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Pathogenic bacteria infections bring about a substantial risk to human health. Given the development of antibiotic-resistance bacteria, alternative antibacterial strategies with great inactivation efficiency and bacteria-binding ability are extremely attractive. In this work, a metabolic labeling photosensitizer, prepared by the coupling of commercial IR820 and d-propargylglycine (a type of d-amino acid, DAA) via a straightforward one-step incubation (IR820-DAA), could metabolically be incorporated into the bacterial wall via enzymatic reactions, thus enhancing antibacterial efficiency. The laser energy at 808 nm could make IR820-DAA a synergistic photothermal/photodynamic agent for efficient antibacterial therapy and wound healing. Furthermore, IR820-DAA exhibits good water solubility and biological safety for clinical translation and even possesses biofilm degradation activity toward methicillin-resistant

ConspectusFluorescence bioimaging in the second near-infrared window (NIR-II, 1000–1700 nm) is a superior visualization tool with deeper penetration and higher spatial resolution than the tradition...

Metallic aerogels (MAs), imparting the active catalytic properties of nanostructured noble metals to macroscopic aerogels, draw tremendous interest in diverse fields owing to the unique features of three-dimensional interconnected channels, self-supported architectures, and pure metallic backbones. Moreover, flexible manipulation of compositions, high electrical conductivity, and abundant active sites of MAs contribute to the great potential to mimic natural enzymes. However, the cumbersome synthetic process takes a couple of hours to days, and unavoidable impurities usually impede surface electrons/mass transfer, posing the decrease of stability and enzyme-like activity of MAs. Here, a PdIr bimetallic aerogel prepared in the ethanol phase via spontaneous assembly and a surfactant-free strategy is reported. Gelation kinetics of PdIr aerogels in ethanol is increased with 2-4 orders of magnitude compared to the traditional preparation method in water. Owing to the intrinsic physicochemical properties, PdIr aerogels exhibit the high activity of peroxidase mimics using 3,3',5,5'-tetramethylbenzidine as a chromogenic probe. In addition, the PdIr aerogels maintain relatively high activity at an elevated temperature and pH of 3-7, demonstrating their good stability and survivability. Utilizing the exceptional peroxidase-like activity of PdIr aerogels, we realized the quantitative bioassay for H

This article explored the application of novel organic-inorganic hybrid polystyrene nanoparticles (PSNPs) with trichromatic luminescence for the detection of latent fingerprints. The PSNPs were synthesized by encapsulated Eu(DBM)3phen, coumarin 6, and FDBT into the polystyrene nanoparticles through the swelling method and applied them to visualize latent fingerprints. The PSNPs had a spherical morphology with an average diameter of 310.7 nm, and they emitted trichromatic fluorescence (525 nm/570 nm/610 nm) under 365 nm excitation wavelength with green/yellow/red color under filters. They were less likely to aggregate, float or stain the background when treating fingerprints. The developed fingerprints with excellent clarity of ridges and contrast could be viewed, and the digital magnification of fluorescence-developed fingerprints provided more minutiae details about some regional patterns. The colorimetric and fluorescent trichromatic light could provide complementary signals without the background interference from fluorescent substrates and/or complex multicolor surfaces, which improved the applicability of fluorescent nanoparticles for fingerprints development. PSNPs are promising for the detection of latent fingerprints and practical criminal investigations with their ease of operation, eco-friendly properties, and excellent trichromatic optical performance.

