)-4-methyl-2,5-thiophene chloride) (PMNT). The PIC polymer serves as a scaffold to trap and align the PMNT backbone into a highly ordered conformation, resulting in redshifted, new sharp bands in the absorption and fluorescence spectra. Similar to PIC, the hybrid closely mimics the mechanical properties of biological gels, such as collagen and fibrin, including the strain stiffening properties at low stresses. Moreover, the PMNT/PIC hybrids show much higher ROS production efficiency under red light than PMNT only, leading to an efficient photodynamic antimicrobial effect towards various pathogenic bacteria.

CO2-controlled assembly of conjugated polymer and boron nitride (BN) was fabricated via electrostatic and hydrophobic interactions between the BN fiber and conjugated polymer of PFBT containing fluorene units and 2,1,3-benzothiadiazole units. CO2, an effective and green stimulus for regulating the assembly of PFBT and BN fibers, leads to an obvious fluorescence variation. Moreover, PFBT enables the assembly with the signal amplification and light-harvesting properties. This work provides a new triggering method to construct intelligent conjugated polymer-based platform, and offers fluorescence monitoring strategy for carbon dioxide capture.

Both of carbon dioxide (CO2) and near-infrared (NIR) light as triggers for non-invasive remotely control are attracting wide attentions due to their good biocompatibility and easy operation. Here, CO2/NIR light dual controlled nanoparticles are proposed to remotely regulate the unzipping of dsDNA by using imidazole functionalized conjugated polymer nanoparticles (imidazole-CPNs). The dsDNA successfully coats on the shell of imidazole-CPNs to form imidazole-CPNs/dsDNA assembly due to intensively electrostatic interaction triggered by CO2. Furthermore, the unzipping process of dsDNA is remotely controlled by NIR light based on the photothermal effect, and it can be readily monitored by the fluorescence intensity of ethidium bromide (EB) and CD spectra of dsDNA. Thus, dual stimulation responsive imidazole-CPNs effectively control dsDNA unzipping under CO2 stimulus and NIR light, promising a new direction in the biological applications of DNA, such as the treatments of diseases caused by gene duplication abnormality.

Herein, we have developed a composite antibacterial hydrogel with photodynamic therapy (PDT) and photothermal therapy (PTT) antibacterial capabilities, triggered by white light and NIR light irradiation. A water-insoluble conjugated polymer (PDPP) with photothermal ability was prepared into nanoparticles by the nanoprecipitation method, and the cell-penetrating peptide TAT was grafted on the surface of the nanoparticles. Based on our previous work that developed a hybrid hydrogel with an enhanced PDT effect from polyisocyanide (PIC) hydrogel and cationic conjugated polythiophene (PMNT), PDPP nanoparticles (CPNs-TAT) with photothermal ability are introduced to realize the synergistic antibacterial effect of PDT and PTT. Using the PIC hydrogel to combine PIC and CPNs-TAT has the following advantages. First, the PIC hydrogel can regulate the aggregation state of PMNT, making it better dispersed and improving its capacity of reactive oxygen species (ROS) production. Second, CPNs-TAT can be uniformly dispersed in the PIC hybrid, thereby avoiding the toxicity caused by too high local concentration, achieving a uniform increase in system temperature, and enhancing the therapeutic effect of PTT. Third, the PIC hybrid has the synergistic treatment effect of PDT and PTT. The PIC hybrid intelligently regulates its antibacterial ability through white light and NIR light, which can be used in the white light and NIR light areas. When irradiated with white light and NIR light sequentially, synergistic PDT and PTT exhibit stronger antibacterial ability than PDT or PTT alone. The combination of two antibacterial methods realizes the dual-control antibacterial hydrogel of PDT and PTT and provides an antibacterial mode based on PIC hybrids. Therefore, the PIC hybrids are promising as an antibacterial excipient for clinical wounds.

By coating photosynthetic bacteria of Rhodopseudomonas palustris with conjugated polymers nanoparticles modified with positively charged peptide TAT (CPNs-TAT), a bio-optical hybrid composite of R....

