Red Emissive Biocompatible Nanoparticles from Tetraphenylethene‐Decorated BODIPY Luminogens for Two‐Photon Excited Fluorescence Cellular Imaging and Mouse Brain Blood Vascular Visualization

BODIPY (4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene) is an emissive chromophore in solutions but suffers from fluorescence quenching when aggregated due to its flat molecular conformation and small Stokes shift. To create aggregate‐state emissive BODIPY luminogens, tetraphenylethene (TPE), which is a popular luminogen with intriguing aggregation‐induced emission (AIE) characteristic, is introduced as periphery to a methylated BODIPY core. Three TPE‐BODIPY adducts are synthesized and characterized, and their photophysical properties and electronic structures are investigated. The incorporation of AIE‐active TPE units alleviates aggregation‐caused quenching of BODIPY core, furnishing emissive nanoparticles based on TPE‐BODIPY adducts. Significantly, the two‐photon absorption (TPA) and two‐photon excited fluorescence (TPEF) properties are improved as more TPE units are attached. The luminogens with 3TPE units (3TPE‐BODIPY) shows the strongest TPA and TPEF in the wavelength range of 750–830 nm, with cross‐section values of 264 and 116 GM at 810 nm, respectively. Red emissive nanoparticles with a Stokes shift of 60 nm and a fluorescence quantum yield of 16% are attained by encapsulating 3TPE‐BODIPY with 1,2‐sistearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethylene glycol)‐2000]. The nanoparticles are biocompatible and function well in TPEF cellular imaging and mouse brain blood vascular visualization.     

Synthesis of Blue‐, Green‐, Yellow‐, and Red‐Emitting Graphene‐Quantum‐Dot‐Based Nanomaterials with Excitation‐Independent Emission

A one‐pot method is described for the preparation of graphene quantum dots/graphene oxide (GQDs/GO) hybrid composites with emission in the visible region, through heteroatom doping and hydroxyl‐radical‐induced decomposition of GO. The NH₄OH‐ and thiourea‐mediated dissociation of H₂O₂ produces hydroxyl radicals. Treatment of GO with hydroxyl radicals results in the production of small‐sized GO sheets and GQDs, which self‐assemble to form GQDs/GO through strong π–π interactions. For example, the reaction of GO with a mixture of NH₄OH and H₂O₂ for 40, 120, and 270 min generates yellow‐emitting GQDs/GO (Y‐GQDs/GO), green‐emitting GQDs/GO, and blue‐emitting GQDs, while red‐emitting GQDs/GO (R‐GQDs/GO) are prepared by incubating GO with a mixture of thiourea and H₂O₂. From the analysis of these four GQD‐based nanomaterials by transmission electron microscopy, atomic force microscopy, and fluorescence lifetime spectroscopy, it is found that this tunable fluorescence wavelength results from the differences in particle size. All four GQD‐based nanomaterials exhibit moderate quantum yields (1–10%), nanosecond fluorescence lifetimes, and excitation‐independent emissions. Except for R‐GQDs/GO, the other three GQD‐based nanomaterials are stable in a high‐concentration salt solution (e.g., 1.6 m NaCl) and under high‐power irradiation, enabling the sensitive (high‐temperature resolution and large activation energy) and reversible detection of temperature change. It is further demonstrated that Y‐GQD/GO can be used to image HeLa cells.     

Enhancement of the 808 nm Photothermal Effect of Gold Nanorods by Thiol‐Induced Self‐Assembly

Gold (Au) nanomaterials are promising photothermal agents for the selective treatment of tumor cells owing to the strong capability to convert near‐infrared (NIR) irradiation into heat energy. One basic issue for practical photothermal therapy is the enhancement of photothermal effect in NIR region. Here, various low‐molecular‐weight thiols are applied to induce one‐dimensional (1D) self‐assembly of Au nanorods (NRs), which leads to the redshift of absorption peak towards NIR region. As a result, the 1D assembled Au NRs exhibit improved photothermal effect at 808 nm in comparison to unassembled Au NRs.     