Photoacoustic imaging-guided photothermal therapy in the second near-infrared (NIR-II) window shows promise for clinical deep-penetrating tumor phototheranostics. However, ideal photothermal agents in the NIR-II window are still rare. Here, the emeraldine salt of polyaniline (PANI-ES), especially synthesized by a one-pot enzymatic reaction on sodium bis(2-ethylhexyl) sulfosuccinate (AOT) vesicle surface (PANI-ES@AOT, λmax ≈ 1000 nm), exhibits excellent dispersion in physiological environment and remarkable photothermal ability at pH 6.5 (photothermal conversion efficiency of 43.9%). As a consequence of the enhanced permeability and retention effect of tumors and the doping-induced photothermal effect of PANI-ES@AOT, this pH-sensitive NIR-II photothermal agent allows tumor acidity phototheranostics with minimized pseudosignal readout and subdued normal tissue damage. Moreover, the enhanced fluidity of vesicle membrane triggered by heating is beneficial for drug release and allows precise synergistic therapy for an improved therapeutic effect. This study highlights the potential of template-oriented (or interface-confined) enzymatic polymerization reactions for the construction of conjugated polymers with desired biomedical applications.

Fluorescence imaging of biological systems in the second near-infrared (NIR-II, 1000–1700 nm) window has shown promise of high spatial resolution, low background, and deep tissue penetration owing to low autofluorescence and suppressed scattering of long wavelength photons. Here we develop a bright organic nanofluorophore (named p-FE) for high-performance biological imaging in the NIR-II window. The bright NIR-II >1100 nm fluorescence emission from p-FE affords non-invasive in vivo tracking of blood flow in mouse brain vessels. Excitingly, p-FE enables one-photon based, three-dimensional (3D) confocal imaging of vasculatures in fixed mouse brain tissue with a layer-by-layer imaging depth up to ~1.3 mm and sub-10 µm high spatial resolution. We also perform in vivo two-color fluorescence imaging in the NIR-II window by utilizing p-FE as a vasculature imaging agent emitting between 1100 and 1300 nm and single-walled carbon nanotubes (CNTs) emitting above 1500 nm to highlight tumors in mice., Imaging in the second near-infrared window has attracted attention due to superior penetration depth and low signal interference. Here, the authors describe a new organic nano fluorophore with high quantum yield and demonstrate its use for in vivo imaging.

Organic fluorophores have been widely used for biological imaging in the visible and the first near-infrared windows. However, their application in the second near-infrared window (NIR-II, 1000-1700 nm) is still limited mainly due to low fluorescence quantum yields (QYs). Here, we explore molecular engineering on the donor unit to develop high performance NIR-II fluorophores. The fluorophores are constructed by a shielding unit-donor(s)-acceptor-donor(s)-shielding unit structure. Thiophene is introduced as the second donor connected to the shielding unit, which can increase the conjugation length and red-shift the fluorescence emission. Alkyl thiophene is employed as the first donor connected to the acceptor unit. The bulky and hydrophobic alkyl thiophene donor affords larger distortion of the conjugated backbone and fewer interactions with water molecules compared to other donor units studied before. The molecular fluorophore IR-FTAP with octyl thiophene as the first donor and thiophene as the second donor exhibits fluorescence emission peaked at 1048 nm with a QY of 5.3% in aqueous solutions, one of the highest for molecular NIR-II fluorophore reported so far. Superior temporal and spatial resolutions have been demonstrated with IR-FTAP fluorophore for NIR-II imaging of the blood vessels of a mouse hindlimb.

Redox-responsive linkages dispersed in the backbones of the synthetic polymers, while young in the current spectrum of the biomedical application, are rapidly extending into their niche. In the present work, triblock copolymer PEG-PLA-PEG synthesized and characterized by 1H -NMR and SEC can self-assemble into redox-responsive micelles in aqueous media with nanosized 33nm and 47nm. And the copolymers PEG2000-PLA3000-PEG2000 and PEG2000-PLA5000-PEG2000 present lower CMC with 0.034 and 0.022mg/mL, and higher DLC of 4.28% and 5.14% respectively, compared with that of diblock copolymer. Moreover, drug release from the micelles can be triggered and significantly accelerated in reductive environment. The low cytotoxicity of redox-responsive micelles was confirmed by MTT assay against NIH 3T3 cells. All of these results demonstrated that these polymeric micelles self-assembled from double-disulfide tethered block copolymers are promising carriers for the redox-responsive intracellular delivery of hydrophobic anticancer drugs.