Calmodulin (CaM), as a calcium binding protein involved in the signal pathways of many life activities such as cell proliferation and apoptosis, can be regulated with the near-infrared (NIR) light-based photothermal conversion. Here, we build a conjugated polymer nanoparticle (CPNs-C) by assembling polypyrrole dione and dipalmitoyl phosphatidylethanolamine-polyethylene glycol-maleimide with a calmodulin antibody modified on the surface, which is NIR light-responsive for photothermally inducing apoptosis of cancer cells. Under near-infrared light irradiation, protein kinase B (Akt) and phosphatidylinositol 3-kinase, which bind to CaM, reduce the degree of phosphorylation due to the photothermal effect of CPNs-C, thus inhibiting the recruitment of Akt on the cell membrane. Therefore, the phosphorylation of GSK-3β downstream of the signaling pathway is reduced, and the phosphorylation of FoxO3a is enhanced, which can promote apoptosis of cancer cells. Compared with the photothermal effect of traditional CPNs, CPNs-C exhibits higher efficiency to regulate signaling pathways to promote cancer cells toward apoptosis. This strategy of utilizing NIR light to regulate the tumor apoptotic signaling pathway provides an effective way to enhance cancer cell apoptosis with high efficiency.

Cancer cells survive by relying on oxidative stress defense against the accumulation of reactive oxygen species (ROS) during tumor formation. ROS-sensitive TRPA1 ion channels are overexpressed in breast cancer cells and induce a large influx of Ca

Hepatocellular carcinoma development is closely related to the changes in tissue mechanics induced by excess collagen deposition and crosslinking, which leads to liver fibrosis and malignant progression. The role of matrix stiffness has been widely assessed using various linearly elastic materials. However, the liver, like many soft tissues, also exhibits nonlinear elasticity by strain-stiffening, allowing cells to mechanically interact with their micromilieus which has attracted much attention in cellular processes recently. Here, we use a biomimetic hydrogel grafting of GRGDS peptide with tunable nonlinear mechanical properties, polyisocyanides (PIC), to investigate the influence of strain-stiffening on HepG2 liver cancer cell behavior by tuning PIC polymer length. Compared to short PIC polymer with lower critical stress, PIC hydrogels composed of long polymer with higher critical stress promote the motility and invasiveness of HepG2 cells, and induce more actin stress fibers and higher expression level of mechanotransducer YAP and its nuclear translocation. Strikingly, the expression of calcium-activated potassium channel KCa3.1, an important biomarker in hepatocellular carcinoma, is also affected by the mechanical property of PIC hydrogels. It was also shown that downregulating the KCa3.1 channel can be achieved by inhibiting the formation of actin fibers. Our findings imply that the strain-stiffening property of PIC hydrogels affects the expression of KCa3.1 potassium channel via mediating cytoskeletal stress fiber formation, and ultimately influences the liver carcinoma cell functional response. STATEMENT OF SIGNIFICANCE: The effect of nonlinear elasticity by strain-stiffening, is assessed in HepG2 liver cancer cell behavior by using a biomimetic hydrogel with tunable mechanical properties, polyisocyanides (PIC). PIC gels with higher critical stress promote the motility and invasiveness of HepG2 cells and induce upregulated expression levels of KCa3.1 potassium channel and YAP, but which can be suppressed by inhibiting the formation of actin fibers. Our findings imply that the strain-stiffening property of PIC gels influences the expression of KCa3.1 potassium channel via mediating cytoskeletal stress fiber formation and, ultimately affects the liver carcinoma cell functional response. ispartof: ACTA BIOMATERIALIA vol:148 pages:152-162 ispartof: location:England status: published

Graphene quantum dots (GQDs) have been successfully used as a highly sensitive probe for the sensing of formaldehyde (HCHO) in an aqueous solution. Through static quenching, the probe utilizes the interaction between HCHO and GQDs to trigger the “turn off” fluorescence response, and has good selectivity. The probe can detect HCHO in a pure aqueous solution, and it also can still detect HCHO in a complex environment with a pH range from 4 to 10. The concentration of HCHO and the fluorescence intensity of GQDs show a good linear relationship within the range of HCHO of 0–1 μg/mL, which was much more sensitive than previous reports. The limit of HCHO detection by GQDs is about 0.0515 μg/mL. In addition, we successfully applied it to the actual food inspection. It is proved to be a selective, sensitive and visualized method to check whether the concentration of HCHO in the foods exceeds the regulatory limit, which presents a potential application in food safety testing.

