Organic-Inorganic Interfacial Dipole Induced by Energy Level Alignment for Efficient Photocatalytic Sterilization.

Photocatalytic molecules are considered to be one of the most promising substitutions of antibiotics against multidrug-resistant bacterial infections. However, the strong excitonic effect greatly restricts their efficiency in antibacterial performance. Inspired by the interfacial dipole effect, a Ti3C2 MXene modified photocatalytic molecule (MTTTPyB) is designed and synthesized to enhance the yield of photogenerated carriers under light irradiation. The alignment of the energy level between Ti3C2 and MTTTPyB results in the formation of an interfacial dipole, which can provide an impetus for the separation of carriers. Under the role of a dipole electric field, these photogenerated electrons can rapidly migrate to the side of Ti3C2 for improving the separation efficiency of photogenerated electrons and holes. Thus, more electrons can be utilized to produce reactive oxygen species (ROS) under light irradiation. As a result, over 97.04% killing efficiency can be reached for Staphylococcus aureus (S. aureus) when the concentration of MTTTPyB/Ti3C2 was 50 ppm under 660 nm irradiation for 15 min. A microneedle (MN) patch made from MTTTPyB/Ti3C2 was used to treat the subcutaneous bacterial infection. This design of an organic-inorganic interface provides an effective method to minimize the excitonic effect of molecules, further expanding the platform of inorganic/organic hybrid materials for efficient phototherapy.

Induced Ferroptosis Pathway by Regulating Cellular Lipid Peroxidation With Peroxynitrite Generator for Reversing "Cold" Tumors.

Overcoming the resistance of tumor cells to apoptosis and immunosuppression is an important challenge to improve tumor immunotherapy. Non-apoptotic death mode of ferroptosis has been regarded as a new strategy to enhance tumor immunotherapy against drug-resistant cancers. The lethal accumulation of lipid peroxides (LPO) determines the progress of ferroptosis. The high susceptibleness of ferroptosis provides an opportunity for combating triple-negative breast cancer. Reactive nitrogen species (RNS) produced by nitric oxide (NO) and reactive oxygen species (ROS) is more lethal than ROS for tumor cells. Herein, an RNS-mediated immunotherapy strategy for inducing ferroptosis pathway is proposed by improving LPO accumulation, and constructed a multifunctional liposome (Lipo-MT-SNAP) comprised of peroxynitrite (ONOO-) generator, tumor targeted group, inhibiting glutathione peroxidase 4 (GPX4), and basic units (dipalmitoyl phosphatidylcholine and cholesterol). The significant enhancement of LPO resulted from the intense oxidative damage of ONOO- impaired synthesis of GPX4 by depleting glutathione, which further amplified ferroptosis and triggered immunogenic cell death. In vivo, RNS-mediated photoimmunotherapy can promote polarization of M2 to M1 macrophages and dendritic cells maturation, further infiltrate T cells, regulate the secretion of inflammatory factors, and reprogram the tumor microenvironment. The powerful RNS-mediated ferroptosis induces strong immunogenicity and effectively inhibit tumor proliferation.

Customized A-D-A type molecule to construct a nitric oxide nanogenerator with enhanced antibacterial activity for infected wound healing.

Bacterial infections pose an increasingly serious threat to global health due to the development of drug-resistant strains. Developing a method to efficiently kill bacteria and promote tissue repair is imperative to decrease the damage from bacterial infection, especially infected wounds. Herein, a biofriendly and light-controlled nitric oxide (NO) generator HFB with simultaneous bacterial killing and wound repair properties is reported based on a tailored light-responsive molecule F(EIBC)2. HFB demonstrates an appropriate photothermal conversion efficiency of 33.4% and type I reactive oxygen species (˙OH and H2O2) generation capability to simultaneously trigger NO generation and potently kill bacteria. Furthermore, HFB can effectively eradicate mature bacterial biofilms with the aid of favorable permeability of NO. Additionally, HFB effectively eradicates Staphylococcus aureus in infected wounds of living mice and accelerates healing via NO-induced angiogenesis and collagen deposition. Owing to the encapsulated human serum albumin (HSA), heavy metal-free feature, and synergistic killing mechanism, HFB exhibits good biosafety to surrounding tissue and major organs. This work provides a novel dual-functional photo-responsive molecule and a potential light-controlled release platform for the treatment of bacterial infections.