Deepening our understanding of mammalian gut microbiota has been greatly hampered by the lack of a facile, real-time, and in vivo bacterial imaging method. To address this unmet need in microbial visualization, we herein report the development of a second near-infrared (NIR-II)-based method for in vivo imaging of gut bacteria. Using d-propargylglycine in gavage and then click reaction with an azide-containing NIR-II dye, gut microbiota of a donor mouse was strongly labeled with NIR-II fluorescence on their peptidoglycan. The bacteria could be readily visualized in recipient mouse gut with high spatial resolution and deep tissue penetration under NIR irradiation. The NIR-II-based metabolic labeling strategy reported herein, provides, to the best of our knowledge, the first protocol for facile in vivo visualization of gut microbiota within deep tissues, and offers an instrumental tool for deciphering the complex biology of these gut "dark matters".

Redox-responsive micelles self-assembled from triblock copolymers of poly( l -lactic acid)-poly(ethylene glycol)-poly( l -lactic acid) ( PLA-PEG-PLA) with double-disulfide linkage in the backbone were synthesized and characterized by proton nuclear magnetic resonance ( 1 H NMR) and size exclusion chromatography (SEC), in which both PEG ( M n = 1000, 2000 and 4000 g mol −1 ) and PLA ( M n = 1600 g mol −1 ) have different molecular weights respectively. The triblock copolymers PLA 3000 -PEG 2000 -PLA 3000 and PLA 3000 -PEG 4000 -PLA 3000 can self-assemble into flower-like micelles in aqueous media with average diameters 110 nm and 43 nm and lower critical micelle concentrations (CMC) 0.017 and 0.014 mg mL −1 respectively compared with that of diblock copolymers. Moreover, in vitro drug release analyses indicated that reductive environment can result in triggered drug release profiles. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl- 2-H-tetrazolium bromide (MTT) assay in vitro showed no significant cytotoxicity as NIH 3T3 cells incubated in the micelles even when the concentrations up to 1000 μg/mL. Additionally fluorescence microscopy measurements and MTT assay demonstrated that the micelles exhibited a faster drug release and higher cellular proliferation inhibition due to the effect of intracellular reduction responsiveness compared with that of diblock copolymers. The above results suggest that the reduction-responsive, biodegradable and biocompatibility micelles could provide a platform to construct potential drug delivery systems for cancer therapy.

A reductive tri-block copolymer PEG-SS-PLA-SS-PEI with a double disulphide linkage in the backbone directed by H-bonding association was synthesized and self-assembled into cationic polymeric nanomicellar particles for in vivo antimiRNA delivery with an average diameter of 68 nm and a zeta potential of approximately 39 mV. The chemical structure of the copolymer was well characterized by 1H NMR and GPC. The cationic polymeric nanomicellar particles could be unpacked in an intracellular reductive environment (GSH) leading to the release of encapsulated antimiRNA. MTT assays in vitro showed no significant cytotoxicity of SGC7901 gastric cancer cells incubated with PEG-SS-PLA-SS-PEI micelles. The in vitro study indicated that the micelle-based antimiR-21 delivery system could effectively facilitate cellular uptake and greatly down-regulate the expression level of miR-21 in SGC7901 cell lines, which was comparable to Lipofectamine™ 2000. The down regulation of miR-21 remarkably induced apoptosis, suppressed the tumor cell migration and invasion, and increased the expression of target genes such as phosphatase and tensin homolog deleted on chromosome ten (PTEN) and Programmed Cell Death Protein 4 (PDCD4). More importantly, the in vivo systemic administration of the micelles/antimiR-21 complex in a gastric cancer model significantly inhibited tumor growth and increased the expression of target genes. The nanoparticle based on the PEG-SS-PLA-SS-PEI copolymer would be a safe and efficient carrier for delivery of therapeutic antimiRNA, which shows a prospective therapy method in gastric cancer.