Synthesis,structural characterization,and spectroscopic properties of the ortho,meta, and para isomers of 8‐(HOCH2‐C6H4)‐BODIPY and 8‐(MeOC6H4)‐BODIPY

Fluorescent members of the 4, 4‐difluoro‐4‐bora‐3a, 4a‐diaza‐s‐indacene (BODIPY) family are widely used for a range of markers, dyes, and sensors. The capacity to substitute the basic framework is an attractive feature permitting a range of differently substituted materials to be formed. New isomeric BODIPYs, o‐, m‐, and p‐8‐[R‐C₆H₄]‐BODIPY (R = CH₂OH, 2a (o), 2b (m), 2c (p); R = OMe, 3a (o), 3b (m), 3c (p)), have been synthesized and characterized by nuclear magnetic resonance, absorbance and emission spectroscopy, and single crystal X‐ray diffraction. The o‐isomers have a very high quantum yield emission in non‐polar solvents, while the m‐ and p‐ analogs showed weak fluorescence under the same conditions. Spectroscopic analysis, as well as X‐ray structural characterization, suggested that substitution in the ortho‐position of the phenyl ring is sufficient to increase the steric hindrance and hence impede the rotation of the phenyl moiety about the 8C‐C axis, thereby favoring radiative compared to non‐radiative relaxation. Copyright © 2013 John Wiley & Sons, Ltd.     

Broad‐Band Time‐Resolved Near Infrared Spectroscopy in the TJ‐II Stellarator

First experimental results on broad‐band, time‐resolved Near Infrared (NIR;here loosely defined as covering from 750 to 1650 nm) passive spectroscopy using a high sensitivity InGaAs detector are reported for the TJ‐II Stellarator. Experimental set‐up is described together with its main characteristics, the most remarkable ones being its enhanced NIR response, broadband spectrum acquisition in a single shot, and time‐resolved measurements with up to 1.8 kHz spectral rate. Prospects for future work and more extended physics studies in this newly open spectral region in TJ‐II are discussed. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Photoswitchable Fluorescent Liquid Crystal Nanoparticles and Their Inkjet‐Printed Patterns for Information Encrypting and Anti‐Counterfeiting

Liquid crystal nanoparticles (LCNPs) with desirable multifunctionality are catching increasing attention due to their promising applications in various fields. However, reversible photoswitchable fluorescent LCNPs are not reported until now. Here, the first example of water‐dispersible, reversibly phototunable fluorescent LCNPs prepared through a miniemulsion polymerization technique is presented. The LCNPs mainly consist of an aggregation‐induced emission enhancement (AIEE)‐active dicyanodistyrylbenzene‐based monomer, a LC cross‐linking monomer, and a dithienylethene (DAE) derivative as a photochromic molecular switch. The fluorescence of the resultant LCNPs can be switched reversibly between bright (ON) and dark (OFF) states with a high contrast and excellent repeatability upon alternating irradiation of 365 nm UV light and visible light (λ > 450 nm). This observation could be attributed to ring‐opening/ring‐closing photoisomerization of the DAE structure on the basis of an intraparticle fluorescence resonance energy transfer process between the AIEE‐active monomer and DAE derivative. More importantly, the potential for aqueous dispersion of the photoswitchable fluorescent LCNPs as a security ink for information encryption and anti‐counterfeiting is further demonstrated. The results demonstrate that the reversible photoswitchable fluorescent LCNPs as multifunctional nanomaterials exhibit promising applications in photonic fields.     

Red/Near‐Infrared Emissive Metalloporphyrin‐Based Nanodots for Magnetic Resonance Imaging‐Guided Photodynamic Therapy In Vivo

Near‐infrared emissive (NIR) porphyrin‐implanted carbon nanodots (PCNDs or MPCNDs) are prepared by selectively carbonization of free base or metal complexes [M = Zn(II) or Mn(III)] of tetra‐(meso‐aminophenyl)porphyrin in the presence of citric acid. The as‐prepared nanodots exhibit spontaneously NIR emission, small size, good aqueous dispersibility, and favorable biocompatibility characteristic of both porphyrins and pristine carbon nanodots. The subcellular localization experiment of nanodots indicates a lysosome‐targeting feature. And the in vitro photodynamic therapy (PDT) results on HeLa cells indicate the nanodots alone have no adverse effect on tumor cells, but display remarkable photodynamic efficacy upon irradiation. Moreover, MnPCNDs containing paramagnetic Mn(III) ions, which possesses good biocompatibility, NIR luminescence, and magnetic resonance imaging and efficient singlet oxygen production, are further studied in magnetic resonance imaging‐guided photodynamic therapy in vivo.     