Chiral Co-Assembly with Narrowband Multi-Resonance Characteristics for High-Performance Circularly Polarized Organic Light-Emitting Diodes.

A promising kind of ternary chiral co-assemblies with high PLQY, large dissymmetry factor (glum), and narrowband multi-resonance characteristics are achieved by codoped-thermal annealing treatments of achiral luminescent polymer F8BT, chiral inducers R/S-5011, and achiral FRET acceptor DBN-ICZ. The optimized co-assemblies (F8BT)0.9-(R/S-5011)0.1-(DBN-ICZ)0.005 display narrowband yellow emission with full-width half maximum (FWHM) of 37 nm, PLQY of 79%, and intense CPL signals with |glum| of up to 0.26. Meaningfully, solution-processed CP-OLEDs by using those ternary chiral co-assemblies as emitting layer are successfully fabricated, which display yellow circularly polarized electroluminescence (CPEL) with EQEmax of 4.6% and gEL of up to 0.16. The corresponding Q-factor could reach up to 7.36 × 10-3, which is the highest of all the reported CP-OLEDs. Moreover, the devices also exhibit excellent comprehensive device performance with low Von of 7.0 V, high Lmax of about 25 000 cd m-2, extremely low efficiency roll-off with EQE of 4.3% at 10 000 cd m-2, as well as narrowband EL with FWHM of only 39 nm. The proposed ternary co-assembly strategy in fabricating CP-OLED provides the possibility to achieve high comprehensive device performance such as balancing high EQE and large gEL value, as well as narrowband emission, high brightness and low efficiency roll-off simultaneously.

Tuning molecular assembly behavior to amplify the sonodynamic activity of porphyrins for efficient antibacterial therapy.

Sonodynamic therapy (SDT) is a promising strategy to treat deep-seated bacterial infections with good tissue penetration and spatiotemporal controllability. However, the low ROS generation efficiency of current sonosensitizers limits the development of SDT. Herein, we report a porphyrin derivative, TAPyPP-2, the sonodynamic activity of which is enhanced with less oxygen dependence by tuning its molecular assembly behavior. TAPyPP-2 can spontaneously form an ultra-small nano-assembly with a diameter of 6 nm in water by conjugation with primary amine salt-decorated pyridinium via π-π staking. The ultra-small assembly behavior can lower the energy gap between singlet and triplet states to 0.01 eV and promote the separation of holes and electrons, which facilitates ROS generation under ultrasound irradiation, in particular type I ROS. The unique hydrophilic ratio and positive charges endow TAPyPP-2 with superior abilities to interact with Staphylococcus aureus, resulting in extremely high sonodynamic antibacterial activity. Therefore, TAPyPP-2 successfully kills Staphylococcus aureus bacteria in the enclosed cavity of synovial joint and achieves effective SDT of septic arthritis. This work is anticipated to motivate enormous interest in the development of efficient SDT.

Tailored Phototherapy Agent by Infection Site In Situ Activated Against Methicillin-Resistant S. aureus.

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a promising treatment approach for multidrug resistant infections. PDT/PTT combination therapy can more efficiently eliminate pathogens without drug resistance. The key to improve the efficacy of photochemotherapy is the utilization efficiency of non-radiation energy of phototherapy agents. Herein, a facile phototherapy molecule (SCy-Le) with the enhancement of non-radiative energy transfer is designed by an acid stimulation under a single laser. Introduction of the protonated receptor into SCy-Le results in a distorted intramolecular charge in the infected acidic microenvironment, pH ≈ 5.5, which in turn, enhances light capture, reduces the singlet-triplet transition energies (ΔES1-T1), promotes electron system crossing, enhances capacity of reactive oxygen species generation, and causes a significant increase in temperature by improving vibrational relaxation. SCy-Le shows more than 99% bacterial killing rate against both methicillin-resistant Staphylococcus aureus and its biofilms in vitro and causes bacteria-induced wound healing in mice. This work will provide a new perspective for the design of phototherapy agents, and the emerging photochemotherapy will be a promising approach to combat the problem of antibiotic resistance.

