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The efficacious delivery of antimicrobial drugs to intractable oral biofilms remains a challenge due to inadequate biofilm penetration and lack of pathogen targeting. Herein, we have developed a microenvironment-activated poly(ethylene glycol) (PEG)-sheddable nanoplatform to mediate targeted delivery of drugs into oral biofilms for the efficient prevention of dental caries. The PEGylated nanoplatform with enhanced biofilm penetration is capable of deshielding the PEG layer under slightly acidic conditions in a PEG chain length-dependent manner to re-expose the bacteria-targeting ligands, thereby facilitating targeted codelivery of ciprofloxacin (CIP) and IR780 to the bacteria after accumulation within biofilms. The nanoplatform tends to induce bacterial agglomeration and suffers from degradation in the acidic oral biofilm microenvironment, triggering rapid drug release on demand around bacterial cells. The self-modulating nanoplatform under near-infrared (NIR) irradiation accordingly displays greatly augmented potency in oral biofilm penetration and disruption compared with drugs alone. Topical oral treatment with nanoplatforms involving synergetic pharmacological and photothermal/photodynamic trinary therapy results in robust biofilm dispersion and efficacious suppression of severe tooth decay in rats. This versatile nanoplatform can promote local accumulation and specific drug transport into biofilms and represents a new paradigm for targeted drug delivery for the management of oral biofilm-associated infections.

Both sulfur and fluorine play important roles in organic synthesis, the life science, and materials science. The direct incorporation of these elements into organic scaffolds with precise control of the oxidation states of sulfur moieties is of great significance. Herein, we report the highly selective electrochemical vicinal fluorosulfenylation and fluorosulfoxidation reactions of alkenes, which were enabled by the unique ability of electrochemistry to dial in the potentials on demand. Preliminary mechanistic investigations revealed that the fluorosulfenylation reaction proceeded through a radical-polar crossover mechanism involving a key episulfonium ion intermediate. Subsequent electrochemical oxidation of fluorosulfides to fluorosulfoxides were readily achieved under a higher applied potential with the adventitious H2O in the reaction mixture.

Стаття присвячена одному з актуальних питань при інвазивних втручаннях — післяопераційному знеболюванню. Наведено дані щодо ефективності планового застосування декскетопрофену (препарат Кейвер) як засобу, що може нівелювати періоди неадекватної аналгезії у травматологічних хворих, які перенесли ендопротезування кульшового суглоба. Доведено, що застосування декскетопрофену в схемі премедикації та у складі мультимодальної аналгезії в післяопераційному періоді у травматологічних хворих дозволяє досягти більш якісного знеболювання порівняно з аналгезією «за потребою» опіатами чи іншими нестероїдними протизапальними засобами, а також вагомо знизити потреби в наркотичних анальгетиках в післяопераційному періоді (зі 100 до 29,6 %).

The outcome of sonodynamic immunotherapy is significantly limited by tumor hypoxia. To overcome this obstacle, one common solution is to catalyze the conversion of endogenous H2O2 into O2. However, the effectiveness of this strategy is limited by the insufficient concentration of H2O2 in the tumor microenvironment (TME). Herein, we developed a H2O2 economizer for on-demand O2 supply and sonosensitizer-mediated reactive oxygen species production during ultrasound activation, thereby alleviating hypoxia-associated limitations and augmenting the efficacy of sonodynamic immunotherapy. Methods: The H2O2 economizer is constructed by electrostatic adsorption and π-π interactions between the Fe-doped polydiaminopyridine (Fe-PDAP) nanozyme and chlorin e6. By employing a biomimetic engineering strategy with cancer cell membranes, we addressed the premature leakage issue and increased tumor-site accumulation of nanoparticles (membrane-coated Fe-PDAP/Ce6, MFC). Results: The prepared MFC could significantly attenuate the catalytic activity of Fe-PDAP by reducing their contact with H2O2. Ultrasound irradiation promoted MFC dissociation and the exposure of Fe-PDAP for a more robust O2 supply. Moreover, the combination of MFC-enhanced sonodynamic therapy with anti-programmed cell death protein-1 antibody (aPD-1) immune checkpoint blockade induced a strong antitumor response against both primary tumors and distant tumors. Conclusion: This as-prepared H2O2 economizer significantly alleviates tumor hypoxia via reducing H2O2 expenditure and that on-demand oxygen-elevated sonodynamic immunotherapy can effectively combat tumors.

Creation of scaffold-based tissue-engineered constructs (SB TECs) is costly and requires coordinated qualified efforts. Cryopreservation enables longer shelf-life for SB TECs while enormously enhancing their availability as medical products. Regenerative treatment with cryopreserved SB TECs prepared in advance (possibly pret-a-porter) can be started straight away on demand. Animal studies and clinical trials indicate similar levels of safety for cryopreserved and freshly prepared SB TECs. Although cryopreservation of such constructs is more difficult than that of cell suspensions or tissues, years of research have proved the principal possibility of using ready-to-transplant SB TECs after prolonged cryostorage. Cryopreservation efficiency depends not only on the sheer viability of adherent cells on scaffolds after thawing, but largely on the retention of proliferative and functional properties by the cells, as well as physical and mechanical properties by the scaffolds. Cryopreservation protocols require careful optimization, as their efficiency depends on multiple parameters including cryosensitivity of cells, chemistry and architecture of scaffolds, conditions of cell culture before freezing, cryoprotectant formulations, etc. In this review we discuss recent achievements in SB TEC cryopreservation as a major boost for the field of tissue engineering and biobanking.