Cells are normally cultured in 2D environment, which is usually inconsistent with the real microenvironment in vivo, and it is rarely reported that an effective cancer cell killing process occurs in a 3D network environment. Herein, a kind of new biomimetic composite hydrogel which can achieve 3D cell culture has been prepared and constructed by assembly of polyisocyanopeptide (PIC) with cationic oligo (p-phenylene vinylene) (OPV). The polymer chains of PIC can be bound and frizzled to form a 3D network when the temperature rises above the gelation temperature, followed by encapsulating the cells into biomimetic composite hydrogel. Cells grow and proliferate well in 3D composite hydrogels with excellent cell viability. When the cells undergo cancerization or microbial infection during the 3D culture, the addition of the luminol luminescence system can cause a strong bioluminescence resonance energy transfer (BRET) process to produce highly active reactive oxygen species (ROS) in 3D culture and kill the ca...

The effects of Cu substitution for Ni atoms on the magnetic and magnetocaloric properties have been investigated in Mn0.8Fe0.2Ni1-xCuxGe (x = 0.05–0.3) compounds. The substitution of Cu leads to the larger separation of Mn atoms, which stabilizes the hexagonal phase and thus reduces the structural transition temperature Tstr. Moreover, the larger separation of nearest-neighbor Mn atoms weakens the ferromagnetic (FM) coupling in TiNiSi-type orthorhombic phase and results in the spiral antiferromagnetic (AFM) and more antiparallel AFM state with increasing Cu content. Similarly, the Ni2In-type hexagonal phase also changes from FM state to weak-magnetic spin-glass-like state with the introduction of Cu. The x = 0.05 compound shows a conventional magnetocaloric effect (MCE) due to the magnetostructural transformation from PM hexagonal phase to FM orthorhombic phase. On the contrary, the x = 0.1 compound undergoes the antiferromagnetically magnetostructural transition from FM hexagonal phase to AFM orthorhombic phase, which leads to a high inverse MCE. This large inverse MCE could be utilized in novel magnetic refrigerator to improve the refrigeration efficiency and applied for magnetic refrigeration of natural gas liquefaction.

Excess aggregation of amyloid β peptide (Aβ) is a fatal cause of Alzheimer's disease (AD), which leads to physiological toxicity. Inhibiting and disaggregating the Aβ aggregates is an effective strategy to reduce physiological toxicity in neuronal cells. Herein, conjugated polymer-based thermoresponsive micelles (CPMs) were designed with an efficient thermoresponsive surface and a reactive-oxygen-species (ROS)-generating core. In this work, the CPMs exhibited a strong capability to capture the toxic Aβ aggregates at physiological temperature. Under white-light irradiation, ROS was generated in the CPMs, and the toxic Aβ aggregates were efficiently disaggregated through the oxidation of ROS, leading to appropriate Aβ homeostasis between aggregation and disaggregation and reduced the Aβ-induced cytotoxicity. Therefore, the multifunctional micelles of CPMs with both capturing shells and ROS functional cores present a promising strategy to reduce Aβ fibrillation-induced cytotoxicity.

The magnetic and rotating magnetocaloric properties in textured Tb3NiGe2 compound were investigated. Two successive magnetic transitions, a ferrimagnetic to antiferromagnetic (AFM)-like transition at Tt = 130 K and an AFM to paramagnetic (PM)-like transition at TN = 144 K, are observed. Besides, a magnetic-field-induced antiferromagnetic-ferromagnetic metamagnetic transition occurs in the temperature range of Tt ∼ TN. Large rotating magnetic entropy changes, together with considerable adiabatic temperature changes and refrigeration capacity, are obtained in textured Tb3NiGe2 compound. Moreover, the equivalence of different calculation methods for rotating magnetocaloric effect (RMCE) is discussed mathematically. The large RMCE with excellent thermal and magnetic reversibility suggests textured Tb3NiGe2 compound as an attractive candidate for novel magnetic refrigerant.

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The synthetic control over pore structure and multifunctionality remain highly desirable for conjugated microporous polymers (CMPs). Here, we demonstrate that the 1,10-phenanthroline-like S,N-heter...

A drug carrier system of the hybrid nanoparticles based on the redox-responsive P[(2-((2-((camptothecin)-oxy)ethyl)disulfanyl)ethylmethacrylate)- co -(2-( d -galactose)methylmethacryl-ate)] (P(MACPTS- co -MAGP)) and AgNPs is developed to deliver the anti-cancer drug camptothecin (CPT) and monitor the drug release by the recovery of the fluorescence of CPT. CPT is linked to the polymer side-chains via a redox-responsive disulfide bond, attaching on the surface of AgNPs and leading to the quenching of CPT fluorescence (“off” state) due to the nanoparticle surface energy transfer (NSET) effect. Upon the exposure to glutathione (GSH), the disulfide bond is cleaved to release CPT, resulting in the recovery of the fluorescence of CPT (“on” state). The system offers a platform to track the CPT delivery and releasing in real time

Textured Ho2GdAl2 alloy exhibits highly anisotropic magnetic properties due to the coexistence of preferred crystallographic orientation and magnetocrystalline anisotropy (MCA). The variation in MCA energy (Ea) induced by the rotation of textured Ho2GdAl2 from a perpendicular to parallel direction under constant field results in a rotating magnetocaloric effect (MCE), which is larger than the conventional MCE. Moreover, the peaks of rotating magnetic entropy change (ΔSR) and rotating adiabatic temperature change (ΔTad,R) broaden asymmetrically towards low temperatures due to the different variation of MCA below and above the Curie temperature TC, thus leading to a table-like rotating MCE over the liquefaction temperature of natural gas.

Hybrid nanocomposites consisting of uniform Fe 3 O 4 nanoparticles and boron nitride (BN) nanospheres were synthesized via an ethanol-thermal reaction method. The spherical BN nanoparticles (BNNSs) with average diameter 150 nm have been uniformly coated with dense ultra-small Fe 3 O 4 nanoparticles (with average diameter of 10 nm), forming novel Fe 3 O 4 @BNNS nanocomposites. Magnetic measurement by using vibrating sample magnetometer (VSM) indicates that the Fe 3 O 4 coating is superparamagnetic, and the nanocomposites can be physically manipulated at a low magnetic field. Preliminary biocompatibility study has also been performed to evaluate the toxicity of the nanocomposites. The nanocomposites show cytocompatibility at low concentration and have little effect on cell viability of MCF-7, MCF-10 and Hela cell lines. The Fe 3 O 4 @BNNS nanocomposites may find a wide range of potential applications including water treatment, catalysts, carriers for boron neutron capture therapy and magnetic-targeted drug delivery.

A novel magnetic/fluorometric bimodal sensor was built from carbon dots (CDs) and MnO2. The resulting sensor was sensitive to glutathione (GSH), leading to apparent enhancement of magnetic resonance (MR) and fluorescence signals along with visual changes. The bimodal detection strategy is based on the decomposition of the CDs-MnO2 through a redox reaction between GSH and MnO2. This process causes the transformation from non-MR-active MnO2 to MR-active Mn(2+), and is accompanied by fluorescence restoration of CDs. Compared with a range of other CDs, the polyethylenimine (PEI) passivated CDs (denoted as pCDs) were suitable for detection due to their positive surface potential. Cross-validation between MR and fluorescence provided detailed information regarding the MnO2 reduction process, and revealed the three distinct stages of the redox process. Thus, the design of a CD-based sensor for the magnetic/fluorometric bimodal detection of GSH was emphasized for the first time. This platform showed a detection limit of 0.6 μM with a linear range of 1-200 μM in the fluorescence mode, while the MR mode exhibited a linear range of 5-200 μM and a GSH detection limit of 2.8 μM with a visible change being observed rapidly at 1 μM in the MR images. Furthermore, the introduction of the MR mode allowed the biothiols to be easily identified. The integration of CD fluorescence with an MR response was demonstrated to be promising for providing detailed information and discriminating power, and therefore extend the application of CDs in sensing and imaging.

To overcome the adverse effects of conventional chemotherapy for cancers, various nanoparticles based drug delivery systems have been developed. However, nanoparticles delivering drugs directly to kill tumor cells still faced with challenges, because tumors possessed adopt complex mechanism to resist damages, which compromised the therapeutic efficacy. TMEM16A/CaCCs (Calcium activates chloride channels) has been identified to be overexpressed in lung adenocarcinoma which can serve as a novel tumor specific drug target in our previous work. Here, we developed a novel dual-targeted antitumor strategy via designing a novel nano-assembled, pH-sensitive drug-delivery system loading with specific inhibitors of TMEM16A against lung adenocarcinoma. For validation, we assayed the novel dual-targeting therapy on xenograft mouse model which exhibited significant antitumor activity and not affect mouse body weight. The dual targeting therapy accomplished in this study will shed light on the development of advanced antitumor strategy.

Thermosensitive polymers show an entropy-driven transition from a well-solvated to a poorly solvated polymer chain, resulting in a more compact globular conformation. The transition at the lower critical solution temperature (LCST) is often sharp, which allows for a wide range of smart material applications. At the LCST, oligo(ethylene glycol)-substituted polyisocyanides (PICs) form soft hydrogels, composed of polymer bundles similar to biological gels, such as actin, fibrin and intermediate filaments. Here, we show that the LCST of PICs strongly depends linearly on the length of the ethylene glycol (EG) tails; every EG group increases the LCST and thus the gelation temperature by nearly 30 °C. Using a copolymerisation approach, we demonstrate that we can precisely tailor the gelation temperature between 10 °C and 60 °C and, consequently, tune the mechanical properties of the PIC gels.

An electrostatic complex combining anionic water-soluble conjugated polythiophene (PTP) with commercial cationic porphyrin ([5,10,15,20-tetrakis(4-(trimethylammonio)-phenyl)-21H,23H-porphine tetratosylate] (TMP)) has been designed for rapid and simple detection of bacteria infection in drinking water by applying fluorescence resonance energy transfer (FRET) strategy. There is efficient FRET from PTP to TMP for the electrostatic complex of PTP/TMP. Upon the addition of bacteria, the cationic TMP is adsorbed tightly to the negatively charged membrane surface of bacteria through electrostatic interactions, making the PTP reside in much farther proximity to TMP than that in the absence of bacteria. Therefore, much weaker FRET is observed. Interesting, the detection for bacteria based on FRET changes of PTP/TMP complex is visual in view of the color changes under ultraviolet (UV) irradiation. This assay takes advantage of the light-harvesting property of conjugated polymer and the ratiometric measurements for minimizing the nonspecific binding effect. The strategy is promising in pathogen detection in drinking water and other sources.

The conformation of calmodulin (CaM) changes from closed configuration to open one, converting to a claviform dumbbell-shaped biomolecule upon Ca2+-binding. A hybrid probe of graphene oxide (GO) cationic conjugated polymer for detection of the conformation transition of CaM by using FRET technique is demonstrated. The stronger hydrophobic interaction and weaker electrostatic repulsion leads to more CaM adsorption to the surface of GO upon binding with Ca2+ than that of CaM in the absence of Ca2+ (apoCaM), resulting in much farther proximity between poly[(9,9-bis(6-N,N,N-trimethylammonium)hexyl)-fluorenylene phenylene dibromide] (PFP) and green fluorescent protein labeled at the N-terminus of CaM and therefore much weaker FRET efficiency for PFP/Ca2+/CaM in comparison with that of PFP/apoCaM in the presence of GO. Notably, the assembly of CaM with GO is quantitatively and reversibly controlled by Ca2+ ions.

An assembly was fabricated and was revealed to be a multiple-stimulus-responsive biomimetic hybrid polymer architecture. It was constructed by the hydrophobic interactions between a conjugated polyfluorene that contained 2,1,3-benzothiadiazole units (PFBT) and a tri(ethylene glycol)-functionalized polyisocyanopeptide (3OEG-PIC). The introduction of PFBT to the polyisocyanopeptide (PIC) network allowed for the incorporation of responsiveness to multiple stimuli including temperature, CO2 , carbonic anhydrase, and nonlinear mechanics, which mimics natural processes and interactions. Furthermore, the light-harvesting and signal amplification characteristics of PFBT endowed the supramolecular assembly with the essential function of fluorescence monitoring for biological processes.