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We demonstrate tunable lifetimes (sub-milliseconds and seconds) at the same emission wavelength of a material, along with an abrupt intensity change between the two emission states. Based on this stepped photon emission material, a time-domain stepwise encoding method is developed and applied to point-of-care testing with an ultra-large quantitative detection range.

Single molecule localization microscopy based on photoactivation is a powerful tool for investigating the ultrastructure of cells. We developed a general strategy for photoactivatable fluorophores, using 2,3-dihydro-1,4-oxathiine group (SO) as a tag to attach to various skeletal structures, including coumarin, BODIPY, rhodamine, and cyanine. The conjugation of SO resulted in a significant loss of fluorescence due to photoinduced electron transfer (PeT). Under the irradiation of excitation light, singlet oxygen generated by the fluorophores converted the SO moiety into its ester derivative, terminated the PeT process, and restored the fluorescence. Single molecule localization imaging was achieved using a dual functional illuminating beam in the visible, acting as both the activating and the exciting source. We successfully applied these photoactivatable probes for time-lapse super-resolution tracking in living cells and super-resolution imaging of microtubule structures in neurons.

Luminescence nanothermometry makes non-invasive and real-time temperature readings possible in living animals. However, the spectral fluctuation in tissues and fluids, as well as the interaction between fluorophores and environment hinders accuracy of the thermometry. Here, we report a luminescence lifetime-based nanothermometry which specifically addresses this problem. A temporal based calibration (lifetime sensing) in the NIR range, an endogenous thermal response as well as a polymer encapsulation evading environmental factors, altogether help to pinpoint temperature in vivo. Thanks to the highly condensed Nd-Yb ions in a well-protected tiny core-shell nanocrystal (overall 11 nm), a temperature sensitivity about 2.07% K−1 (with 5% Yb3+ doped nanoparticles) and an accuracy of 0.27 K (with 25% Yb3+ doped nanoparticles) in biological fluids are achieved. Hopefully, combining thermally activated energy transfer nanothermometer with anti-interference lifetime thermometry would provide a more accurate temperature measurement for biological and preclinical studies.

Afterglow materials have drawn considerable attention due to their attractive luminescent properties. However, their low-efficiency luminescence in aqueous environment limits their applications in life sciences. Here, we developed a molecular fusion strategy to improve the afterglow efficiency of photochemical afterglow materials. By fusing a cache unit with an emitter, we obtained a blue afterglow system with a quantum yield up to 2.59 %. This is 162 times higher than that achieved with the traditional physical mixing system and more than an order of magnitude larger than that of the covalent coupling system. High-efficiency afterglow nanoparticles were obtained and utilized for bio-imaging with a high signal-to-noise ratio (SNR) of 131, and for the lateral flow immunoassay (LFIA) of β-hCG with a low limit of detection (LOD) of 0.34 mIU mL

We developed a luminescence lifetime-based nanothermometer with a single-exponential luminescence decay in the ∼s time scope via a photochemical reaction. The luminescence lifetime imaging in vivo can be performed on an EMCCD and consumer-grade camera, which significantly reduces the technical threshold of luminescence lifetime imaging.

Temperature as a typical parameter, which influences the status of living creatures, is essential to life activities and indicates the initial cellular activities. In recent years, the rapid development of nanotechnology provides a new tool for studying temperature variation at the micro- or nano-scales. In this study, an important phenomenon is observed at the cell level using luminescent probes to explore intracellular temperature changes, based on Yb-Er doping nanoparticles with special upconversion readout mode and intensity ratio signals (I

Transcatheter arterial embolization (TAE) is wildly used in clinical treatments. However, the online monitoring of the thrombosis formation is limited due to the challenges of the direct visualization of embolic agents and the real-time monitoring of dynamic blood flow. Thus, we developed a photochemical afterglow implant with strong afterglow intensity and a long lifetime for embolization and imaging. The liquid pre-implant injected into the abdominal aorta of mice was rapidly transformed into a hydrogel in situ to embolize the blood vessel. The vascular embolism position can be observed by the enhanced afterglow of the fixed implant, and the long lifetime of afterglow can also be used to monitor the effect of embolization. This provides an excellent candidate in bio-imaging to avoid the autofluorescence interference from continuous light excitation. The study suggests the potential usefulness of the implant as an embolic agent in TAE and artery imaging during a surgical procedure.