Symmetrical Localized Built-in Electric Field by Induced Polarization Effect in Ionic Covalent Organic Frameworks for Selective Imaging and Killing Bacteria.

Photocatalytic materials are some of the most promising substitutes for antibiotics. However, the antibacterial efficiency is still inhibited by the rapid recombination of the photogenerated carriers. Herein, we design a cationic covalent organic framework (COF), which has a symmetrical localized built-in electric field due to the induced polarization effect caused by the electron-transfer reaction between the Zn-porphyrin unit and the guanidinium unit. Density functional theory calculations indicate that there is a symmetrical electrophilic/nucleophilic region in the COF structure, which results from increased electron density around the Zn-porphyrin unit. The formed local electric field can further inhibit the recombination of photogenerated carriers by driving rapid electron transfer from Zn-porphyrin to guanidinium under light irradiation, which greatly increases the yield of reactive oxygen species. This COF wrapped by DSPE-PEG2000 can selectively target the lipoteichoic acid of Gram-positive bacteria by electrostatic interaction, which can be used for selective discrimination and imaging of bacteria. Furthermore, this nanoparticle can rapidly kill Gram-positive bacteria including 99.75% of Staphylococcus aureus and 99.77% of Enterococcus faecalis at an abnormally low concentration (2.00 ppm) under light irradiation for 20 min. This work will provide insight into designing photoresponsive COFs through engineering charge behavior.

Bioactive AIEgens Tailored for Specific and Sensitive Theranostics of Gram-Positive Bacterial Infection.

Diseases caused by bacterial infections are increasingly threatening human health. As a major part of the microbial family, Gram-positive bacteria induce severe infections in hospitals and communities. Therefore, developing antibacterial materials that can recognize bacteria and specifically kill them is significant to cope with fatal bacterial infection. To this end, we designed and prepared a series of positively charged photosensitizers with an aggregation-induced emission feature and a type I reactive oxygen species (ROS) generation ability. Based on a molecular engineering strategy, the PS abbreviated to MTTTPy that owns a superior ROS generation ability and red emission in aggregation is obtained by adjusting bridging groups. Due to the unique molecular structure, MTTTPy can sensitively and specifically recognize and light up Gram-positive bacteria through electrostatic adsorption and void permeability. In addition, it can kill 95% of the recognized bacteria at a low concentration of 0.5 µM by generating oxygen-independent ROS under white light irradiation. Both in vitro and in vivo studies verify the sensitive and specific recognition and killing effect of MTTTPy toward Gram-positive bacteria. This work provides superior material-integrated diagnosis and treatment for Gram-positive bacteria-caused infectious diseases and shows potential for addressing bacterial resistance.

Injectable thermosensitive hydrogel to enhance the photothermal ablation and systemic immunotherapy of breast tumors.

As the high-frequency tumor in women around the world, breast cancer has high mortality due to metastasis tumors making it difficult to cure. Herein, we report a near-infrared (NIR) activated bio-multifunctional thermosensitive hydrogel (denoted as AMDR) with powerful cell killing and immunogenicity amplifying ability. Based on the molecular engineering strategy, a photothermal agent (M-4) with 52.4% conversion efficiency was synthesized. Accordingly, the designed injectable thermosensitive hydrogel AMDR is simply fabricated by the employment of the M-4 photothermal agent, doxorubicin hydrochloride (DOX) as the antitumor drug, and imiquimod (R837) as the immunologic adjuvant by self-assembly. Under NIR irradiation, the AMDR hydrogel can generate local mild heat to release DOX for synergistic killing of tumor cells with little damage to normal cells. The immunogenic cell death induced by potent in situ killing combined with heat-released R837 can trigger robust immune response to inhibit and kill metastasis tumors. The developed AMDR hydrogel is successfully applied in the treatment of primary tumors and inhibition of distal tumors of tumor-bearing mice. The study provides a novel strategy and platform for complete treatment of breast cancer and also offers ideas for designing high-efficiency photothermal agents.