Enhanced Near‐Infrared Shielding and Light Scattering Using Surface‐Roughened Hybrid Hollow Microparticles Synthesized with Polymer and TiO2@Al(OH)3 for Cosmetic Applications

Some materials and their micro‐/nanostructures are explored to shield near‐infrared (NIR) light. However, the structural role of polymeric matrices in terms of the sensitivity to NIR light and the scattering/absorption characteristics of particles bearing inorganic colloids lack understanding. To understand this issue further, a polymer–inorganic hybrid microparticle is synthesized, where submicrometer‐sized TiO₂ core‐thin aluminium hydroxide shell colloids (TiO₂@Al(OH)₃) are dispersed in a roughened polymer hollow particle matrix. They exhibit higher light extinction at NIR frequencies and higher light scattering efficiencies in the NIR regions compared to hybrid solid microparticles and a simple mixture of inorganic and polymer hollow microparticles. Owing to these characteristics, a cosmetic formulation containing the roughened hybrid hollow microparticles effectively suppresses the increase in the temperatures of artificial skin upon the illumination of a simulated sunlight, without displaying skin whitening which is caused by including much inorganic colloids in the formulation. The present results are helpful to those who manipulate the optical characteristics of inorganic particles whose geometries are hardly tailored. The results are also practically helpful to those who want to block NIR light by reducing the amount of inorganic particles.     

Fabrication of Au nanorod‐coated Fe3O4 microspheres as SERS substrate for pesticide analysis by near‐infrared excitation

Au nanorods coated Fe3O4 (Fe₃O₄@NRs) microspheres were designed as functional surface‐enhanced Raman scattering substrate with a feature of magnetic property and used for detection of pesticide residues that are annually used in agriculture by near‐infrared (NIR) excitation. With this strategy, the Fe₃O₄ microspheres were synthesized by hydrothermal method and surface functionalized with polyethylenimine, and then coated with Au nanorods densely. The Raman spectra were carried out by NIR excitation and 4‐ATP was chosen as the probe molecule. The results showed a good SERS activity of the Fe₃O₄@NRs microspheres. Moreover, this substrate could be used for pesticide analysis by portable Raman spectrometer with NIR excitation. Especially, the microspheres could be transferred from pesticides contaminated fruits peel to specially cleaned glass slide with the aid of the external magnetic field, by which the strong fluorescence of the apple components can be avoided while performing the pesticide analysis of fruits peel. Copyright © 2015 John Wiley & Sons, Ltd.     

Near‐infrared surface‐enhanced Raman spectroscopy (NIR‐SERS) studies on oxyheamoglobin (OxyHb) of liver cancer based on PVA‐Ag nanofilm

A near‐infrared surface‐enhanced Raman spectroscopy (NIR‐SERS) method was employed for oxyheamoglobin (OxyHb) detection to develop a simple blood test for liver cancer detection. Polyvinyl alcohol protected silver nanofilm (PVA‐Ag nanofilm) used as the NIR‐SERS active substrate to enhance the Raman scattering signals of OxyHb. High quality NIR‐SERS spectrum from OxyHb adsorbed on PVA‐Ag nanofilm can be obtained within 16 s using a portable Raman spectrometer. NIR‐SERS measurements were performed on OxyHb samples of healthy volunteers (control subjects, n = 30), patients (n = 40) with confirmed liver cancer (stage I, II and III) and the liver cancer patients after surgery (n = 30). Meanwhile, the tentative assignments of the Raman bands in the measured NIR‐SERS spectra were performed, and the results suggested cancer specific changes on molecule level, including a decrease in the relative concentrations and the percentage of aromatic amino acids of OxyHb, changes of the vibration modes of the C_aH_m group and pyrrole ring of OxyHb of liver cancer patients. In this paper, principal component analysis (PCA) combined with independent sample T test analysis of the measured NIR‐SERS spectra separated the spectral features of the two groups into two distinct clusters with the sensitivity of 95.0% and the specificity of 85.7%. Meanwhile, the recovery situations of the liver cancer patients after surgery were also assessed using the method of discriminant analysis‐predicting group membership based on PCA. The results show that 26.7% surgeried liver cancer patients were distinguished as the normal subjects and 63.3% were distinguished into the cancer. Our study demonstrated great potentials for developing NIR‐SERS OxyHb analysis into a novel clinical tool for non‐invasive detection of liver cancers. Copyright © 2013 John Wiley & Sons, Ltd.     