Protein nanocages play crucial roles in sub-cellular compartmentalization and spatial control in all domains of life and have been used as biomolecular tools for applications in biocatalysis, drug delivery, and bionanotechnology. The ability to control their assembly state under physiological conditions would further expand their practical utility. To gain such control, we introduced a peptide capable of triggering conformational change at a key structural position in the largest known encapsulin nanocompartment. We report the structure of the resulting engineered nanocage and demonstrate its ability to on-demand disassemble and reassemble under physiological conditions. We demonstrate its capacity for in vivo encapsulation of proteins of choice while also demonstrating in vitro cargo loading capabilities. Our results represent a functionally robust addition to the nanocage toolbox and a novel approach for controlling protein nanocage disassembly and reassembly under mild conditions.

Glipizide and glibenclamide remain some of the widely prescribed antidiabetic sulfonylurea drugs for the treatment of type 2 diabetes mellitus. Herein the authors report on an isocyanate-free synthetic procedure towards the preparation of these on demand drugs at multigram scale using continuous flow technology. The safety concern over the use of isocyanates in most of the existing synthetic routes was dealt with in this present work by using N-carbamates synthesised in situ from activation of amines with chloroformates as safer alternatives. An overall yield of 80-85 % was obtained for the semi-telescoped steps within 10 min total residence time.

The hydrolysis of aluminum (Al) is a relatively simple method for on-demand hydrogen generation for niche (low-power

Unlike conventional subtractive methods, 3D printing allows rapid prototyping and customization on demand. However, as a process recently applied to carbon-based materials, 3D printing faces many challenges, including the precise tailoring of the printed material and the control of its porosity, as well as obtaining directly printed (pure) carbon. The present review focuses on the latest advances in carbonaceous materials in 3D printing to address these challenges. A brief introduction to additive manufacturing processes is given, followed by a summary and many recent examples of manufacturing processes, structural characteristics, and applications of various carbon-based composites and carbonaceous materials. Finally, viewpoints and prospects for this emerging field are presented.

"On-demand" accurate imaging of multiple intracellular miRNAs will significantly improve the detection reliability and accuracy. However, the "always-active" design of traditional multicomponent detection probes enables them to passively recognize and output signals as soon as they encounter targets, which will inevitably impair the detection accuracy and, inevitably, result in false-positive signals. To address this scientific problem, in this work, we developed a near-infrared (NIR) light-activated multicomponent detection intelligent nanoprobe for spatially and temporally controlled on-demand accurate imaging of multiple intracellular miRNAs. The proposed intelligent nanoprobe is composed of a rationally designed UV light-responsive triangular DNA nano sucker (TDS) and upconversion nanoparticles (UCNPs), named UCNPs@TDS (UTDS), which can enter cells autonomously through endocytosis and enable remote regulation of on-demand accurate imaging for multiple intracellular miRNAs using NIR light illumination at a chosen time and place. It is worth noting that the most important highlight of the UTDS we designed in this work is that it can resist nonspecific activation as well as effectively avoid false-positive signals and improve the accuracy of imaging of multiple intracellular miRNAs. Moreover, distinguishing different kinds of cell lines with different miRNA expressions levels can be also achieved through this NIR light-activated intelligent UTDS, showing feasible prospects in precise imaging and disease diagnosis.

The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics. Bacterial infections are detrimental to our life and health. To reduce the abuse of antibiotics and treat biofilm-related bacterial infections, a biomimetic nano-antibacterial system, RBCM-NW-G namely, that controls the release of antibiotics through near infrared was prepared. The hollow porous structure and the high surface activity of nanoworms are used to realize antibiotic loading, and then, biomimetics are applied with red blood cell membranes (RBCM). RBCM-NW-G, which retains the performance of RBCM, shows enhanced permeability and retention effects. Fluorescence imaging in mice showed the effective accumulation of RBCM-NW-G at the site of infection. In addition, the biomimetic nanoparticles showed a longer blood circulation time and good biocompatibility. Anti-biofilm test results showed damage to biofilms due to a photothermal effect and a highly efficient antibacterial performance under the synergy of the photothermal effect, silver iron, and antibiotics. Finally, by constructing a mouse infection model, the great potential of RBCM-NW-G in the treatment of in vivo infections was confirmed., Highlights • A new biomimetic nanosystem was developed for treating bacterial infections in vivo. • The model used near-infrared irradiation to cause damage to biofilms. • A highly efficient antibacterial performance was detected. • This nanosystem achieved a controllable and efficient use of antibiotics.

Strained alkenes and alkynes are the predominant dienophiles used in inverse electron demand Diels–Alder (IEDDA) reactions. However, their instability, cross-reactivity, and accessibility are problematic. Unstrained dienophiles, although physiologically stable and synthetically accessible, react with tetrazines significantly slower relative to strained variants. Here we report the development of potassium arylethynyltrifluoroborates as unstrained dienophiles for fast, chemically triggered IEDDA reactions. By varying the substituents on the tetrazine (e.g., pyridyl- to benzyl-substituents), cycloaddition kinetics can vary from fast (k2 = 21 M–1 s–1) to no reaction with an alkyne-BF3 dienophile. The reported system was applied to protein labeling both in the test tube and fixed cells and even enabled mutually orthogonal labeling of two distinct proteins.

In only a few decades, lithium-ion batteries have revolutionized technologies, enabling the proliferation of portable devices and electric vehicles1, with substantial benefits for society. However, the rapid growth in technology has highlighted the ethical and environmental challenges of mining lithium, cobalt and other mineral ore resources, and the issues associated with the safe usage and non-hazardous disposal of batteries2. Only a small fraction of lithium-ion batteries are recycled, further exacerbating global material supply of strategic elements3–5. A potential alternative is to use organic-based redox-active materials6–8 to develop rechargeable batteries that originate from ethically sourced, sustainable materials and enable on-demand deconstruction and reconstruction. Making such batteries is challenging because the active materials must be stable during operation but degradable at end of life. Further, the degradation products should be either environmentally benign or recyclable for reconstruction into a new battery. Here we demonstrate a metal-free, polypeptide-based battery, in which viologens and nitroxide radicals are incorporated as redox-active groups along polypeptide backbones to function as anode and cathode materials, respectively. These redox-active polypeptides perform as active materials that are stable during battery operation and subsequently degrade on demand in acidic conditions to generate amino acids, other building blocks and degradation products. Such a polypeptide-based battery is a first step to addressing the need for alternative chemistries for green and sustainable batteries in a future circular economy. An environmentally friendly, all-organic radical battery is demonstrated, in which redox-active polypeptides perform as both cathode and anode materials, with a metal-free organic electrolyte.

Portable devices capable of rapid disease detection and health monitoring are crucial to decentralizing diagnostics from clinical laboratories to the patient point-of-need. Although technologies have been developed targeting this challenge, many require the use of reporter molecules or reagents that complicate the automation and autonomy of sensors. New work in the field has targeted reagentless approaches to enable breakthroughs that will allow personalized monitoring of a wide range of biomarkers on demand. This Perspective focuses on the ability of reagentless platforms to revolutionize the field of sensing by allowing rapid and real-time analysis in resource-poor settings. First, we will highlight advantages of reagentless sensing techniques, specifically electrochemical detection strategies. Advances in this field, including the development of wearable and in situ sensors capable of real-time monitoring of biomarkers such as nucleic acids, proteins, viral particles, bacteria, therapeutic agents, and metabolites, will be discussed. Reagentless platforms which allow for wash-free, calibration free-detection with increased dynamic range are highlighted as a key technological advance for autonomous sensing applications. Furthermore, we will highlight remaining challenges which must be overcome to enable widespread use of reagentless devices. Finally, future prospects and potential breakthroughs in precision medicine that will arise as a result of further development of reagentless sensing approaches are discussed.

Theranostic nanoprobes can potentially integrate imaging and therapeutic capabilities into a single platform, offering a new personalized cancer diagnostic tool. However, there is a growing concern that their clinical application is not safe, particularly due to metal-containing elements, such as the gadolinium used in magnetic resonance imaging (MRI). We demonstrate for the first time that the photothermal melting of the DNA duplex helix was a reliable and versatile strategy that enables the on-demand degradation of the gadolinium-containing MRI reporter gene from polydopamine (PDA)-based theranostic nanoprobes. The combination of chemotherapy (doxorubicin) and photothermal therapy, which leads to the enhanced anti-tumor effect. In vivo MRI tracking reveals that renal filtration was able to rapidly clear the free gadolinium-containing MRI reporter from the mice body. This results in a decrease in the long-term toxic effect of theranostic MRI nanoprobes. Our findings may pave the way to address toxicity issues of the theranostic nanoprobes.

Chlorination with chlorine is straightforward, highly reactive, and versatile, but it has significant limitations. In this Letter, we introduce a protocol that could combine the efficiency of electrochemical transformation and the high reactivity of chlorine. By utilizing Cl3CCN as the chloride source, donating up to all three chloride atom, the reaction could generate and consume the chlorine in situ on demand to achieve the chlorination of aromatic compounds and electrodeficient alkenes.

Fluorophores that respond to external stimuli on demand have numerous applications in imaging and chemical or biological sensing. In this paper, we describe conjugated polymer nanoparticles (CPNs) ...

Emerging chemical techniques for preparation of modern 2D materials lead inevitably to broadening the areas of practical applications on demand of the materials. One of the most bright trends in research and development of the most famous 2D material, graphene oxide, involves the search for optimal mass production, optimization and flexible adjustment of membrane materials for various practical needs as always based on unique structural and chemical features of graphene oxide itself. Here, physical chemical correlations between preparation history, structural peculiarities of graphene oxide and functional properties of graphene oxide-based membranes are reviewed and analyzed.

We investigated the patterning of organic light-emitting diodes using a blue laser irradiation after making uniform device. Laser patterning was carried out in the atmosphere after the organic laye...

In a rapidly changing environment, such as the current COVID-19 pandemic, continuous flow reactors bear the potential to increase the production of urgently needed active pharmaceutical ingredients (APIs) on demand In the synthesis of remdesivir, the organometallic C-glycosylation step was identified as a limitation for the large-scale production, requiring long addition periods and cryogenic temperatures Previous studies have focused on a Grignard-based protocol, but a flash chemistry approach, using organolithium reagents, has facilitated significant improvements After gaining further understanding of the C-glycosylation, this step was successfully transferred to a five-stream continuous flow process, achieving 60% yield at a moderate temperature (−30 °C) in a total residence time of just 8 s Stable processing was demonstrated for 2 h, providing an exceptionally high space−time yield of 10 4 kg L−1 h−1, in a scalable flow reactor system © XXXX American Chemical Society

Stimuli-responsive temporary adhesives constitute a rapidly developing class of materials defined by the modulation of adhesion upon exposure to an external stimulus or stimuli. Engineering these materials to shift between two characteristic properties, strong adhesion and facile debonding, can be achieved through design strategies that target molecular functionalities. This perspective reviews the recent design and development of these materials, with a focus on the different stimuli that may initiate debonding. These stimuli include UV light, thermal energy, chemical triggers, and other potential triggers, such as mechanical force, sublimation, electromagnetism. The conclusion discusses the fundamental value of systematic investigations of the structure–property relationships within these materials and opportunities for unlocking novel functionalities in future versions of adhesives., Stimuli-responsive temporary adhesives emerge as next-generation multifunctional materials with advantages that include strong temporary adhesion, debonding on demand, and tunable reactivity.

Poor cellular uptake and slow intracellular drug release remain the main barriers for the efficient application of micellar delivery system. Taking advantage of the overexpressed CD44 receptor and mild acidic microenvironment of tumour cells, CD44-targeted pH-responsive micelles based on the self-assembly of histidine-hyaluronic acid-dodecylamine (His-HA-DA) were prepared for the delivery of doxorubicin (DOX). These micelles exhibited pH-responsive behaviour with increased particle size, decreased encapsulation efficiency (EE%) of DOX and rapid release of DOX triggered by low pH. Compared with free DOX, DOX/HHD exhibited relatively high cellular uptake mainly

Local delivery of drugs, proteins and living cells with on demand release manner using porous scaffolds has been widely used in the field of tissue engineering and cancer therapies. Drugs directly loaded in the porous scaffolds, are generally prone to free diffuse especially for long term incubation. Herein, in this study, hollow fiber alginate/iron oxide nanoparticles scaffolds were prepared by coaxial 3D printing with drugs, protein or living cells encapsulating in the core part (low concentration of alginate gels). Magnetically-driven on demand release was realized by extruding the loaded drugs, proteins and cells from the core part of the hollow fibers due to the deformation of the scaffolds under magnetic field. Additionally, the hollow fibers could sever as diffusion barriers to reduce uncontrolled diffusion of drugs, proteins and cells from scaffolds in the conditions of no required stimulation. The factors influencing the deformation of the scaffolds, as well as the release behavior were investigated. The data indicated that the scaffolds prepared by 10 wt% of alginate with 13% of iron oxide nanoparticles after crosslinking using 0.1 M CaCl2 solution for 10 s showed repeated on demand release capability in vitro and in vivo under intermittently magnetic stimulation. Thus, this 3D printed alginate/iron oxide nanoparticles hollow scaffolds with on demand controlled delivery capability may prove useful for tissue engineering and disease therapies.

Currently, the in situ on/off switch of PTT/PDT reagents for tumor treatment has evoked considerable interest in the field of cancer therapy. However, the actual PTT/PDT therapy efficacy in tumor treatment is largely restricted by the PTT/PDT reagents' aggregation issues during their release from the hydrophobic carrier to the hydrophilic tumor microenvironment. Thus, it remains a challenge to break through the therapy barrier caused by the PTT/PDT agent aggregation and achieve substantial improvement of anticancer efficacy. In this work, we developed a novel near-infrared (NIR) light-responsive and gas bubble-generated liposomal nanobomb (Cy/Ce6/CO2-Lip-FA) through the co-encapsulation of PTT/PDT reagents with gas precursor into the hydrophobic and hydrophilic regions of liposomes, respectively, in order to overcome the aggregation issues and substantially improve the synergistic PTT/PDT efficacy. Upon arrival at the tumor region, the PS phototoxicity of Cy/Ce6/CO2-Lip-FA could be effectively switched on through CO2 generation induced by the PTT effect of Cypate upon NIR irradiation. The gas bubble burst can remarkably suppress the aggregation of Cypate/Ce6 and extremely enhance the synergistic PTT/PDT efficacy. These results indicate that the proposed NIR-responsive and gas bubble-functionalized liposomal nanobomb is a highly promising platform for tumor treatment with better therapeutic efficacy.

Due to their high stability and specificity in living cells, fluorescently labeled nanobodies are perfect probes for visualizing intracellular targets at an endogenous level. However, intrabodies bind unrestrainedly and hence may interfere with the target protein function. Here, we report a strategy to prevent premature binding through the development of photo-conditional intrabodies. Using genetic code expansion, we introduce photocaged amino acids within the nanobody-binding interface, which, after photo-activation, show instantaneous binding of target proteins with high spatiotemporal precision inside living cells. Due to the highly stable binding, light-guided intrabodies offer a versatile platform for downstream imaging and regulation of target proteins.

Polycyclic iridaaromatic compounds are of great interest not only because of the contributions made in "aromatic chemistry", but also because of the possibility of improving the results of the applications of the corresponding organic analogues in different fields. Therefore, understanding the requirements necessary to build on demand this type of compound with specific properties is of great importance. In this work, the keys to successfully synthesize iridaaromatic complexes via methoxyalkenylcarbenes are established. Experimental and theoretical results show (i) that bearing two aromatic substituents on the gamma carbon of the methoxyalkylcarbene promotes the C-H bond activation; (ii) the need for large steric hindrance of the second substituent for a selective synthesis and, (iii) the selectivity in the C-H bond activation towards the less sterically hindered system.

A continuous flow process to generate [1.1.1]propellane on demand is presented rendering solutions of [1.1.1]propellane that can directly be derivatised into various bicyclo[1.1.1]pentane (BCP) species. This was realised in throughputs up to 8.5 mmol h-1 providing an attractive and straightforward access to gram quantities of selected BCP building blocks. Lastly, a continuous photochemical transformation of [1.1.1]propellane into valuable BCPs bearing mixed ester/acyl chloride moieties was developed.

Currently, no dressings utilized in burn clinics provide adhesion, hydration or mechanical strength on the same order as human skin as well as the ability to be atraumatically removed. We report the synthesis, characterization, and in vivo evaluation of in situ polymerized and subsequent dissolvable hydrogels as burn wound dressings. Hydrogel dressings, from a small library of synthesized materials form in situ, exhibit storage moduli between 100-40,000 Pa, dissolve on-demand within 10 minutes to 90 minutes, swell up to 350%, and adhere to both burned and healthy human skin at 0.2-0.3N/cm(2). Further, results from an in vivo porcine second degree burn model demonstrate functional performance with healing equivalent to conventional treatments with the added benefit of facile, in situ application and subsequent removal via dissolution.

Drop-on-demand microkits with a diameter of ∼20 μm are used to measure the activity of acetylcholinesterase (AChE) in a brain slice with single-cell resolution. The relative standard deviation from 25 cellular regions reached 73.3% exhibiting the difference of enzyme activity in the brain slice. Therefore, this approach utilizing the well-established kits provides an alternative single-cell-resolved strategy for the elucidation of enzymatic heterogeneity at the tissue level.

Singlet oxygen is a short half-life cytotoxic agent which can be generated by chemical and photochemical methods. In order to make use of its antibacterial action at a selected location, it is desirable to have singlet oxygen in a relatively stable, “caged” structure, in the form of an endoperoxide. Here, the trimethylsilyl (TMS) group supplies the steric bulk, inhibiting the cycloreversion reaction to produce very little singlet oxygen under ambient conditions. However, when fluoride ions are added as tetrabutylammonium fluoride, very rapid removal of the TMS group takes place, followed by the unhindered cycloreversion, releasing singlet oxygen much faster. The bactericidal action on surfaces was demonstrated using E. coli, and imaged under fluorescence microscopy. Considering the issues related to emergence of antibiotic resistant bacterial strains, “on demand singlet oxygen” appears to be an exciting alternative.

We have developed a convenient development-scale reactor (0.44 mol/h) to prepare diazomethane from N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) in ∼80% yield. Diazomethane (CH2N2) made with this ...

The softness of nanohydrogels results in unique properties and recently attracted tremendous interest due to the multi‐functionalization of interfaces. Herein, we study extremely soft temperature‐sensitive ultra‐low cross‐linked (ULC) nanogels adsorbed to the solid/water interface by atomic force microscopy (AFM). The ultra‐soft nanogels seem to disappear in classical imaging modes since a sharp tip fully penetrates these porous networks with very low forces in the range of steric interactions (ca. 100 pN). However, the detailed evaluation of Force Volume mode measurements allows us to resolve their overall shape and at the same time their internal structure in all three dimensions. The nanogels exhibit an extraordinary disk‐like and entirely homogeneous but extremely soft structure—even softer than polymer brushes. Moreover, the temperature‐sensitive nanogels can be switched on demand between the ultra‐soft and a very stiff state., Extremely soft temperature‐sensitive nanogels adsorbed to the solid/water interface were studied by atomic force microscopy. The ultra‐soft nanogels disappeared in the classical 2D height image. By detailed analysis of Force Volume data the extraordinary disk‐like and entirely homogeneous but extremely soft structure of the nanogels was resolved.

Background Hypoxia is an important factor that contributes to chemoresistance and metastasis in triple negative breast cancer (TNBC), and alleviating hypoxia microenvironment can enhance the anti-tumor efficacy and also inhibit tumor invasion. Methods A near-infrared (NIR) responsive on-demand oxygen releasing nanoplatform (O2-PPSiI) was successfully synthesized by a two-stage self-assembly process to overcome the hypoxia-induced tumor chemoresistance and metastasis. We embedded drug-loaded poly (lactic-co-glycolic acid) cores into an ultrathin silica shell attached with paramagnetic Gd-DTPA to develop a Magnetic Resonance Imaging (MRI)-guided NIR-responsive on-demand drug releasing nanosystem, where indocyanine green was used as a photothermal converter to trigger the oxygen and drug release under NIR irradiation. Results The near-infrared responsive on-demand oxygen releasing nanoplatform O2-PPSiI was chemically synthesized in this study by a two-stage self-assembly process, which could deliver oxygen and release it under NIR irradiation to relieve hypoxia, improving the therapeutic effect of chemotherapy and suppressed tumor metastasis. This smart design achieves the following advantages: (i) the O2 in this nanosystem can be precisely released by an NIR-responsive silica shell rupture; (ii) the dynamic biodistribution process of O2-PPSiI was monitored in real-time and quantitatively analyzed via sensitive MR imaging of the tumor; (iii) O2-PPSiI could alleviate tumor hypoxia by releasing O2 within the tumor upon NIR laser excitation; (iv) The migration and invasion abilities of the TNBC tumor were weakened by inhibiting the process of EMT as a result of the synergistic therapy of NIR-triggered O2-PPSiI. Conclusions Our work proposes a smart tactic guided by MRI and presents a valid approach for the reasonable design of NIR-responsive on-demand drug-releasing nanomedicine systems for precise theranostics in TNBC. Graphical Abstract

Repeatedly changing dressings during wound healing can cause unbearable physical pain for patients with chronic skin injury. In this study, we designed a tough hydrogel-based dressing that can be degraded in an on-demand fashion for advanced chronic wound care. The resultant hydrogel dressing could be rapidly dissolved within 100 s after wetting with lithium phenyl(2,4,6-trimethylbenzonyl)phosphinate solution under low-power (1 W) ultraviolet (UV) irradiation (365 nm) owing to the breakage of disulfide bonds. This UV-triggered on-demand dissolution of tough hydrogels allows for a facile dressing replacement without causing tissue damage or pain, which is of great potential for clinical utilization.

Biofilm-associated infections are difficult to treat in the clinics because the bacteria embedded in biofilm are ten to thousand times more resistant to traditional antibiotics than planktonic ones. Here, a smart hydrogel comprised of aminoglycoside antibiotics, pectinase, and oxidized dextran was developed to treat local biofilm-associated infections. The primary amines on aminoglycosides and pectinase were reacted with aldehyde groups on oxidized dextran via a pH-sensitive Schiff base linkage to form the hydrogel. Upon bacterial infection, the increased acidity triggers the release of both pectinase and aminoglycoside antibiotics. The released pectinase efficiently degrades extracellular polysaccharides surrounding the bacteria in biofilm, and thus greatly sensitizes the bacteria to aminoglycosides. The smart hydrogel efficiently eradicated biofilms and killed the embedded bacteria both n tvitro and in vivo. This study provides a promising strategy for the treatment of biofilm-associated infections.

The article presents the results of the treatment of 60 patients with premature ejaculation in combination with erectile dysfunction. Patients were divided into three groups, in which patients were prescribed non-drug treatment, or sildenafil 50 mg on demand, or sildenafil 50 mg on demand in combination with melatonin 3 mg at night. Duration of treatment was 6 months. The psychoemotional status, quality of life, quality and duration of intercourse, erectile function and chrono-rhythms of patients were assessed. The results of the study showed that treatment with sildenafil in combination with melatonin was the most clinically effective, which manifested in prolongation of sexual intercourse, improvement of the quality of erection and normalization of the chronobiological status of patients.

A large quantity of oil spills occurred have greatly endangered the natural environment and human survival health. Super-wetting materials with switchable wettability provide a good way to solve these problems efficiently and have been paid more and more attention. In this paper, we have successfully prepared an ethanol-triggered and highly stable superamphiphobic material with a switchable surface wettability by using zinc oxide (ZnO) particles and organic silane (PFDS) via a simple coating method. The superamphiphobic material can maintain high oil-repellent and water-repellent performances under various harsh conditions. Most importantly, the superamphiphobic material demonstrates the switchable wettability by ethanol treatment. In view of this fresh mechanism, it can separate various oil–water mixtures on-demand with high separation efficiency and flux. Surprisingly, the mixtures of highly corrosive liquids and oils can also be separated. In addition, the material also has excellent self-cleaning and anti-fouling capabilities and low surface adhesion, which can effectively avoid the pollution of pollutants in the air. All these advantages show that the as-prepared material can play a vital function in solving the related severe conditions of marine oil pollution and industrial wastewater.

The ability of a cationic coordination cage to encapsulate molecular guests is enhanced by non-covalent capping of the cage portals with tripodal anions. The capped cage provides new cation binding sites at the portals, which enable accommodation of cationic substrates within the cationic cage. In addition, non-covalent capping allows neutral guests in the cage to be exchanged for cationic ones on demand.

There has been an increased interest in the use of protein therapeutics, especially antibodies, for the treatment of a variety of diseases due to their high specificity to tissues and biological pathways of interest. However, the use of antibodies can be hindered by physical aggregation, degradation, and diffusion when injected in vivo leading to the need for antibody-releasing depots for the controlled and localized delivery within tissues of interest. Here, we investigated photolabile hydrogel chemistries for creating on-demand and tunable antibody release profiles. Innovative, scalable synthetic procedures were established and applied for fabricating hydrogels with nitrobenzyl (NB) and coumarin (CMR) photolabile crosslinks that responded to clinically relevant doses of long-wavelength UV and short-wavelength visible light. This synthetic procedure includes a route to make a CMR linker possessing two functional handles at the same ring position with water-stable bonds. The photocleavage properties of NB and CMR crosslinked hydrogels were characterized, as well as their potential for translational studies by degradation through pig skin, a good human skin mimic. The mechanism of hydrogel degradation, bulk versus surface eroding, was determined to be dependent on the wavelength of light utilized and the molar absorptivity of the different photolabile linkers, providing a facile means for altering protein release upon hydrogel degradation. Further, the encapsulation and on-demand release of a model monoclonal antibody was demonstrated, highlighting the ability to control antibody release from these hydrogels through the application of light while retaining its bioactivity. In particular, the newly designed CMR hydrogels undergo surface erosion-based protein release using visible light, which is more commonly used clinically. Overall, this work establishes scalable syntheses and relevant pairings of formulation-irradiation conditions for designing on-demand and light-responsive material systems that provide controlled, tunable release of bioactive proteins toward addressing barriers to preclinical translation of light-based materials and ultimately improving therapeutic regimens.

Adhesive bonding is a viable technique for joining a wide range of materials (e.g. metals, polymers, ceramics, etc., and combinations of any of these materials). However, one disadvantage of adhesive bonding is the permanent character of the joint. In many situations, it is desirable that the joint can be separated so that the materials can be reused on a qualitatively high level. Nowadays, due to the significant pressure on reducing costs and increasing demand for material recyclability, the development of new techniques and processes for easy recycle and repair of bonded structures is becoming of great interest for the industry. This review presents the recent developments in the use of debonding techniques and summarizes the different strategies and approaches used for adhesive debonding. The use of reversible (reworkable) adhesive systems and electrically debondable adhesives is presented. Next, the use of fillers in the adhesive which can be triggered by an external stimulus (e.g. heat: thermal and induction, electrical or magnetic flux) to induce mechanical separation of the substrates is discussed. It is concluded that there is no universally accepted debonding method due to the wide variety of adhesive bonded joint systems and applications. The selection of the appropriate debonding technique will depend on the particular application needs and constraints.

Controllable molecular release from delivery vehicles is essential to successfully reduce drug toxicity and improve therapeutic efficacy. Light-powered hydrophobic molecular motors were therefore incorporated in liposomes to use molecular rotation to facilitate on-demand release. The extent of the release was precisely controlled by irradiation times, providing a simple yet sophisticated responsive molecular nanocarrier. This journal is

Nanoreactors, in which the reactions are remotely controlled by magnetic fields, are potentially valuable in bioorthogonal chemistry for future applications. Here, we develop a silica-confined magnetothermia-induced nanoreactor (MAG-NER) by selectively growing Pd nanocrystals on a preinstalled iron-oxide core inside a hollow silica nanoshell. The growth is achieved by magnetic induction. The interfacial catalytic site is activated by stimulating localized magnetothermia, and nanocompartmentalization is realized by the size-selective porous silica. Therefore, MAG-NER can be conveniently used in complex biomedia and can even be internalized to living cells, realizing an on-demand, high-performance intramolecular carbocyclization reaction by remote operation without compromising the cell viability. This work opens avenues for the design of advanced nanoreactors that complement and augment the existing bioorthogonal chemical tools.

Significance Wirelessly controlled, multitasking soft devices active in aqueous environments are highly required for applications in microfluidics and organ-on-a-chip and as medical devices. Inspired by marine organisms, we present an approach to achieve such devices by utilizing stimuli-responsive material assemblies capable of untethered object manipulation in an enclosed aqueous environment. Our soft robot assembly integrates a magnetically controlled stem with a light-responsive gripper with unmatched speed, insensitivity to contaminants, and high control of actuation underwater at low light intensities. The independent device segments can be orthogonally controlled to realize different tasks such as attracting, capturing, and releasing targets in an aqueous environment, demonstrating the significance of actuator assemblies in the fabrication of multifunctional soft devices operating underwater., The development of light-responsive materials has captured scientific attention and advanced the development of wirelessly driven terrestrial soft robots. Marine organisms trigger inspiration to expand the paradigm of untethered soft robotics into aqueous environments. However, this expansion toward aquatic soft robots is hampered by the slow response of most light-driven polymers to low light intensities and by the lack of controlled multishape deformations. Herein, we present a surface-anchored artificial aquatic coral polyp composed of a magnetically driven stem and a light-driven gripper. Through magnetically driven motion, the polyp induces stirring and attracts suspended targets. The light-responsive gripper is sensitive to low light intensities and has programmable states and rapid and highly controlled actuation, allowing the polyp to capture or release targets on demand. The artificial polyp demonstrates that assemblies of stimuli-responsive materials in water utilizing coordinated motion can perform tasks not possible for single-component devices.

Insulin fibrillation poses a variety of problems in biomedical and biotechnological applications of insulin. Inhibiting insulin fibrillation is highly on demand to address those problems. We herein demonstrate the capability of amphiphilic sulfonatocalixarene to inhibit insulin fibrillation. The amphiphilic assembly of p-sulfonatocalix[4]arene tetra dodecyl ether exhibits much better efficiency on inhibiting insulin fibrillation, with respect to p-sulfonatocalix[4]arene and sodium dodecyl benzenesulphonate. The pronounced inhibition effect results from both the preorganized scaffold of calixarene and the amphiphilic assembly.

The tumour site-specific stimulus responsiveness of smart drug delivery systems gives a unique system for effective therapeutic delivery with reduced toxic effects of conventional chemotherapeutic drugs. In this work, matrix metalloproteinase-2 (MMP-2)-responsive mesoporous silica nanoparticles (MSNs) were synthesized and assessed for "self-actuating" on-demand controlled drug delivery for cancer therapy. MMPs are members of protease enzymes that are generally overexpressed in cancerous tissues in all stages of cancer. MSNs have attracted significant consideration as a potential delivery system because of their robust and versatile physicochemical properties suitable to deliver the therapeutic payload. Cisplatin (Cis) was used as a model drug, which was incorporated into MSNs to evaluate targeting of lung cancer cells and their release kinetics. In this delivery system, collagen was coated on the surface of Cis-loaded MSNs (Cis-MSN) to form a capping layer, resulting in collagen-coated MSNs (Cis-col-MSN). Under normal cell conditions, a collagen-capping coat efficiently forbids the release of Cis molecules from Cis-col-MSN. The tumor microenvironment would lead to augmented drug release because of the uncapping of collagen from MSN pores due to the presence of overexpressed MMP-2 enzyme and the ensuing controlled drug release. MMP-responsive experiments have shown augmented enzyme triggered drug release. The cellular uptake and cytocompatibility studies in A549 adenocarcinomic lung cancer cell lines demonstrated that this nanocarrier could be efficiently endocytosed in 24 h and have shown favorable biocompatibility with the cells. Cytotoxicity results of Cis-col-MSN demonstrated dose-dependent toxicity. The efficacy of the Cis-col-MSN significantly enhanced with the supplementation of MMP-2 enzyme with increasing concentrations in the cell culture milieu. The efficacy of formulation was attributed to significantly enhance reactive oxygen species, cell cycle arrest, and apoptosis. It is expected that Cis-col-MSN promises a pragmatic approach to constructing an "on-demand" smart drug delivery system to deliver a therapeutic payload at the tumor site only.

Gold nanostars (AuNS) are promising carriers for targeted delivery of therapeutic oligonucleotides, but their potential in fabricating an on-demand drug release system in a facile and robust way remains to be explored. In this paper, we used a model aptamer (HApt), acting not only as a target ligand but also as a natural thermal-responsive material, to decorate AuNS. The prepared gold nanoconstruct, HApt@AuNS, displayed stoichiometric loading capacity of the anthracycline drug doxorubicin (Dox). The on-demand drug release was realized by illuminating nanoconstructs with near-infrared (NIR) light. Furthermore, a higher degree of Dox release from the nanoconstructs was achieved in an acidic environment, compared to neutral conditions. The

Mobile low-cost analytical systems for the detection and quantitation of heavy metal contaminants such as lead (Pb 2+ ) and mercury (Hg 2+ ) in drinking water are critical in preventing the general population from exposure to the toxic metal ions. In this paper, we presented smartphone nano-colorimetry (SNC) as a new technique for multiplex-sensing of dissolved Pb 2+ and Hg 2+ . The sensing mechanism of SNC is based on the microscopic dark-field imaging of micro-or nanoscale sediments of yellow lead chromate (PbCrO4) and red mercury iodide (HgI2) on a glass-PDMS substrate, followed by intensity analysis to quantitatively measure the concentration of Pb 2+ and Hg 2+ in the water. We showed that SNC capable of detecting and quantitating Pb 2+ and Hg 2+ below the EPA action level for both metal ions at 15 ppb and 2 ppb, respectively. We envision that SNC will realize highly sensitive and rapid in-field quantitation of toxic heavy metal contaminants in drinking water, enable citizens to examine their water on-demand for better life-quality.

Lignocellulosic nanofibrils (LCNF) has caused great interest from researchers due to the benefits of high output, low operation cost, and weak environmental impact. The existence of lignin in LCNF ...