A Stable Open-Shell Conjugated Diradical Polymer with Ultra-High Photothermal Conversion Efficiency for NIR-Ⅱ Photo-Immunotherapy of Metastatic Tumor

Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.

Electrochemical detection of methyl-paraoxon based on bifunctional cerium oxide nanozyme with catalytic activity and signal amplification effect

A new electrochemical sensor for organophosphate pesticide(methyl-paraoxon)detection based on bifunctional cerium oxide(CeO_(2))nanozyme is here reported for the first time.Methyl-paraoxon was degraded into p-nitrophenol by using CeO_(2) with phosphatase mimicking activity.The CeO_(2) nanozymemodified electrode was then synthesized to detect p-nitrophenol.Cyclic voltammetry was applied to investigate the electrochemical behavior of the modified electrode,which indicates that the signal enhancement effect may attribute to the coating of CeO_(2) nanozyme.The current research also studied and discussed the main parameters affecting the analytical signal,including accumulation potential,accumulation time,and pH.Under the optimum conditions,the present method provided a wider linear range from 0.1 to 100 mmol/L for methyl-paraoxon with a detection limit of 0.06 mmol/L.To validate the proof of concept,the electrochemical sensor was then successfully applied for the determination of methyl-paraoxon in three herb samples,i.e.,Coix lacryma-jobi,Adenophora stricta and Semen nelumbinis.Our findings may provide new insights into the application of bifunctional nanozyme in electrochemical detection of organophosphorus pesticide.

De novo design of highly efficient type-Ⅰphotosensitizer based onπ-conjugated oligomer for photodynamic eradication of multidrug-resistant bacterial infections

Traditional photosensitizers show limited singlet oxygen generation in hypoxic infection lesions,which greatly suppress their performance in antibacterial therapy.Meanwhile,there still is lack of feasible design strategy for developing hypoxia-overcoming photosensitizers agents.Herein,radical generation ofπ-conjugated small molecules is efficiently manipulated by an individual selenium(Se)substituent.With this strategy,the first proof-of-concept study of a Se-anchored oligo(thienyl ethynylene)(OT-Se)with high-performance superoxide radical(O_(2)^(·-))and hydroxyl radical(·OH)generation capability is present,and achieves efficient antibacterial activities towards the clinically extracted multidrug-resistant bacteria methicillin-resistant S.aureus(MRSA)and carbapenem-resistant E.coli(CREC)at sub-micromolar concentration under a low white light irradiation(30 mW/cm^(2)).The water-dispersible OT-Se shows a good bacteria-anchoring capability,biocompatibility,and complete elimination of multidrug-resistant bacteria wound infection in vivo.This work offers a strategy to boost type-I photodynamic therapy(PDT)performance for efficient antibacterial treatments,advancing the development of antibacterial agents.

Targeting β-secretase with RNAi in neural stem cells for Alzheimer's disease therapy

There are several major pathological changes in Alzheimer＇s disease, including apoptosis of cho- linergic neurons, overactivity or overexpression of 13-site amyloid precursor protein cleaving enzyme 1 （BACE1） and inflammation. In this study, we synthesized a 19-nt oligonucleotide targeting BACE1, the key enzyme in amyloid beta protein （AI3） production, and introduced it into the pSilenCircle vector to construct a short hairpin （shRNA） expression plasmid against the BACE1 gene. We transfected this vector into C17.2 neural stem cells and primary neural stem cells, resulting in downregulation of the BACE1 gene, which in turn induced a considerable reduction in reducing AI3 protein production. We anticipate that this technique combining cell transplantation and gene ther- apy will open up novel therapeutic avenues for Alzheimer＇s disease, particularly because it can be used to simultaneously target several pathogenetic changes in the disease.

Near-infrared fluorescent aptamer-templated silver nanoclusters facilely synthesized for cellular imaging applications

Fluorescent metal nanoclusters(NCs)have received extensive attention for their potential uses in bionanotechnology.Here,we develop a facile strategy to synthesize near-infrared fluorescent silver nanoclusters(Ag NCs)stabilized by MUC1 aptamer.The MUC1-Ag NCs are characterized by UV–Vis absorption spectroscopy,fluorescence spectroscopy,transmission electron microscopy,and fluorescence lifetime.These results indicated that the MUC1-Ag NCs possess bright near-infrared luminescence,high stability,and excellent biocompatibility.The cellular imaging of MUC1-Ag NCs by confocal laser microscopy demonstrated them to be promising candidates as novel fluorescent probes for biomedical application.

Design of antibacterial peptide-like conjugated molecule with broad spectrum antimicrobial ability

Increasing multidrug-resistant （MDR） superbugs emerge worldwide causing a public health crisis. Consequently, it is urgent to find new antibiotics with efficient broad-spectrum antimicrobial activity. By virtue of versatility in molecular design, a new peptide-like cell membrane-broken molecule, oligo-（7,7＇-bifluoren-benzo[c][1,2,5]thiadiazole） （OFBT） possessing a conjugated backbone and eight pendant guanidyl moieties was designed and synthesized. OFBT exhibits favorable broad-spectrum of antirnicrobial activity to pathogens including Gram-negative and Gram-positive bacteria, and fungi with the minimum inhibitory concentration （MIC） below 3.0 μM. Moreover, OFBT exhibits high selectivity for pathogens over human cells to make it a promising broad spectrum antimicrobial agent.

Regulation of excitation transit ons by molecular design endowing full-color-tunable emissions with unexpected high quantum yields for bioimaging application

Organic fluorophores are indispensible in chemical/biological imaging. The conjugated fluorescent molecules simultaneously possessing highly tunable emission, high quantum yield in solvents of different polarities, and large Stokes shift are quite rare. Herein, we report a new category of fluorophores based on diarylated thieno[3,4-b]thiophenes efficiently synthesized by direct C-H arylation reaction. TbT-Fluors showed full-color-tunable emissions with large Stokes shifts. Intriguingly,the fluorescence quantum yields of TbT-Fluors are barely sensitive to solvent polarities, approaching 100%. Based on photophysical and theoretical investigations, we found that the enhanced oscillator strength of the S_1-S_0 transition and increased T2-S1 energy difference can sufficiently compensate the negative effect from the decreased energy gap and increased reorganization energy in dimethyl sulfoxide(DMSO). Bioimaging applications revealed that some TbT-Fluors can penetrate the cell membrane and are superior for imaging in terms of high photochemical stability and low cytotoxicity. Furthermore, TbT-PhF exhibits specific colocalization with mitochondria in living cells.

Perfecting and extending the near-infrared imaging window

In vivo fluorescence imaging in the second near-infrared window(NIR-II)has been considered as a promising technique for visualizing mammals.However,the definition of the NIR-II region and the mechanism accounting for the excellent performance still need to be perfected.Herein,we simulate the photon propagation in the NIR region(to 2340 nm),confirm the positive contribution of moderate light absorption by water in intravital imaging and perfect the NIR-II window as 900–1880 nm,where 1400–1500 and 1700–1880 nm are defined as NIR-IIx and NIR-IIc regions,respectively.Moreover,2080–2340 nm is newly proposed as the third near-infrared(NIR-III)window,which is believed to provide the best imaging quality.The wide-field fluorescence microscopy in the brain is performed around the NIRIIx region,with excellent optical sectioning strength and the largest imaging depth of intravital NIR-II fluorescence microscopy to date.We also propose 1400 nm long-pass detection in off-peak NIR-II imaging whose performance exceeds that of NIR-IIb imaging,using bright fluorophores with short emission wavelength.

Confocal visible/NIR photoacoustic microscopy of tumors with structural, functional, and nanoprobe contrasts

Distinguishing early-stage tumors from normal tissues is of great importance in cancer diagnosis.We report fiberbased confocal visible/near-infrared(NIR)optical-resolution photoacoustic microscopy that can image tumor microvasculature,oxygen saturation,and nanoprobes in a single scanning.We develop a cost-efficient single laser source that provides 532,558,and 1064 nm pulsed light with sub-microseconds wavelength switching time.Via dual-fiber illumination,we can focus the three beams to the same point.The optical and acoustic foci are confocally aligned to optimize the sensitivity.The visible and NIR wavelengths enable simultaneous tumor imaging with three different contrast modes.Results show obvious angiogenesis,significantly elevated oxygen saturation,and accumulated nanoparticles in the tumor regions,which offer comprehensive information to detect the tumor.This approach also allows us to identify feeding and draining vessels of the tumor and thus to determine local oxygen extraction fraction.In the tumor region,the oxygen extraction fraction significantly decreases along with tumor growth,which can also assist in tumor detection and staging.Fiber-based confocal visible/NIR photoacoustic microscopy offers a new tool for early detection of cancer.