Recent Advancements in Ln‐Ion‐Based Upconverting Nanomaterials and Their Biological Applications

Upconversion nanoparticles (UCNPs) convert low‐energy infrared (IR) or near‐infrared (NIR) photons into high‐energy emission radiation ranging from ultraviolet to visible through a photon upconversion process. In comparison to conventional fluorophores, such as organic dyes or semiconductor quantum dots, lanthanide‐ion‐doped UCNPs exhibit high photostability, no photoblinking, no photobleaching, low cytotoxicity, sharp emission lines, and long luminescent lifetimes. Additionally, the use of IR or NIR for excitation in such UCNPs reduces the autofluorescence background and enables deeper penetration into biological samples due to reduced light scattering with negligible damage to the samples. Because of these attributes, UCNPs have found numerous potential applications in biological and medicinal fields as novel fluorescent materials. Different upconversion mechanisms commonly observed in UCNPs, various methods that are used in their synthesis, and surface modification processes are discussed. Recent applications of Ln‐UCNPs in the biological and medicinal fields, including in vivo and in vitro biological imaging, multimodal imaging, photodynamic therapy, drug delivery, and antibacterial activity, are also presented.     

Human‐Serum‐Albumin‐Coated Prussian Blue Nanoparticles as pH‐/Thermotriggered Drug‐Delivery Vehicles for Cancer Thermochemotherapy

Constructing novel multimodal antitumor therapeutic nanoagents has attracted tremendous recent attention. In this work, a new drug‐delivery vehicle based on human‐serum‐albumin (HSA)‐coated Prussian blue nanoparticles (PB NPs) is synthesized. It is demonstrated that doxorubicin (DOX)/HSA is successfully loaded after in situ polymerization of dopamine onto PB NPs, and the PB@PDA/DOX/HSA NPs are highly compatible and stable in various physiological solutions. The NPs possess strong near‐infrared (NIR) absorbance, and excellent capability and stability of photothermal conversion for highly efficient photothermal therapy applications. Furthermore, a bimodal on‐demand drug release sensitively triggered by pH or NIR irradiation has been realized, resulting in a significant chemotherapeutic effect due to the preferential uptake and internalization of the NPs by cancer cells. Importantly, the thermochemotherapy efficacy of the NPs has been examined by a cell viability assay, revealing a remarkably superior synergistic anticancer effect over either monotherapy. Such multifunctional drug‐delivery systems composed of approved materials may have promising biomedical applications for antitumor therapy.     

BODIPY Fluorescent Chemosensor for Cu2+ Detection and Its Applications in Living Cells: Fast Response and High Sensitivity

Copper is an essential trace element for the proper functioning of organ and metabolic process in humans. However, both its excess and deficiency in the body can result in adverse health effects. A BODIPY containing 2,2′-bipyridyl group was synthesized and used as a fluorescent chemodosimeter for selective Cu2+ detection in mild condition. This BODIPY shows fast response (~1 min) and high sensitivity for Cu2+ in aqueous solution due to the photoinduced electron transfer from the excited state of fluorophore to the bipyridyl unit complexed to Cu2+. The fluorescence quenching mechanism revealed by MALDI-TOF Mass spectra showed one Cu2+ could coordinate with two BODIPY molecules, and this coordination is reversible. This simple BODIPY dyes also could be used for sensing the Cu2+ in living cell. This work contributes to extend the potential applications of BODIPY to the biological and environmental areas.     