Self-assemblies with cascade effect to boost antitumor systemic immunotherapy.

Bio-organic hybrid self-assemblies based on amino acids, conjugated polymers, Fe3+ and enzymes are fabricated with tumor environment-responsive and light-triggered NO release properties. By sequential energy consumption, NO attack and immune activation, FFPG shows boosted antitumor activity toward both primary and distant tumors. The three-level cascade strategy (starvation/NO/immunotherapy) adopted in this work offers a pathway to address the dilemma of low cure rate of malignant tumors.

A tailored and red-emissive type I photosensitizer to potentiate photodynamic immunotherapy.

Photodynamic immunotherapy (PDIT) has emerged as a technique which shows great potential in eradicating malignant tumors due to its advantages of simultaneously damaging primary tumors and inhibiting tumor metastasis and recurrence. However, the hypoxic microenvironment of tumor tissue and immune escape are two major challenges that PDIT faces. Hence, a well-designed water-soluble type I photosensitizer (TbT-TPP) based on a "D-A" strategy is reported for imaging-guided PDIT. The enhanced dihedral angle, prolonged conjugation length, strong electron withdrawing effect, and electron-rich condition endow TbT-TPP with a superior type I ROS generation ability and aggregation-induced red emission, which is demonstrated by comparision with the control molecule. We demonstrate that in hypoxic tissue, TbT-TPP can light up tumors and further efficiently kill them, triggering immunogenic cell death by generating type I ROS, which sequentially promotes the maturation of dendritic cells and enhances the T-cell response to tumor cells. Combined with immune adjuvant R837, TbT-TPP based-PDIT achieves the complete elimination of solid tumors and inhibition of tumor metastasis of living mice. This work provides a potential theranostic material and new insights into the improvement of PDIT against hypoxic tumors.

Multifunctional Self-Assembly with NIR Light-Activated Cascade Effect for Improving Local Treatment on Solid Tumors.

Incomplete local treatment of solid tumors is the main cause of tumor difficult to cure, and easily leads to tumor metastasis and recurrence. The dense external matrix and hypoxic microenvironment of solid tumors severely restrict the therapy efficacy of local tumors. Enhancing the infiltration ability of agents to tumor tissues and adapting the therapy mode favored to hypoxic microenvironments are beneficial to improve the cure rate of tumors. In this work, we designed and developed a self-assembled biomaterial with a cascade effect triggered by near-infrared light. The self-assembly was combined of biotin, phase change material (PNIPAM), photochemical agent (ATT-2), and alkyl radical generator (AIPH). In the assembly, biotin acted as a targeted group. ATT-2 was used to provide heat to synergistically induce the phase change and decompose alkyl radicals. The superficial and deep tumors were ablated by heat and alkyl radicals with white light irradiation of the assembly, respectively. The assay in vivo showed that the self-assembly could effectively eliminate local lesions of solid tumors. This work provides new insights for improving the cure rate of tumors, which not only develops biomaterials adapted to the tumor microenvironment, but also proposes new therapies for complete elimination of solid tumors.

High-Efficiency Circularly Polarized Electroluminescence from TADF-Sensitized Fluorescent Enantiomers.

A couple of fluorescent enantiomers, which are suitable for the emitters of high-efficiency TADF-sensitized CP-OLEDs, have been developed. The enantiomers show configurational stability, high PLQY of 98 %, large kr of 7.8×107  s-1 , and intense CPL activities with |glum | values of about 2.5×10-3 . Notably, by using matchable TADF sensitizer, the enantiomers were then exploited as emitter to fabricate CP-OLEDs. The TADF-sensitized CP-OLEDs not only show mirror-image CPEL activities with gEL values of +1.8×10-3 and -1.4×10-3 , but also display fast start-up featuring with low VT of 3.0 V as well as driving voltage of 4.8 V at 10 000 cd m-2 . Meaningfully, the TADF-sensitized fluorescent devices show high EQEmax of 21.5 % and extremely low efficiency roll-off, whose EQEs are 21.2 % and 15.3 % at 1000 and 10 000 cd m-2 , respectively. The obtained EQEs are comparable to those of CP-TADF emitters, which provides a promising perspective to break through the EL efficiency limit of CP-FL emitters.