Fluorescence imaging in the second near-infrared (NIR-II) window holds impressive advantages of enhanced penetration depth and improved signal-to-noise ratio. Bright NIR-II fluorophores with renal excretion ability and low tissue accumulation are favorable for in vivo molecular imaging applications as they can render the target-mediated molecular imaging process easily distinguishable. Here, a probe (anti-PD-L1-BGP6) comprising a fluorophore (IR-BGP6) covalently bonded to the programmed cell death ligand-1 monoclonal antibody (PD-L1 mAb) for molecular imaging of immune checkpoint PD-L1 (a targeting site upregulated in various tumors for cancer imaging) in the NIR-II window is reported. Through molecular optimization, the bright NIR-II fluorophore IR-BGP6 with fast renal excretion (≈91% excretion in general through urine within the first 10 h postinjection) is developed. The conjugate anti-PD-L1-BGP6 succeeds in profiling PD-L1 expression and realizes efficient noninvasive molecular imaging in vivo, achieving a tumor to normal tissue (T/NT) signal ratio as high as ≈9.5. Compared with the NIR-II fluorophore with high nonspecific tissue accumulation, IR-BGP6 derived PD-L1 imaging significantly enhances the molecular imaging performance, serving as a strong tool for potentially studying underlying mechanism of immunotherapy. The work provides rationales to design renal-excreted NIR-II fluorophores and illustrate their advantages for in vivo molecular imaging.

A super-contrast NIR-II fluorophore IR-BEMC6P with enhanced quantum yield is developed and the excretion mechanism is identified., In vivo molecular imaging in the “transparent” near-infrared II (NIR-II) window has demonstrated impressive benefits in reaching millimeter penetration depths with high specificity and imaging quality. Previous NIR-II molecular imaging generally relied on high hepatic uptake fluorophores with an unclear mechanism and antibody-derived conjugates, suffering from inevitable nonspecific retention in the main organs/skin with a relatively low signal-to-background ratio. It is still challenging to synthesize a NIR-II fluorophore with both high quantum yield and minimal liver-retention feature. Herein, we identified the structural design and excretion mechanism of novel NIR-II fluorophores for NIR-II molecular imaging with an extremely clean background. With the optimized renally excreted fluorophore–peptide conjugates, superior NIR-II targeting imaging was accompanied by the improved signal-to-background ratio during tumor detection with reducing off-target tissue exposure. An unprecedented NIR-II imaging-guided microsurgery was achieved using such an imaging platform, which provides us with a great preclinical example to accelerate the potential clinical translation of NIR-II imaging.

The significantly reduced tissue autofluorescence and scattering in the NIR-II region (1000-1700 nm) opens many exciting avenues for detailed investigation of biological processes in vivo. However, the existing NIR-II fluorescent agents, including many molecular dyes and inorganic nanomaterials, are primarily focused on complicated synthesis routes and unknown immunogenic responses with limited potential for clinical translation. Herein, the >1000 nm tail emission of conventional biocompatible NIR cyanine dyes with emission peaks at 700-900 nm is systematically investigated, and a type of bright dye for NIR-II imaging with high potential for accelerating clinical translation is identified. The asymmetry of the π domain in the S1 state of NIR cyanine dyes is proven to result in a twisted intramolecular charge-transfer process and NIR-II emission, establishing a general rule to guide future NIR-I/II fluorophore synthesis. The screened NIR dyes are identified to possess a bright emission tail in the NIR-II region along with high quantum yield, high molar-extinction coefficient, rapid fecal excretion, and functional groups amenable for bioconjugation. As a result, NIR cyanine dyes can be used for NIR-II imaging to afford superior contrast and real-time imaging of several biological models, facilitating the translation of NIR-II bioimaging to clinical theranostic applications.