Forensic and security applications of a long‐wavelength dispersive Raman system

A novel dispersive system operating at 1064‐nm excitation and coupled with transfer electron InGaAs photocathode and electron bombardment CCD technology has been evaluated for the analysis of drugs of abuse and explosives. By employing near‐IR excitation at 1064‐nm excitation wavelength has resulted in a significant damping of the fluorescence emission compared to 785‐nm wavelength excitation. Spectra of street samples of drugs of abuse and plastic explosives, which usually fluoresce with 785‐nm excitation, are readily obtained in situ within seconds through plastic packaging and glass containers using highly innovative detector architecture based upon a transfer electron (TE) photocathode and electron bombarded gain (EB) technology that allowed the detection of NIR radiation at 1064 nm without fluorescence interference. This dispersive near‐IR Raman system has the potential to be an integral part in the armoury of the forensic analyst as a non‐destructive tool for the in‐situ analysis of drugs of abuse and explosives. Copyright © 2015 John Wiley & Sons, Ltd.     

Simple near‐infrared photodetector based on charge transfer complexes formed in molybdenum oxide doped N,N′‐di(naphthalene‐1‐yl)‐N,N′‐diphenyl‐benzidine

We have demonstrated a simple near‐infrared (NIR) photodetector (PD) based on charge transfer complex (CTC) formed in molybdenum trioxide (MoO₃) doped N,N′‐di(naphthalene‐1‐yl)‐N,N′‐diphenyl‐benzidine (NPB), which shows a photocurrent of about 0.35 A/cm² at –3 V under 980 nm illumination. The existence of CTC formation promotes photocurrent generation which is investigated by comparison with MoO₃ doped 2‐methyl‐9,10‐di(2‐naphthyl)anthracene (MADN) film which has no CTC absorption. It can be evolved that this kind of simple‐structure photodetector has potential application in the near‐infrared (NIR) detection area. It is shown in this Letter that although both MoO₃ and NPB have larger energy gaps of about 3 eV and weak absorption in the NIR region, the charge transfer complexes formed by mixing the two materials show an extra absorption band and good photoelectric response in the NIR region.

     

Cross‐Linked Proteins with Gold Nanoclusters: A Dual‐Purpose pH‐Responsive Material for Controllable Cell Imaging and Antibiotic Delivery

This report describes the development of a facile method for the synthesis of cross‐linked proteins with gold nanoclusters (CP‐GNC). The synthesis reaction is completed within 15 min at 97 °C. The synthesized CP‐GNC are characterized by using UV–vis absorption, fluorescence, X‐ray photoelectron spectroscopy, and transmission electron microscopy. CP‐GNC are approximately 100 nm in diameter and 700 nm in length, whereas AuNCs within the nanorods are approximately 6 nm in size. These materials are highly fluorescent with quantum yield of 7.2% and can be absorbed onto and release from bacterial cells in a pH‐dependent and reversible manner. The recent data show that CP‐GNC can be a useful, new tool with potential applications in fluorescent cell imaging and antibiotic targeting.     

Core–Shell Bi2Se3@mSiO2‐PEG as a Multifunctional Drug‐Delivery Nanoplatform for Synergistic Thermo‐Chemotherapy with Infrared Thermal Imaging of Cancer Cells

Thermo‐chemotherapy combining photothermal therapy (PTT) with chemotherapy has become a potent approach for antitumor treatment. In this study, a multifunctional drug‐delivery nanoplatform based on polyethylene glycol (PEG)‐modified mesoporous silica‐coated bismuth selenide nanoparticles (referred to as Bi₂Se₃@mSiO₂‐PEG NPs) is developed for synergistic PTT and chemotherapy with infrared thermal (IRT) imaging of cancer cells. The product shows no/low cytotoxicity, strong near‐infrared (NIR) optical absorption, high photothermal conversion capacity, and stability. Utilizing the prominent photothermal effect, high‐contrast IRT imaging and efficient photothermal killing effect on cancer cells are achieved upon NIR laser irradiation. Moreover, the successful mesoporous silica coating of the Bi₂Se₃@mSiO₂‐PEG NPs cannot only largely improve the stability but also endow the NPs high drug loading capacity. As a proof‐of‐concept model, doxorubicin (DOX) is successfully loaded into the NPs with rather high loading capacity (≈50.0%) via the nanoprecipitation method. It is found that the DOX‐loaded NPs exhibit a bimodal on‐demand pH‐ and NIR‐responsive drug release property, and can realize effective intracellular drug delivery for chemotherapy. The synergistic thermo‐chemotherapy results in a significantly higher antitumor efficacy than either PTT or chemotherapy alone. The work reveals the great potential of such core–shell NPs as a multifunctional drug‐delivery nanosystem for thermo‐chemotherapy.     

Photothermally Responsive Inks for Inkjet‐Printing Secure Information

2D patterns of photothermally responsive near‐infrared (NIR) absorbing gold nanostars (GNS), coated with multiple charged polymer layers, are inkjet‐printed on a glass surface. The shape of the localized surface plasmon resonance (LSPR) NIR absorption bands in the printed patterns loses its peaked form due to plasmon coupling, unless GNS are enveloped in multiple coating layers, keeping the inter‐GNS distance sufficiently large. In the latter case, the photothermal temperature increase (ΔT) induced by the NIR laser irradiation follows a ΔT versus irradiation wavelength (λ_irr) profile with the same sharply peaked shape of the LSPR bands of the liquid ink. With this result, a new paradigm for inkjet‐writing secure information is introduced, as an alternative to the current methods based on direct visual inspection of printed patterns. While the printed ink patterns of GNS with different coatings are visually indistinguishable despite their different NIR absorption spectrum, their photothermal response changes dramatically with λ_irr. This allows either to write and read simple information using a single λ_irr (YES answer for ΔT > threshold) or to use multiple λ_irr to write and read complex information like thermal bar codes and anti‐counterfeit signatures.     

NIR‐Triggered Release of Nitric Oxide with Upconversion Nanoparticles Inhibits Platelet Aggregation in Blood Samples

There is a great challenge to overcome the limitation of tissue penetration depth, while maximizing the benefit of light‐triggered biochemical cascades in a well‐defined mode simultaneously. Here, a new method of near‐infrared (NIR) light‐triggered release of nitric oxide (NO) by developing upconversion nanoparticles (UCNPs)‐based conjugate chemistry is reported. As the key nanotransducer in the design, core–shell‐structured UCNPs are encapsulated with a layer of SiO₂ and then covalently linked with a potent NO‐releasing donor (S‐nitroso‐N‐acetyl‐dl ‐penicillamine, SNAP). It is featured with highly localized breakage of chemical bonds of SNAP molecules by NIR–UV upconversion, enabling simultaneous NO release in a light dosage‐dependent manner. The biological effects of NO releasing are demonstrated by cellular imaging and inhibition of platelet aggregation from blood samples. This work provides a flexible and robust platform to generate cell‐signaling gas molecules trigged by NIR laser with deep tissue penetration.     

Photothermal/Photodynamic Therapy with Immune‐Adjuvant Liposomal Complexes for Effective Gastric Cancer Therapy

A diagnosis and therapeutic strategy for gastric cancer is developed herein by combining thermosensitive liposomal (TSL)‐based photothermal/photodynamics therapy (PTT/PDT) with chemotherapy and adjuvant immunotherapy. IR820, a photothermal agent, paclitaxel (PTX), an antitumor drug, and imiquimod (R837), a Toll‐like‐receptor‐7 agonist, are coencapsulated into a TSL drug delivery system. These formed PTX‐R837‐IR820@TSL complexes exhibit excellent optical properties, good dispersibility, and stability. Under NIR light irradiation, the measurement of singlet oxygen production and thermal efficiency indicate promising potential of PTX‐R837‐IR820@TSL complexes for PTT and PDT. Confocal microscopy and small animal NIR imaging demonstrate tumor targeting ability of the liposomal complexes to gastric cancer cells. In vitro cell viability assays and in vivo animal experiments show prominent antitumor efficiency of PTX‐R837‐IR820@TSL complexes upon NIR light irradiation. This excellent therapeutic efficacy is attributed to the simultaneous chemotherapy and PTT/PDT. Furthermore, the liposomal complexes under NIR irradiation would ablate tumors to generate a pool of tumor‐associated antigens, which is able to promote strong antitumor immune responses in the presence of those R837‐containing liposomal complexes acted as adjuvant. These results indicate that the multifunctional liposomal complexes could realize a remarkable synergistic therapeutic outcome in gastric carcinoma.