Ratiometric sensing of Zn2+ with a new benzothiazole-based fluorescent sensor and living cell imaging.

A new fluorescent probe, 3-(benzo[d]thiazol-2-yl)-5-bromosalicylaldehyde-4N-phenyl thiosemicarbazone (BTT), for ratiometric sensing of Zn2+ ions in methanol/HEPES buffer solution (3 : 2, pH = 7.4) is reported in this paper. The presence of Zn2+ ions yields a significant blue shift in the maximum emission of BTT from 570 nm to 488 nm, accompanied by a clear color change from orange to green. This emission change of BTT upon binding to Zn2+ in a 1 : 1 ratio may be due to the block of excited state intramolecular proton transfer (ESIPT) as well as chelation enhanced fluorescence (CHEF) on complex formation. The limit of detection (LOD) determined for Zn2+ quantitation was down to 37.7 nM. In addition, the probe BTT displays the ability to image both exogenous Zn2+ ions loaded into HeLa cells and endogenous Zn2+ distribution in living SH-SY5Y neuroblastoma cells.

Organic Solar Cells with 18% Efficiency Enabled by an Alloy Acceptor: A Two-in-One Strategy.

The trade-off between the open-circuit voltage (Voc ) and short-circuit current density (Jsc ) has become the core of current organic photovoltaic research, and realizing the minimum energy offsets that can guarantee effective charge generation is strongly desired for high-performance systems. Herein, a high-performance ternary solar cell with a power conversion efficiency of over 18% using a large-bandgap polymer donor, PM6, and a small-bandgap alloy acceptor containing two structurally similar nonfullerene acceptors (Y6 and AQx-3) is reported. This system can take full advantage of solar irradiation and forms a favorable morphology. By varying the ratio of the two acceptors, delicate regulation of the energy levels of the alloy acceptor is achieved, thereby affecting the charge dynamics in the devices. The optimal ternary device exhibits more efficient hole transfer and exciton separation than the PM6:AQx-3-based system and reduced energy loss compared with the PM6:Y6-based system, contributing to better performance. Such a "two-in-one" alloy strategy, which synergizes two highly compatible acceptors, provides a promising path for boosting the photovoltaic performance of devices.

Facile antibacterial materials with turbine-like structure for P. aeruginosa infected scald wound healing.

Pseudomonas aeruginosa (P. aeruginosa) is a popular hospital pathogen and the major cause of morbidity and mortality in patients with cystic fibrosis (CF) and impaired immune system. Herein, we designed and synthesized a series of organic molecules MTEBT-n (n = 1, 2, 3) to specifically and effectively kill P. aeruginosa. Hydrophobic triphenylamine was selected as the skeleton, and hydrophilic primary ammonium salts that can easily penetrate the cell walls of Gram-negative bacteria and accumulate in the bacteria were used to adjust the hydrophilic-hydrophobic ratio of the molecules, resulting in different antibacterial activity. As the hydrophilic-hydrophobic ratio increased in the structures from MTEBT-1 to MTEBT-3, the antibacterial activity of the three molecules were gradually enhanced with killing effects of 25%, 75% and 95% against P. aeruginosa, respectively. The antibacterial mechanisms of MTEBT-n were demonstrated to destroy the bacterial membrane, which could effectively prevent the development of drug resistance. In addition, MTEBT-3 with the highest antibacterial activity could inhibit P. aeruginosa biofilm very well, and heal the P. aeruginosa infected scald wounds. This work provides a potential organic antimicrobial material for clinical antimicrobial therapy of P. aeruginosa infection, and offers a molecular engineering strategy for designing new antimicrobials.

Molecular engineering to boost the photothermal effect of conjugated oligomer nanoparticles.