A folic acid (FA) conjugated chitosan oligosaccharide (CSO) polylactic acid (PLA) copolymer FA-CSO-PLA with double disulphide linkage in the backbone directed by H-bonding association duplex was synthesized, and its self-assembled micelles were evaluated as smart targeted drug delivery carriers. Both of the intermediates and the terminal copolymers were characterized by 1H-NMR and gel permeation chromatography (GPC). The critical micelle concentration (CMC) value is 0.045 mg mL−1 which suggests the micelles are highly stable in dilute solution. TEM and DLS further confirmed the successful formation of micelles with an average size of 61 and 100 nm, PDI of 0.209 and 0.230 for blank and DOX loaded micelles, respectively. The micelles were destructed under a reductive environment, leading to encapsulated drug release. Moreover, fluorescence microscopy demonstrated that the micelles exhibited both a passive and active targeting ability in HeLA cells due to an EPR effect and folate-mediated endocytosis. These results suggested the micelles would provide a favourable platform for constructing excellent drug delivery systems for cancer therapy.

Fluorescence imaging multiplicity of biological systems is an area of intense focus, currently limited to fluorescence channels in the visible and first near-infrared (NIR-I; ∼700–900 nm) spectral regions. The development of conjugatable fluorophores with longer wavelength emission is highly desired to afford more targeting channels, reduce background autofluorescence, and achieve deeper tissue imaging depths. We have developed NIR-II (1,000–1,700 nm) molecular imaging agents with a bright NIR-II fluorophore through high-efficiency click chemistry to specific molecular antibodies. Relying on buoyant density differences during density gradient ultracentrifugation separations, highly pure NIR-II fluorophore-antibody conjugates emitting ∼1,100 nm were obtained for use as molecular-specific NIR-II probes. This facilitated 3D staining of ∼170-μm histological brain tissues sections on a home-built confocal microscope, demonstrating multicolor molecular imaging across both the NIR-I and NIR-II windows (800–1,700 nm).

Instructed by association units that allow reversible and unsymmetrical disulfide bond formation, hydrophilic (PEG) and hydrophobic (PLA) polymer chains are efficiently coupled into amphiphilic diblock copolymers. The desymmetrization of otherwise symmetrical reversible disulfide bond formation is achieved with amide association units that integrate both directional H-bonding and reversible disulfide bond formation, which ensure the connection of different polymer blocks while minimizing self-coupling. The resultant amphiphilic block copolymers self-assemble into long-lasting spherical micelles that are responsive to free thiols.

Developing smart nanocarriers for drug delivery system is advantageous for many kinds of successful biomedicinal therapy. In this study, we designed an amphiphilic block copolymers containing pH-responsive tetrahydropyran (THP) and tetrahydrofuran (THF) linkage. Their structures were confirmed by H-1 NMR and gel permeation chromatography (GPC). The release rate of encapsulated drugs depends upon the pH value and pH sensitive linkage in the backbone of copolymers. For PLA THP PEG micelles the cumulative relea,se amount of doxorubicin (DOX) was 62% at pH 5.0, which is about four times higher than that at pH 7.4. Under the same conditions the release rate for PLA THF PEG micelles is a little faster than that of the PLA THP PEG micelles. Cellular uptake study demonstrates that DOX-loaded micelles can easily enter the cells and produce the desired pharmacological action and minimizing the side effect of free DOX. These findings indicate that THP and THF linked diblock copolymer micelles is a promising candidate for drug carrier. (C) 2014 Elsevier Ltd. All rights reserved.

A new design for second near-infrared window (NIR-II) molecular fluorophores based on a shielding unit-donor-acceptor-donor-shielding unit (S-D-A-D-S) structure is reported. With 3,4-ethylenedioxy thiophene as the donor and fluorene as the shielding unit, the best performance fluorophores IR-FE and IR-FEP exhibit an emission quantum yield of 31% in toluene and 2.0% in water, respectively, representing the brightest organic dyes in NIR-II region reported so far.