Exploiting the energy transfer (ET) direction is important in nanoscale fluorescent detection systems. In a typical detection system based on ET, the quenching efficiency was evaluated by decrease of donor's emission intensity, but there exists reabsorption process apart from nonradiative ET process. Here, we propose a method to analyze the individual contribution of nonradiative ET and reabsorption to quenching efficiency. These two processes influence in a different way on the nanoplatform consisting of NaYF4:20%Yb,2%Er UCNPs and a sulfonyl modified cyanine dye. We find that nonradiative ET process contributes more than reabsorption and possesses a better detection sensitivity (2.27 folds). Our work presents a thorough understanding of detection process, which will be conducive in evaluating the sensitivity of similar detection systems.

Luminescence imaging, exhibiting noninvasive, sensitive, rapid, and versatile properties, plays an important role in biomedical applications. It is usually unsuitable for direct biodetection, because the detected luminescence intensity can be influenced by various factors such as the luminescent substance concentration, the depth of the luminescent substance in the organism, etc. Ratiometric imaging may eliminate the interference due to the luminescent substance concentration on the working signal. However, the conventional ratiometric imaging mode has a limited capacity for in vivo signal acquisition and fidelity due to the highly variable and wavelength-dependent scattering and absorption process in biotissue. In this work, we demonstrate a general imaging mode in which two signals with the same working wavelength are used to perform ratiometric sensing ignoring the depth of the luminescent substance in the organism. Dual-channel decoding is achieved by time-gated imaging technology, in which the signals from lanthanide ions and fluorescent dyes are distinguished by their different luminescent lifetimes. The ratiometric signal is proven to be nonsensitive to the detection depth and excitation power densities; thus, we could utilize the working curve measured in vitro to determine the amount of target substance (hypochlorous acid) in vivo., A time-gated ratiometric detection mode with the same working wavelength could minimize the interferences from photon attenuation, which makes sense for in vivo detection.

Time-resolved fluorescence lifetime imaging (FLIM) in the near-infrared region of 900–1700 nm not only allows a deep tissue penetration depth but also offers the unique benefit of the quantitative visualization of molecular events in vivo and is independent of local luminescence intensity and fluorophore concentration. Herein, we report the design of a wide-range pH sensitive molecular probe based on Yb3+ porphyrinate. The Yb3+ probe shows increasing NIR emission and lifetime with pKa values of ca. 6.6 from pH 9.0 and 5.0 and also displays an elongated lifetime from ca. 135 to 170 μs at lower pH values (5.0–1.0) due to aggregation and reduced exposure to water at low pH values. Importantly, the probe is able to monitor a wide range of in vivo gastrointestinal pH values in mice models and the potential applications in imaging-guided gastrointestinal diagnostics and therapeutics were revealed. This study shows that lifetime contrast is important for preclinical imaging; lanthanide complexes could be successfully used in the design of stimuli-responsive NIR τ probes for advanced in vivo imaging.

Creating a security label that carries entirely distinct information in reflective and fluorescent states would enhance anti-counterfeiting levels to deter counterfeits ranging from currencies to pharmaceuticals, but has proven extremely challenging. Efforts to tune the reflection color of luminescent materials by modifying inherent chemical structures remain outweighed by substantial trade-offs in fluorescence properties, and vice versa, which destroys the information integrity of labels in either reflection or fluorescent color. Here, a strategy is reported to design geminate labels by programming fluorescent cholesteric liquid crystal microdroplets (two-tone inks), where the luminescent material is ‘coated’ with the structural color from helical superstructures. These structurally defined microdroplets fabricated by a capillary microfluidic technique contribute to different but intact messages of both reflective and fluorescent patterns in the geminate labels. Such two-tone inks have enormous potential to provide a platform for encryption and protection of valuable authentic information in anti-counterfeiting technology., Creating an enhanced-security-level label that carries entirely distinct information in different optical states has proven challenging. Here, the authors design geminate labels by programming fluorescent cholesteric liquid crystal microdroplets to encrypt fluorescent security information behind colorful reflective patterns.

