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.

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.

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.

Suppressing the photobleaching and photoluminescence intermittency of single near-infrared CdSeTe/ZnS quantum dots with p-phenylenediamine.

Intrinsic photobleaching and photoluminescence (PL) intermittency of single quantum dots (QDs), originating from photo-oxidation and photo-ionization respectively, are roadblocks for most single-dot applications. Here, we effectively suppress the photobleaching and the PL intermittency of single near-infrared emitting QDs with p-phenylenediamine (PPD). The PPD cannot only be used as a high-efficient reducing agent to remove reactive oxygen species around QDs to suppress the photo-oxidation, but can also bond with the surface defect sites of single QDs to reduce electron trap states to suppress the photo-ionization. It is shown that the survival time of single QDs, the on-state probability of PL intensity traces, and the total number of emitted photons are significantly increased for single QDs in PPD compared with that on glass coverslip.

Conjugated polymer nanoparticles: preparation, properties, functionalization and biological applications.

In the past few years, conjugated polymer nanoparticles (CPNs) have been successfully prepared and applied in the biological field because of their unique opto-electronic properties. The rapid development of CPNs is mainly attributed to their simple synthesis procedures and easy separation steps. The advantages of CPNs include high brightness, excellent photostability, low cytotoxicity, high quantum yield and versatile surface modification. The functionalization of CPNs with specific recognition elements imparts them good ability for targeted recognition and imaging in vitro and in vivo. CPNs can be applied to deliver drug and gene, and simultaneously to real-time monitor the release process due to their self-luminous characteristics. Moreover, CPNs can sensitize oxygen molecules to generate reactive oxygen species (ROS) which can kill adjacent bacteria and tumor cells. In this tutorial review, we provide a recent development of the preparation methods, properties, and functionalization strategies of CPNs, especially discussing their biological applications in targeted imaging, drug/gene delivery and biomedicine. The challenges and outlooks in this field will also be discussed.

Multi-colored fibers by self-assembly of DNA, histone proteins, and cationic conjugated polymers.

The development of biomolecular fiber materials with imaging ability has become more and more useful for biological applications. In this work, cationic conjugated polymers (CCPs) were used to construct inherent fluorescent microfibers with natural biological macromolecules (DNA and histone proteins) through the interfacial polyelectrolyte complexation (IPC) procedure. Isothermal titration microcalorimetry results show that the driving forces for fiber formation are electrostatic and hydrophobic interactions, as well as the release of counterions and bound water molecules. Color-encoded IPC fibers were also obtained based on the co-assembly of DNA, histone proteins, and blue-, green-, or red- (RGB-) emissive CCPs by tuning the fluorescence resonance energy-transfer among the CCPs at a single excitation wavelength. The fibers could encapsulate GFP-coded Escherichia coli BL21, and the expression of GFP proteins was successfully regulated by the external environment of the fibers. These multi-colored fibers show a great potential in biomedical applications, such as biosensor, delivery, and release of biological molecules and tissue engineering.

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.

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.

Preparation and optical property of new fluorescent nanoparticles.

A new fluorescent nanoparticle (PIOT-HA) is synthesized with cationic polyester (PIOT) and anionic hyaluronic acid (HA) by electrostatic interactions in an aqueous solution. The nanoparticles (NPs) are degradable upon treatments with alkali or hyaluronidase, which exhibits better biological safety and potential application in vitro and in vivo. Through specific interactions between the HA locating on the surfaces of PIOT-HA NPs and the CD44 protein over-expressed on the MDA-MB-231 cancer cell line, PIOT-HA NPs could selectively image the cancer cells. Upon white light irradiation, the PIOT-HA NPs can sensitize oxygen to generate reactive oxygen species (ROS) that inactivate the neighboring CD44 protein, which inhibits the migration of MDA-MB-231 cancer cells.

Multiplex detection of DNA mutations by the fluorescence fingerprint spectrum technique.

A fingerprint spectrum technique that utilizes cationic conjugated-polymer-based fluorescence resonance energy transfer (FRET) is used for multiplex detection of DNA mutations. This method detects as low as 5 % mutation of the total DNA. Ten PIK3CA mutations originating from 30 clinical breast cancer samples could be detected.

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.

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.

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.

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.

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.

Recognition of d-fructose based on tetra-boronic functionalized viologen in aqueous solution.

A highly selective and sensitive switch for d-fructose is formed by 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) fluorescent dye and the tetra-boronic acid viologen receptor ToBV. The sensing system can not only recognize d-fructose among seven natural d-monosaccharides but also may distinguish the enantiomer of d/l-fructose. The research rationale and results will offer a new strategy for the development of saccharides recognition.

A highly sensitive water-soluble system to sense glucose in aqueous solution.

A glucose sensing switch is formed by water soluble conjugated polymer (PP-S-BINOL) and boronic acid-functionalized benzyl viologen (o-BBV). The two-component system shows a high sensitivity for glucose sensing with a 17-fold increase in the fluorescence intensity in the presence of 100 mM glucose.

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.

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.