In vivo molecular imaging of tumors targeting a specific cancer cell marker is a promising strategy for cancer diagnosis and imaging guided surgery and therapy. While targeted imaging often relies on antibody-modified probes, peptides could afford targeting probes with small sizes, high penetrating ability and rapid excretion. Recently, in vivo fluorescence imaging in the second near-infrared window (NIR-II, 1000–1700 nm) showed promise in reaching sub-centimeter depth with micron-scale resolution. Here, we report a novel peptide (named CP) conjugated NIR-II fluorescent probe for molecular tumor imaging targeting a tumor stem cell biomarker CD133. The click chemistry derived peptide-dye (CP-IRT dye) probe afforded efficient in vivo tumor targeting in mice with a high tumor-to-normal tissue signal ratio (T/NT > 8). Importantly, the CP-IRT probes were rapidly renal excreted (~ 87% excretion within 6 h), in stark contrast to accumulation in the liver for typical antibody-dye probes. Further, with NIR-II emitting CP-IRT probes, urethra of mice could be imaged fluorescently for the first time non-invasively through intact tissue. The NIR-II fluorescent, CD133 targeting imaging probes are potentially useful for human use in the clinic for cancer diagnosis and therapy.

Greatly reduced scattering in the second near-infrared (NIR-II) region (1000-1700 nm) opens up many new exciting avenues of bioimaging research, yet NIR-II fluorescence imaging is mostly implemented by using nontargeted fluorophores or wide-field imaging setups, limiting the signal-to-background ratio and imaging penetration depth due to poor specific binding and out-of-focus signals. A newly developed high-performance NIR-II bioconjugate enables targeted imaging of a specific organ in the living body with high quality. Combined with a home-built NIR-II confocal set-up, the enhanced imaging technique allows 900 µm-deep 3D organ imaging without tissue clearing techniques. Bioconjugation of two hormones to nonoverlapping NIR-II fluorophores facilitates two-color imaging of different receptors, demonstrating unprecedented multicolor live molecular imaging across the NIR-II window. This deep tissue imaging of specific receptors in live animals allows development of noninvasive molecular imaging of multifarious models of normal and neoplastic organs in vivo, beyond the traditional visible to NIR-I range. The developed NIR-II fluorescence microscopy will become a powerful imaging technique for deep tissue imaging without any physical sectioning or clearing treatment of the tissue.

A cleavable azo linker was synthesized and reacted with 5-(6)-carboxytetramethyl rhodamine succinimidyl ester, followed by further reactions with di(N-succinimidyl) carbonate and 5-(3-amino-1-propynyl)-2'-deoxyuridine 5'-triphosphate [dUTP(AP3)] to obtain the terminal product dUTP-azo linker-TAMRA as a potential reversible terminator for DNA sequencing by synthesis with no need for 3'-OH blocking.

Redox-responsive micelles self-assembled from dynamic covalent block copolymers with double disulfide linkage in the backbone have been developed successfully. The amphiphilic block copolymers PEG-PLA associated with complementary H-bonding sequences can self-assemble into spherical micelles in aqueous media with sizes from 34 nm to 107 nm with different molar mass of PEG and PLA. Moreover, in vitro drug release analyses indicate that reductive environment can result in triggered drug release profiles. The glutathione (GSH) mediated intracellular drug delivery was investigated against HeLa human cervical carcinoma cell line. Flow cytometry and fluorescence microscopy measurements demonstrated that the micelles exhibited faster drug release in glutathione monoester (GSH-OEt) pretreated HeLa cells than that in the nonpretreated cells. Cytotoxicity assay of DOX-loaded micelles indicated the higher cellular proliferation inhibition against 10 mM of GSH-OEt pretreated HeLa cells than that of the nonpretreated ones. These reduction-responsive, biodegradable and biocompatibility micelles could provide a favorable platform to construct excellent drug delivery systems for cancer therapy.