We demonstrate a 3,5-di(p-oxethyl)styryl conjugated BODIPY showing deep-red upconversion luminescence with a high efficiency of 16.6%. Furthermore, water-soluble BODIPY-doped upconversion nanoparticles with efficiency up to 6.9% under low excitation power density (∼1 mW cm−2) are developed and enable high-performance bioimaging in vivo.

Porphyrins are endogenous photosensitizers, which are widely present in living systems. Endogenous porphyrins in the human body are mainly the precursors for heam biosynthesis. However, excessive porphyrins can lead to syndrome porphyria, causing skin photosensitivity and damage, anemia, hepatotoxicity, or organ failure. Traditional detection techniques include spectrometry and high performance liquid chromatography (HPLC). Without any pretreatment, they can hardly determine the level of porphyrins in whole blood. Therefore, it's significantly important to realize highly efficient detection of porphyrins. In this work, we proposed a superlong afterglow reporter to realize easy and rapid detection for porphyria. The molecular afterglow reporters can respond to singlet oxygen (1O2) produced by porphyrins, and the detection signals can be received by the emission of afterglow reporters. During the detection process, afterglow signals can avoid the autofluorescence and scattering of complex biological system to reduce the interference of background noise. Our study demonstrates that superlong afterglow reporter is a promising technique for efficient and accurate detection of porphyria and has a great potential in clinical detection.

A water-soluble phosphorescent bioprobe was successfully developed by introducing an iridium(III) complex as a phosphorescent signaling unit with poly(N-isopropylacrylamide) (PNIPAM) as the stimuli-responsive backbone. The probe was used for the effective detection of cysteine (Cys)/homocysteine (Hcy) and temperature based on changes in the phosphorescence signal. The design principle was based on the fact that the aldehyde groups in the cyclometalated ligands of the iridium(III) complex moiety can react with the β- or γ-aminothiol group to form thiazolidine or thiazinane, respectively, resulting in a phosphorescence change in the iridium(III) complex, thereby facilitating the detection of Cys and Hcy. Moreover, a phosphorescent hydrogel based on this probe was formed upon cross-linking and was then used as a quasi-solid sensing system for detecting Cys and Hcy. Furthermore, by using a time-resolved photoluminescence technique, the probe can detect Hcy in the presence of intense background fluorescence. In addition, phase changes in temperature-responsive PNIPAM can result in a switch of microenvironment between hydrophilicity and hydrophobicity, to which the phosphorescent emission of the iridium(III) complex is very sensitive. This bioprobe integrates water solubility, biocompatibility, and sensing capability into one system, which is advantageous for biological applications. Further investigation of the application of the bioprobe for living-cell imaging confirmed that the probe is membrane permeable and is capable of detecting Cys in living cells with notable phosphorescence enhancement. Fluorescence lifetime imaging microscopy is successfully applied for sensing and bioimaging of intracellular Cys in the presence of short-lived background fluorescence.

Gemcitabine (GEM) has been the recommended first-line drug for patients with pancreatic ductal adenocarcinoma cancer (PDAC) for the last twenty years. However, GEM-based treatment has failed in many patients because of the drug resistance acquired during tumorigenesis and development. To override resistance to GEM in pancreatic cancer, we developed a visualisable, photothermally controlled, drug release nanosystem (VPNS). This nanosystem has NaLuF4:Nd@NaLuF4 nanoparticles as the luminescent core, octabutoxyphthalocyanine palladium(II) (PdPc) as the photothermal agent, and phosphorylated gemcitabine (pGEM) as the chemodrug. pGEM, one of the active forms of GEM, can circumvent the insufficient activation of GEM in cancer cell metabolism. The NaLuF4:Nd@NaLuF4 nanoparticles were employed to visualise the tumor lesion in vivo by their near-infrared luminescence. The near-infrared light-triggered photothermal effect from PdPc could trigger the release of pGEM loaded in a thermally responsive ligand and simultaneously enable photothermal cancer treatment. This work presents an effective method that suppresses the growth of tumour cells with dual-mode treatment and enables the improved treatment of orthotopic nude mice afflicted with pancreatic cancer.