Photothermal therapy has great potential in the treatment of diseases; however, the photothermal property is a key factor limiting the therapeutic effect of photothermal materials. Most strategies to improve the photothermal performance of photothermal materials focus on increasing their photothermal conversion efficiency (PCE) by promoting the non-radiative transition process. However, a strong ability to absorb light is also a significant factor to enhance the photothermal performance of materials because it determines the amount of acquired energy to transform to heat. Therefore, in this work, we utilized molecular engineering to introduce ethynyl into the molecular structure of conjugated molecules to significantly enhance their ability to absorb light and improve their photothermal performance. The M2-NPs made of the conjugated oligomer named M2 with ethynyl exhibited a two-fold greater mass extinction coefficient (30.26 L g-1 cm-1) than that of nanoparticles M1-NPs with a similar structure but no ethynyl (15.34 L g-1 cm-1). Furthermore, M2-NPs could kill 97% of bacteria at a concentration of 7.0 µg mL-1, which is less than that of M1-NPs (13.0 µg mL-1). In addition, M2-NPs could successfully treat the infected wounds in mice with good biosafety. This provides a new idea for effectively improving the photothermal performance of photothermal materials via molecular design and inspires the further development of novel superior photothermal agents.

Intelligent Hybrid Hydrogels for Rapid In Situ Detection and Photothermal Therapy of Bacterial Infection.

Diseases induced by bacterial infections increasingly threaten the health of people all over the world; thus, it is urgent and significant to early diagnose and effectively eliminate infections to save people's lives. To this end, we synthesized an intelligent hydrogel that integrated in situ visualized diagnosis and photothermal therapy of bacterial infections. By simply and subtly incorporating pH-sensitive bromothymol blue (BTB) and near-infrared (NIR)-absorbing conjugated polymer (termed as PTDBD) into thermosensitive chitosan (CS)-based hydrogel, the synthesized BTB/PTDBD/CS hydrogel can diagnose the acidic microenvironment of Staphylococcus aureus (S. aureus) biofilm and infected wounds by showing visualized color change. After rapid diagnosis, the hydrogel can immediately treat the infection site by local hyperthermia under irradiation of NIR laser (808 nm) and even the stubborn biofilm that is difficult to eradicate. Since the dominating antibacterial mechanism is hyperthermia, the hybrid hydrogel shows broad-spectrum antibacterial activity against Gram-positive, Gram-negative, and drug-resistant bacteria. In addition, it has low cytotoxicity to normal cells and no effect on the main organs of mice. It paves a brand new avenue to develop smart and facile diagnosis and a treatment platform for bacterial infections.

Design, Synthesis, Molecular Docking, and Biological Evaluation of New Emodin Anthraquinone Derivatives as Potential Antitumor Substances.

The emodin anthraquinone derivatives are generally used in traditional Chinese medicine due to their various pharmacological activities. In the present study, a series of emodin anthraquinone derivatives have been designed and synthesized, among which 1,3-dihydroxy-6,8-dimethoxyanthracene-9,10-dione is a natural compound that has been synthesized for the very first time, and 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione is a compound that has never been reported earlier. Interestingly, while total seven of these compounds showed neuraminidase inhibitory activity in influenza virus with inhibition rate more than 50 %, specific four compounds exhibited significant inhibition of tumor cell proliferation. The further results demonstrate that 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione showed the best anticancer activity among all the synthesized compounds by inducing highest apoptosis rate to HCT116 cancer cells and arresting their G0/G1 cell cycle phase, through elevation of intracellular level of reactive oxygen species (ROS). Moreover, the binding of 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione with BSA protein has thoroughly been investigated. Altogether, this study suggests the neuraminidase inhibitory activity and antitumor potential of the new emodin anthraquinone derivatives.

Novel Anthraquinone Compounds Inhibit Colon Cancer Cell Proliferation via the Reactive Oxygen Species/JNK Pathway.

A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine (8a) showed the greatest inhibition of HCT116 cell activity with an IC50 of 17.80 µg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment.