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A facile fabrication strategy to amplify the inhibitory effects of a nanobody on human islet amyloid polypeptide (IAPP) aggregation by coordinating a metal cation Zn2+ with a histidine-tagged nanobody to form a multivalent nanobody assembly was developed.

Two-dimensional (2D) nanomaterials hold great potential for cancer theranostic applications, yet their clinical translation faces great challenges of high toxicity and limited therapeutic/diagnostic modality. Here, we have created a kind of symbiotic 2D carbon-2D clay nanohybrids, which are composed of a novel 2D carbon nanomaterial (carbon nanochips, or CNC), prepared by carbonizing a conjugated polymer polydiiodobutadiyne, and a 2D layered aluminosilicate clay mineral montmorillonite (MMT). Intriguingly, with the formation of the nanohybrids, MMT can help the dispersion of CNC, while CNC can significantly reduce the hemolysis and toxicity of MMT. The symbiotic combination of CNC and MMT also leads to a synergistic anti-cancer theranostic effect. CNC has a strong absorption and high photothermal conversion efficiency in the second near-infrared region (NIR-II, 1000-1700 nm), while MMT contains Fe

Radiation-induced segregation (RIS) is a typical non-equilibrium process that can dramatically alter the behavior of defect sinks and material properties under irradiation. However, RIS mechanisms have been rarely studied around small He bubbles owing to the technical challenges involved in direct measurements of local chemistry. Here, using state-of-the-art atom probe tomography, we report the RIS behavior near He bubbles in the FeNiCoCr high-entropy alloy that indicates Co segregates most strongly, followed by weaker Ni segregation, whereas Fe and Cr are depleted almost to the same degree. Exceptionally, the magnitude of Co segregation around He bubbles is higher than previously measured values at voids and dislocation loops. Electron energy-loss spectroscopy was used to measure the He density and pressure inside individual bubbles. We demonstrate that He bubbles are over-pressurized at the irradiation temperature that could result in the vacancy bias and the subsequent vacancy-dominated RIS mechanism. First-principles calculations further reveal that there are repulsive interactions between He and Co atoms that may reduce the frequency of Co-vacancy exchange. As a result, He atoms likely retard Co diffusion via the vacancy mechanism and enhance the heterogeneity of RIS in Co-containing multicomponent alloys. These insights could provide the basis for understanding He effects in nuclear materials and open an avenue for tailoring the local chemical order of medium-and high-entropy alloys.

The misfolding and aggregation of human islet amyloid polypeptide (IAPP) into β-sheet-enriched amyloid fibrils is linked to type 2 diabetes. Antibodies are potent inhibitors of IAPP amyloidogenesis, but their preparation is usually complicated and expensive. Here we have created a multivalent antibody mimic SPEPS@Au through conformational engineering of the complementary-determining regions (CDRs) of antibodies on gold nanoparticles (AuNPs). By immobilizing both terminals of an IAPP-recognizing CDR loop (PEP) on the surface of AuNPs, the active conformation of PEP can simply recur on the gold-based antibody mimic, significantly enhancing the binding affinity between PEP and IAPP. SPEPS@Au mitigated amyloidogenesis of IAPP at low sub-stoichiometric concentrations, even after IAPP started aggregating, and dramatically reduced the amyloidogenesis-induced toxicity and ROS production both

Despite being strong with many outstanding physical properties, tungsten is inherently brittle at room temperature, restricting its structural and functional applications at small scales. Here, a facile strategy has been adopted, to introduce high-density dislocations while reducing grain boundaries, through electron backscatter diffraction (EBSD)-guided microfabrication of cold-drawn bulk tungsten wires. The designed tungsten microwire attains an ultralarge uniform tensile elongation of ~10.6%, while retains a high yield strength of ~2.4 GPa. in situ TEM tensile testing reveals that the large uniform elongation of tungsten microwires originates from the motion of pre-existing high-density dislocations, while the subsequent ductile fracture is attributed to crack-tip plasticity and the inhibition of grain boundary cracking. This work demonstrates the application potential of tungsten microcomponents with superior ductility and workability for micro/nanoscale mechanical, electronic, and energy systems.

Ferroptosis is a recently-defined tumor suppression mechanism, but the sensitivity of many tumorigenic cells to ferroptosis is limited by their deficient expression of acyl-CoA synthetase long-chain family member 4 (ACSL4). Here, we report the discovery of a photosensitizer, namely TPCI, which can evoke ACSL4-independent ferroptosis of cancer cells in photodynamic therapy. Through co-localization with 12-lipoxygenase (ALOX12) in multiple subcellular organelles, TPCI activates ALOX12 to generate lipid reactive oxygen species in large quantity and trigger cell ferroptosis. Intriguingly, confining TPCI exclusively in lysosomes switches the cell death from ferroptosis to apoptosis. More strikingly, the ferroptosis mediated by TPCI-induced ALOX12 activation does not require the participation of ACSL4. Therefore, our study identifies TPCI as the first ALOX12 activator to induce ferroptosis independent of ACSL4, which renders a viable therapeutic approach on the basis of distinct ferroptosis of cancer cells, regardless their ACSL4 expressions.

Raman-based super multiplexing has attracted great interest in imaging, biological analysis, identity security, and information storage. It still remains a great challenge to synthesize a large number of different Raman-active molecules to fulfill the Raman color palette. Here, we report a facile and systematic strategy to construct continuously multiplexed ultrastrong Raman probes. By precisely incorporating different ratios of

Despite being the mainstay treatment for many types of cancer in clinic, radiotherapy is undertaking great challenges in overcoming a series of limitations. Radiosensitizers are promising agents capable of depositing irradiation energy and generating free radicals to enhance the radiosensitivity of tumor cells. Combining radiosensitizers with functional polymer-based nanomaterials holds great potential to improve biodistribution, circulation time, and stability in vivo. The derived polymeric nano-radiosensitizers can significantly improve the efficiency of tumor targeting and radiotherapy, and reduce the side effect to healthy tissues. In this review, an overview of functional polymer-based nanomaterials for radiosensitization in recent years is provided. Particular emphases are given to the action mechanisms, drug loading methods, targeting efficiencies, the impact on therapeutic effects, and biocompatibility of various radiosensitizing polymers, which are classified as polymeric micelles, dendrimers, polymeric nanospheres, nanoscale coordination polymers, polymersomes, and nanogels. The challenges and outlooks of polymeric nano-radiosensitizers are also discussed.

Designing and synthesizing new materials with special physical and chemical properties are the key steps to assembling high performance supercapacitors. Metal organic framework (MOF) derived porous carbon materials have drawn great attention in supercapacitors because of their large specific surface area, high chemical/thermal stability and tunable pore structure. Thus, the recent development of porous carbon as an electrode material for supercapacitors is reviewed. The types, design and synthesis strategies of porous carbon are systematically summarized. This review will be divided into three main parts: (1) the design and synthesis of MOF precursors and templates for MOF-derived porous carbon materials; (2) the application of different types of MOF-derived carbon in supercapacitors; and (3) the design of typical structures of porous carbon composites for supercapacitors. Finally, the problems and challenges confronted when using porous carbon are assessed and elaborated, and some suggestions on future research directions are proposed.

Theranostics that integrates therapy and diagnosis in one system to achieve accurate cancer diagnosis and treatment has attracted tremendous interest, and has been recognized as a potential breakthrough in overcoming the challenges of conventional oncotherapy. Nanoparticles are ideal candidates as carriers for theranostic agents, which is attributed to their extraordinary physicochemical properties, including nanoscale sizes, functional properties, prolonged blood circulation, active or passive tumor targeting, specific cellular uptake, and in some cases, excellent optical properties that ideally meet the needs of phototherapy and imaging at the same time. Overall, with the development of nanotechnology, theranostics has become a reality, and is now in the transition stage of "bench to bedside." In this review, we summarize recent progress on nanotechnology-based theranostics, i.e., nanotheranostics, that has greatly assisted traditional therapies, and has provided therapeutic strategies emerging in recent decades, as well as "cocktail" theranostics mixing various treatment modalities.

Summary Recently, gold nanoribbons (Au NRBs) with hexagonal (4H) phase have emerged as a new kind of ultrathin Au nanostructure with unusual metastable crystal phase, which could possess unique physiochemical properties and various promising applications. However, its geometric structure and phase stability under realistic service conditions, like Joule heating or external thermal loading, have not been well studied. Here, we systematically investigated the thermal responses in geometries and crystalline phases of ultrathin 4H Au NRBs under controlled in situ heating. It is found that upon moderate electron beam irradiation heating below 400 K, “Rayleigh instability” can be gradually observed, showing an obvious geometric effect, but the 4H phase remains stable. However, phase transition from 4H to face-centered cubic phases occurs when heating temperature approaches 800 K by using a dedicated microelectromechanical system heating chip, which agrees well with the result obtained by molecular dynamics simulations.

The binary-lipid system of soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO) can hydrate to gels on contacting with aqueous mediums, which has emerged as a versatile and promising delivery matrix for extended drug release applications. In the present work, we have characterized the gelation process of this SPC/GDO lyotropic gel (SGLG) system by rheology and evaluated the drug release profiles from the SGLG formulations with different SPC/GDO mass ratios. Our study has demonstrated that simply adjusting the SPC/GDO mass ratio can tune the lipid gelation behavior and modulate the drug release profiles. More importantly, the drug release from the SGLG formulations follows a two-compartment (fast and slow release compartments) release kinetics that has not been reported before. We posit that the fast release compartment corresponds to the passive diffusion of the drug during the early stage of the gel formation. After the boundary gel phase generation, the drug release is then dominated by the slow diffusion process from SGLG. The pharmacokinetic studies in rats match well with the in vitro studies, suggesting that the binary-lipid formulation is an excellent candidate for on-demand sustained drug delivery system.

As an emerging material for environmental remediation, MoS2 with various dimensional nanostructures has attracted much attention. Herein, a novel C@MoS2/montmorillonite composite material (C@MoS2/MMT) with 3D hierarchical superstructures was successfully prepared via the facile one-step solvothermal growth of MoS2 nanosheets with the assistance of glucose on the surface of montmorillonite (MMT). The structural analysis indicated the formation of a 3D C@MoS2/MMT composite with C and defect-abundant MoS2 embedded on the MMT surface with the presence of amidogen and hydroxyl groups. Consequently, the C@MoS2/MMT composite was subjected for the removal of Pb(II) in aquatic systems and attained a maximum adsorption capacity of 187.0 mg g−1 at 298 K. Additionally, the composite was found to have very high selectivity to Pb(II); it can effectively adsorb approximately 95% of Pb(II) ions in the presence of various competing ions (Cu(II), Zn(II), Cd(II) and Cr(VI)). Furthermore, the structural and morphological characteristics and possible removal mechanisms were intensively explicated in this work. The mechanism study indicated that the enhanced Pb(II) removal was due to electrostatic interactions, surface diffusion and the formation of PbMoO4 on the surface of C@MoS2/MMT. Therefore, this work provides a strategy for efficient environmental remediation to design hybrid nanosheets with diverse heterogeneous 3D structures using earth-abundant transition metal dichalcogenide materials and natural clay minerals.

Photodynamic theranostics integrating synchronous photodynamic therapy and real-time monitoring of therapeutic efficacy has attracted great interest in clinical cancer management. Recently, a series of cationic molecules have been reported as self-reporting photosensitizers for unimolecular photodynamic theranostics. However, the design rationality and mechanisms for such multifunctional photosensitizers are not well understood and need further exploration. In this work, we have designed and synthesized three multicationic AIEgen photosensitizers with similar core structures, but which are end-capped with pyridinium groups (BPCI and TPCI) or quaternary ammonium groups (TPCB), respectively. The tetra-pyridinium-tethered TPCI exhibits superior efficiency in reactive oxygen species generation and dead cell identification compared to both bis-pyridinium-tethered BPCI and tetra-ammonium-tethered TPCB. The structure–activity relationship of all three AIEgens has been studied in detail, which provides great insights into designing the new generation of photosensitizers for photodynamic theranostics. Strikingly, all the multicationic AIEgens have large two-photon absorption cross-sections, and TPCI can effectively kill Caenorhabditis elegans upon white light irradiation and differentiate the dead nematodes from the living ones through the redistribution of its two-photon fluorescence, demonstrating great potential in two-photon fluorescence imaging-guided photodynamic theranostics.

Live-cell Raman imaging based on bioorthogonal Raman probes with distinct signals in the cellular Raman-silent region (1800–2800 cm−1) has attracted great interest in recent years. We report here a class of water-soluble and biocompatible polydiacetylenes with intrinsic ultrastrong alkyne Raman signals that locate in this region for organelle-targeting live-cell Raman imaging. Using a host-guest topochemical polymerization strategy, we have synthesized a water-soluble and functionalizable master polydiacetylene, namely poly(deca-4,6-diynedioic acid) (PDDA), which possesses significantly enhanced (up to ~104 fold) alkyne vibration compared to conventional alkyne Raman probes. In addition, PDDA can be used as a general platform for multi-functional ultrastrong Raman probes. We achieve high quality live-cell stimulated Raman scattering imaging on the basis of modified PDDA. The polydiacetylene-based Raman probes represent ultrastrong intrinsic Raman imaging agents in the Raman-silent region (without any Raman enhancer), and the flexible functionalization of this material holds great promise for its potential diverse applications., Raman probes which operate in the cellular silent region are of interest for live cell imaging. Here, the authors report on the development of a water soluble polydiacetylene Raman probe with enhanced Raman signal in the silent region which can be functionalised for organelle targeting and demonstrate application.

Polydiacetylene (PDA) is a kind of highly conjugated polymer with unique colorimetric and optical properties. A blue and non-fluorescent PDA can be formed upon 254 nm UV irradiation or γ-ray irradiation via 1,4-polymerization of diacetylene monomers, which will transition to red and fluorescent PDA when exposed to environment stimuli, such as pH, temperature, electric and mechanical stresses, and ligand–receptor interactions. As a result, PDA-based materials are particularly attractive for biosensing applications. In addition, the rigid conjugated backbone of PDA derived from its unique topochemical polymerization method also endows exceptional mechanical strength and stability to PDA-based biomaterials, such as liposomes, micelles, and bioscaffolds. The versatility of PDA-based smart materials enables their application in a wide range of biomedical areas. In this review, we briefly summarized the recent progress of biomedical applications of PDA as smart materials in biosensors, drug delivery and bioimaging, as well as tissue engineering. The challenges and outlooks of PDA-based smart materials were also discussed.

Combining immune checkpoint blockade (ICB) therapy with photodynamic therapy (PDT) holds great potential in treating immunologically “cold” tumors, but photo-generated reactive oxygen species (ROS) can inevitably damage co-administered ICB antibodies, hence hampering the therapeutic outcome. Here we create a ROS-responsive hydrogel to realize the sustained co-delivery of photosensitizers and ICB antibodies. During PDT, the hydrogel skeleton poly(deca-4,6-diynedioic acid) (PDDA) protects ICB antibodies by scavenging the harmful ROS, and at the same time, triggers the gradual degradation of the hydrogel to release the drugs in a controlled manner. More interestingly, we can visualize the ROS-responsive hydrogel degradation by Raman imaging, given the ultrastrong and degradation-correlative Raman signal of PDDA in the cellular silent window. A single administration of the hydrogel not only completely inhibits the long-term postoperative recurrence and metastasis of 4T1-tumor-bearing mice, but also effectively restrains the growth of re-challenged tumors. The PDDA-based ROS-responsive hydrogel herein paves a promising way for the durable synergy of PDT and ICB therapy.

Two-photon photodynamic therapy (2P-PDT) that employs photosensitizers (PSs) with 2P absorption is particularly intriguing in cancer treatment, in that 2P excitation enables precise spatial localization and deep tissue penetration. Here, a donor-π-acceptor PS (named TPBPy) with near infrared (NIR) aggregation-induced emission (AIE) is designed and synthesized for imaging-guided 2P-PDT. The maximal photoluminescence (PL) peak of TPBPy is as high as 720 nm when it is encapsulated in liposomes. Upon 2P irradiation by a laser in NIR-II window (λ = 1000 nm), TPBPy exhibits strong NIR-I PL in a multicellular tumor spheroids (MCTSs) model, showing an imaging depth of 210 µm that is significantly higher than upon one-photon irradiation. Moreover, TPBPy localizes specifically on mitochondrion, an important organelle in cell oxidative metabolism and apoptosis. When exposed to the NIR-II irradiation, TPBPy can efficiently generate singlet oxygen (1 O2 ) and trigger cell death. The efficacy of TPBPy-mediated 2P-PDT has also been validated using 4T1 tumor mouse model, the growth of which is significantly suppressed upon NIR-II laser irradiation. TPBPy herein serves as an excellent candidate to suppress deep tumor tissues through NIR-II 2P-PDT, and also renders a new paradigm to construct mitochondrion-anchored AIE luminogens for future cancer theranostic applications.

The development of inhibitors that can effectively mitigate the amyloidogenesis of human islet amyloid polypeptide (hIAPP), which is linked to type II diabetes, remains a great challenge. Oligotyrosines are intriguing candidates in that they can block the hIAPP aggregation through multiplex phenol-hIAPP interactions. However, oligotyrosines containing too many tyrosine units (larger than three) may fail to inhibit amyloidogenesis due to their increased hydrophobicity and strong self-aggregation propensity. In this work, we developed a strategy to hierarchically vitalize oligotyrosines in mitigating hIAPP amyloidogenesis. Tetratyrosine YYYY (4Y) was grafted into the third complementary-determining region (CDR3) of a parent nanobody to construct a sequence-programmed nanobody N4Y, in which the conformation of the grafted 4Y fragment was constrained for a significantly enhanced binding affinity with hIAPP. We next conjugated N4Y to a polymer to approach a secondary vitalization of 4Y through a multivalent effect. Theiin vitro/iandiin vivo/iexperiments validated that the resulting PDN4Y could completely inhibit the hIAPP amyloidogenesis at low stoichiometric concentrations and effectively suppress the generation of toxic reactive oxygen species and alleviate amyloidogenesis-mediated damage to INS-1 cells and zebrafish (iDanio rerio/i) embryos. The hierarchical vitalization of 4Y via a synergistic conformation restraint and multivalent effect represents a strategic prototype of boosting the efficacy of peptide-based amyloidogenesis inhibitors, especially those with a high hydrophobicity and strong aggregation tendency, which holds great promise for future translational studies.

The rapid development of digital society and artificial intelligence has triggered explosive demands for specialty plastics, especially conjugated polymers that are instrumental for flexible electronics and smart devices. The recycling and degradation of postconsumer conjugated polymers have become more important than ever to reduce the pressure to the environment. Here we report the discovery of an environmentally self-degradable conjugated polymer poly(deca-4,6-diynedioic acid), or PDDA. PDDA is stable in the dark or without oxygen when used as a functional material. However, when exposed to sunlight and air after the service life, PDDA disintegrates rapidly and fully decomposes through photooxidation in a week, yielding biocompatible, value-added succinic acid as a major degradation product. The complete degradation of PDDA into green upcycling products by sunlight in air, without leaving any microplastics, not only renders a pioneering paradigm of environmentally self-degradable conjugated polymers but also inspires developing effective strategies to completely degrade postconsumer conjugated polymers in a natural environment.

Locoregional drug delivery has emerged as a promising solution to the problems associated with intravenously administered antitumor agents, such as systemic toxicity and insufficient drug accumulation at tumor sites. Herein, we have developed an adhesive nanoparticle (NP)-based drug delivery system, using natural bioadhesive tannic acid (TA) and metal ions (Fe3+), for locoregional photothermal and antiangiogenic synergistic cancer therapy. In this study, a new near-infrared (NIR) photothermal agent indocyanine green (IR820) and an antiangiogenic agent sorafenib (SRF) were co-encapsulated in a TA-Fe complex (SIF@TA-Fe). The SIF@TA-Fe NPs exhibited super adhesion, antiangiogenesis, and efficient cellular uptake. Moreover, SIF@TA-Fe NPs showed a synergistic antitumor effect in vivo, including high tumor inhibition rate, excellent survival extension, and low risk of recurrence, resulting from the prolonged retention of the NPs in the tumor. Thus, this adhesive SIF@TA-Fe NP-based therapeutic system provides a promising approach for locoregional drug delivery of combined cancer therapy.