Nd doped nanoparticles is commonly used as bioimaging agents but presents poor stability. Here, a polymer coating is applied to NaYF4:Nd nanoparticles using a versatile step-by-step coating strategy. The as-synthesized NaYF4:Nd@NaLuF4@SiO2@PS colloids show good stability in various polar solvent and are very stable in water at least for 6 months. These NaYF4:Nd@NaLuF4@SiO2@PS colloids can exhibit strong down converting photoluminescence when excited by 808 nm lasers. Moreover, these NaYF4:Nd@NaLuF4@SiO2@PS colloids accumulate in liver of mice when used as bio-imaging agents, which exhibit strong fluorescence luminescence in NIR II window.

In this article, a facile strategy is developed to synthesize a nanocomposite containing both a rare earth doped upconversion nanoparticle (RE-UCNP) and gold nanoparticles (GNPs). Such a nanocomposite can serve as a dual-modal imaging agent for upconversion luminescence (UCL) imaging and photoacoustic tomography (PAT). High spatial resolution, 3-dimensional imaging of blood vessels could be achieved with the RE-UCNP/GNPs@SiO2 nanocomposite by PAT, while UCL imaging offers a high-speed, low-interference and 2-dimensional imaging mode.

Colorectal cancer is a leading cause of death worldwide. Accurate diagnosis and evaluation of malignant extent are crucial for disease treatment. In order to improve the current limited effectiveness of agents for the current theranostics of this disease, we selected upconversion nanoparticles (UCNPs) as an alternative agent, due to their unique luminescence properties. Considering tumorigenesis in the abdominal cavity, intraperitoneal (IP) administration is utilized, based on spatial proximity. Accordingly, citrate-modified UCNPs (cit-UCNPs) were synthesized and injected into mice via the IP route, compared with the IV route. The results demonstrated that cit-UCNPs following IP administration encountered significantly different biological processes from those following IV administration. Cit-UCNPs intraperitoneally injected primarily accumulated in the organs in the abdominal cavity, including the pancreas and the mesentery, while the intravenously injected UCNPs mainly gathered in the liver and the spleen. Through the IP route, the majority of cit-UCNPs accumulated in the cancerous cecum tissues, while the minority gathered in the normal cecum tissues. Consequently, cit-UCNPs administrated via the IP route to treat colorectal cancer are superior for clinical applications.

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".

For years, luminescence lifetime imaging has served as a quantitative tool in indicating intracellular components and activities. However, very few studies involve the in vivo study of animals, especially in vivo stimuli-responsive activities of animals, as both excitation and emission wavelengths should fall into the near-infrared (NIR) optical transparent window (660-950 and 1000-1500 nm). Herein, this work reports a lifetime-responsive nanocomposite with both excitation and emission in the NIR I window (800 nm) and lifetime in the microsecond region. The incorporation of Tm3+ -doped rare-earth nanocrystals and NIR dye builds an efficient energy transfer pathway that enables a tunable luminescence lifetime range. The NaYF4 :Tm nanocrystal, which absorbs and emits photons at the same energy level, is found to be 33 times brighter than optimized core-shell upconversion nanocrystals, and proved to be an effective donor for NIR luminescence resonance energy transfer (LRET). The anti-interference capability of luminescence lifetime signals is further confirmed by luminescence and lifetime imaging. In vivo studies also verify the lifetime response upon stimulation generated in an arthritis mouse model. This work introduces an intriguing tool for luminescence lifetime-based sensing in the microsecond region.

Sactionine-containing antibiotics (sactibiotics) are a growing class of peptide antibiotics belonging to the ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily. We report the characterization of thuricin Z, a novel sactibiotic from Bacillus thuringiensis. Unusually, the biosynthesis of thuricin Z involves two radical S-adenosylmethionine (SAM) enzymes, ThzC and ThzD. Although ThzC and ThzD are highly divergent from each other, these two enzymes produced the same sactionine ring in the precursor peptide ThzA in vitro. Thuricin Z exhibits narrow-spectrum antibacterial activity against Bacillus cereus. A series of analyses, including confocal laser scanning microscopy, ultrathin-sectioning transmission electron microscopy, scanning electron microscopy, and large-unilamellar-vesicle-based fluorescence analysis, suggested that thuricin Z binds to the bacterial cell membrane and leads to membrane permeabilization.

The in vivo temperature monitoring of a microenvironment is significant in biology and nanomedicine research. Luminescent nanothermometry provides a noninvasive method of detecting the temperature in vivo with high sensitivity and high response speed. However, absorption and scattering in complex tissues limit the signal penetration depth and cause errors due to variation at different locations in vivo. In order to minimize these errors and monitor temperature in vivo, in the present work, we provided a strategy to fabricate a same-wavelength dual emission ratiometric upconversion luminescence nanothermometer based on a hybrid structure composed of upconversion emissive PbS quantum dots and Tm-doped upconversion nanoparticles. The ratiometric signal composed of two upconversion emissions working at the same wavelength, but different luminescent lifetimes, were decoded via a time-resolved technique. This nanothermometer improved the temperature monitoring ability and a thermal resolution and sensitivity of ~0.5 K and ~5.6% K−1 were obtained in vivo, respectively., Traditional ratiometric temperature monitoring is challenging due to the variation in tissue absorption and scattering of different wavelengths. Here, the authors show improved accuracy by using emission at the same wavelength, but different luminescent lifetimes decoded by a time-resolved technique.

Optical encryption with easy operation, multichannel and high security has been one of the most significant technologies for information security. Stimuli-responsive luminescent materials have emerged as an ideal candidate for optical encryption, owing to its smart responsive property and high security. Herein, a type of light-responsive multicolor luminescent materials for high-security information encryption, which are fabricated by combining sensitizer, consumption unit, and emitter is developed. Different types of sensitizers to achieve different stimulus light responses, and multicolor light-responsive luminescent can be obtained by varying the composition of perovskite nanocrystals emitter can be selected. Both stimulus light and emission color can be used as distinguishable encoding dimensions, which enable multiplexed encoding with high capacity and complexity. Importantly, the controllable consumption can be manipulated by varying the concentration of consumption unit, so the programmed information encoded in different channels can be selectively read and erased simultaneously by varying stimulus light. The method makes the encryption information highly resistive to brute force trial-and-error attacks, which achieves high security level of information protection.

We designed and synthesized a water-dispersible dye-sensitized upconversion nanocomposite with approximately 17 times enhancement of upconversion luminescence. The nanocomposite was successfully applied in lymphatic imaging for the first time as an application model.

Photooxidation is a major threat to perishable products. Therefore, an effective monitoring system for photooxidation reactions is urgently needed due to safety concerns. Herein, a time–oxygen & light indicator (TOLI) from a non-emissive stealth upconversion system is demonstrated to address this issue. Under photooxidation stress, a nonluminous precursor 9,10-bis(diphenylphosphino)anthracene (M1) is photo-oxidized to an efficient emitter 9,10-bis(diphenylphosphoryl)anthracene (M2), and triplet–triplet annihilation (TTA)-based upconversion emission is observed. The reaction rate is easily tunable and responsive to oxygen concentration and light intensity. Over a period of time, the enhanced emission related to the degree of photooxidation is ultimately used as an indicating signal. Thus a TOLI based on the TTA-upconversion process is achieved. This work not only develops a rational approach to the visualization and monitoring of photooxidation, but also demonstrates the varied control of the TTA-upconversion process.

The fluorescent probes working in the near-infrared (NIR) window have unparalleled advantages of a high penetration depth and low interference from autofluorescence. In this paper we introduced a rare-earth doped nanoprobe working in this region with a narrow emission band, a high efficiency, and good bio-compatibility. The newly-developed host material LiYF4 managed to strengthen the emission intensity and generate a fine structure of the emission peaks. After the optimization of the doping ratio of Nd3+ and surface modification, the LiYF4:5%Nd3+ probe could reach a penetration depth of 3-5 mm and could be successfully utilized in lymphatic imaging, with a signal-to-noise ratio of 14.8 in vivo and a resolution of ∼0.2 mm in circulatory imaging. This probe may be further used in bio-detection and the host material itself may replace the traditional NaYF4 in some aspects of applications.

Upconversion based on triplet-triplet annihilation (TTA-UC) has received much attention due to its unique ability to effectively harvest low-energy photons in the solar spectrum for widespread investigations involving energy, environment, and bioapplication. However, the utilization of conventional TTA-UC systems for low-power bioimaging in vivo is still a challenge due to their incompatibility and moderate efficiency in aqueous media. Herein, we pioneer the molecular modification strategy by introducing steric hindrance to the BODIPY annihilators to realize robust TTA-UC in biocompatible nanocapsule. The improved molecules could maintain excellent luminescence even at a very high concentration wherein the separation distance between neighbouring chromophores was reduced to facilitate the pivotal process of Dexter energy transfer. In this way, the encapsulated TTA-UC system became highly efficient in biological circumstance with quantum efficiency ФUC of 6.3%. Consequently, the constructed nanocapsule was capable of operating at low-power with high contrast for in vivo imaging.

Temperature is an essential factor that counts for living systems where complicated vital activities are usually temperature dependent. In vivo temperature mapping based on non-contact optical approach will be beneficial for revealing the physiological phenomena behind with minimized influence to the organism. Herein, a highly thermal-sensitive upconversion system based on triplet–triplet annihilation (TTA) mechanism is pioneered to indicate body temperature variation sensitively over the physiological temperature range. The temperature-insensitive NaYF4: Nd nanophosphors with NIR emission was incorporated into the temperature-responsive TTA-upconversion system to serve as an internal calibration unit. Consequently, a ratiometric thermometer capable of accurately monitoring the temperature changes in vivo was developed with high thermal sensitivity (~7.1% K−1) and resolution (~0.1 K)., Though luminescence imaging is a promising approach for contactless thermometry in vivo, the low thermal sensitivity of existing thermometers limits its potential. Here, the authors develop a high-sensitivity ratiometric nanothermometer based on triplet-sensitized upconversion.

Combinational administration of chemotherapy (CT) and photothermal therapy (PTT) has been widely used to treat cancer. However, the scheduling of CT and PTT and how it will affect the therapeutic efficacy has not been thoroughly investigated. The challenge is to realize the sequence control of these two therapeutic modes. Herein, we design a temperature sensitive upconversion nanocomposite for CT-PTT combination therapy. By monitoring the microscopic temperature of the nanocomposite with upconversion luminescence, photothermal effect can be adjusted to achieve thermally triggered combination therapy with a sequence of CT, followed by PTT. We find that CT administered before PTT results in better therapeutic effect than other administration sequences when the dosages of chemodrug and heat are kept at the same level. This work proposes a programmed method to arrange the process of combination cancer therapy, which takes full advantage of each therapeutic mode and contributes to the development of new cancer therapy strategies., The combination of chemo and photothermal therapy is widely used to treat cancer but control of chemo and thermal effects is needed for optimized treatment. Here, the authors describe an upconversion nanoparticle which can be used for controlled sequential treatment by controlling laser power.

Triplet-triplet annihilation upconversion (TTA-UC) has gained increasing attention because it allows for harvesting of low-energy photons in the solar spectrum with high efficiency in relevant applications including solar cells and bioimaging. However, the utilization of conventional TTA-UC systems for low-power bioapplications is significantly hampered by their general incompatibility and low efficiency in aqueous media. Herein we report a metal-organic framework (MOF) as a biocompatible nanoplatform for TTA-UC to realize low-power in vivo imaging. Our MOF consists of a porphyrinic sensitizer in an anthracene-based Zr-MOF as a TTA-UC platform. In particular, closely aligned chromophores in the MOF facilitate a long-range 3D triplet diffusion of 1.6 μm allowing efficient energy migration in water. The tunable ratio between sensitizer and annihilator by our synthetic method also allows an optimization of the system for maximized TTA-UC efficiency in water at a very low excitation power density. Consequently, the low-power imaging of lymph node in a live mouse was successfully demonstrated with an excellent signal-to-noise ratio (SNR > 30 at 5 mW cm-2).

A kind of fluorescent/phosphorescent dual-emissive conjugated polyelectrolyte has been prepared by introducing phosphorescent platinum(II) porphyrin (O2-sensitive) into a fluorene-based conjugated polyelectrolyte (O2-insensitive), which can form ultrasmall conjugated polymer dots (FP-Pdots) in the phosphate buffer solution (PBS) via self-assembly caused by their amphiphilic structures with hydrophobic backbones and hydrophilic side chains. These FP-Pdots can exhibit an excellent ratiometric luminescence response to O2 content with high reliability and full reversibility for measuring oxygen levels, and the excellent intracellular ratiometric O2 sensing properties of the FP-Pdots nanoprobe have also been confirmed by the evident change in the Ired/Iblue ratio values in living cells cultured at different O2 concentrations. To confirm the reliability of the O2 sensing measurements of the FP-Pdots nanoprobe, O2 quenching experiments based on lifetime measurements of phosphorescence from Pt(II) porphyrin moieties have also been carried out. Utilizing the sensitivity of the long phosphorescence lifetime from Pt(II) porphyrins to oxygen, the FP-Pdots have been successfully applied in time-resolved luminescence imaging of intracellular O2 levels, including photoluminescence lifetime imaging and time-gated luminescence imaging, which will evidently improve the sensing sensitivity and reliability. Finally, in vivo oxygen sensing experiments were successfully performed by luminescence imaging of tumor hypoxia in nude mice.

Inhomogeneous heating by photothermal therapy (PTT) during cancer treatment often results in the recurrence of tumors. Thus, integrating PTT with chemotherapy (CHT) may provide a complementary treatment for enhanced therapeutic efficiency. Herein, this study develops a hollow structured polymer-silica nanohybrid (HPSN) as a nanocarrier to simultaneously deliver the anticancer drug paclitaxel and photothermal agent palladium phthalocyanine to tumors through enhanced permeation and the retention effect. A combinational CHT/PTT therapy on mice bearing aggressive tumor grafts is conducted. The highly malignant tumor model, which recurs after sole treatment of PTT, can be eradicated by the combined CHT/PTT treatment. In addition, most of the off-targeted HPSN nanocarriers can be excreted through a hepatobiliary pathway in about 10 d. Serology results show that the fast-clearable HPSN can significantly reduce the side effect of the loaded paclitaxel drug. The present work provides an alternative approach for combinational cancer treatment with high therapeutic efficiency.

Resonance energy transfer (RET) describes the process that energy is transferred from an excited donor to an acceptor molecule, leading to a reduction in the fluorescence emission intensity of the donor and an increase in that of the acceptor. By this technique, measurements with the good sensitivity can be made about distance within 1 to 10 nm under physiological conditions. For this reason, the RET technique has been widely used in polymer science, biochemistry, and structural biology. Recently, a number of RET systems incorporated with nanoparticles, such as quantum dots, gold nanoparticles, and upconversion nanoparticles, have been developed. These nanocrystals retain their optical superiority and can act as either a donor or a quencher, thereby enhancing the performance of RET systems and providing more opportunities in excitation wavelength selection. Notably, lanthanide-doped upconversion nanophosphors (UCNPs) have attracted considerable attention due to their inherent advantages of large anti-Stoke shifts, long luminescence lifetimes, and absence of autofluorescence under low energy near-infrared (NIR) light excitation. These nanoparticles are promising for the biodetection of various types of analytes. Undoubtedly, the developments of those applications usually rely on resonance energy transfer, which could be regarded as a flexible technology to mediate energy transfer from upconversion phosphor to acceptor for the design of luminescent functional nanoplatforms. Currently, researchers have developed many RET-based upconversion nanosystems (RET-UCNP) that respond to specific changes in the biological environments. Specifically, small organic molecules, biological molecules, metal-organic complexes, or inorganic nanoparticles were carefully selected and bound to the surface of upconversion nanoparticles for the preparation of RET-UCNP nanosystems. Benefiting from the advantage and versatility offered by this technology, the research of RET-based upconversion nanomaterials should have significant implications for advanced biomedical applications. It should be noted that energy transfer in a UCNP based nanosystem is most often related to resonance energy transfer but that reabsorption (and maybe other energy transfer processes) may also play an important role and that more studies regarding the fundamental aspects for energy transfer with UCNPs is necessary. In this Account, we present an overview of recent advances in RET-based upconversion nanocomposites for biodetection with a particular focus on our own work. We have designed a series of upconversion nanoplatforms with remarkably high versatility for different applications. The experience gained from our strategic design and experimental investigations will allow for the construction of next-generation luminescent nanoplatform with marked improvements in their performance. The key aspects of this Account include fundamental principles, design and preparation strategies, biodetection in vitro and in vivo, future opportunities, and challenges of RET-UCNP nanosystems.

A red-light-controllable soft actuator has been achieved, driven by low-power excited triplet-triplet annihilation-based upconversion luminescence (TTA-UCL). First, a red-to-blue TTA-based upconversion system with a high absolute quantum yield of 9.3 ± 0.5% was prepared by utilizing platinum(II) tetraphenyltetrabenzoporphyrin (PtTPBP) as the sensitizer and 9,10-bis(diphenylphosphoryl)anthracene (BDPPA) as the annihilator. In order to be employed as a highly effective phototrigger of photodeformable cross-linked liquid-crystal polymers (CLCPs), the PtTPBPBDPPA system was incorporated into a rubbery polyurethane film and then assembled with an azotolane-containing CLCP film. The generating assembly film bent toward the light source when irradiated with a 635 nm laser at low power density of 200 mW cm(-2) because the TTA-UCL was effectively utilized by the azotolane moieties in the CLCP film, inducing their trans-cis photoisomerization and an alignment change of the mesogens via an emission-reabsorption process. It is the first example of a soft actuator in which the TTA-UCL is trapped and utilized to create photomechanical effect. Such advantages of using this novel red-light-controllable soft actuator in potential biological applications have also been demonstrated as negligible thermal effect and its excellent penetration ability into tissues. This work not only provides a novel photomanipulated soft actuation material system based on the TTA-UCL technology but also introduces a new technological application of the TTA-based upconversion system in photonic devices.

A general strategy for constructing high-effective upconversion nanocapsules based on triplet-triplet annihilation (TTA) was developed by loading both sensitizer and annihilator into BSA-dextran stabilized oil droplets. This strategy can maintain high translational mobility of the chromophores, avoid luminescence quenching of chromophore by aggregation, and decrease the O2-induced quenching of TTA-based upconversion emission. Pt(II)-tetraphenyl-tetrabenzoporphyrin (PtTPBP) and BODIPY dyes (BDP-G and BDP-Y with the maximal fluorescence emission at 528 and 546 nm, respectively) were chosen as sensitizer/annihilator couples to fabricate green and yellow upconversion luminescent emissive nanocapsules, named UCNC-G and UCNC-Y, respectively. In water under the atmospheric environment, interestingly, UCNC-G and UCNC-Y exhibit intense upconversion luminescence (UCL) emission (λex = 635 nm) with the quantum efficiencies (ΦUCL) of 1.7% and 4.8%, respectively, whereas very weak UCL emission (ΦUCL0.1%) was observed for the corresponding previous reported SiO2-coating nanosystems because of aggregation-induced fluorescence quenching of annihilators. Furthermore, application of theses upconversion nanocapsules for high-contrast UCL bioimaging in vivo of living mice without removing the skin was demonstrated under 635-nm excitation with low power density of 12.5 mW cm(-2).

We demonstrate molecular upconversion probe, NRh-1, which shows excellent photostability, high quantum yield up to 1.8%, and rapid excretion capability. The NIR-to-NIR upconversion technique offers remarkably improved signal-to-noise ratios and substantially higher tissue penetration depth.

Photothermal therapy (PTT) at present, following the temperature definition for conventional thermal therapy, usually keeps the temperature of lesions at 42–45 °C or even higher. Such high temperature kills cancer cells but also increases the damage of normal tissues near lesions through heat conduction and thus brings about more side effects and inhibits therapeutic accuracy. Here we use temperature-feedback upconversion nanoparticle combined with photothermal material for real-time monitoring of microscopic temperature in PTT. We observe that microscopic temperature of photothermal material upon illumination is high enough to kill cancer cells when the temperature of lesions is still low enough to prevent damage to normal tissue. On the basis of the above phenomenon, we further realize high spatial resolution photothermal ablation of labelled tumour with minimal damage to normal tissues in vivo. Our work points to a method for investigating photothermal properties at nanoscale, and for the development of new generation of PTT strategy., In photothermal therapy for cancer treatment, hyperthermic effects can damage healthy tissues and inhibit therapeutic efficacy. Here, the authors use core-shell lanthanide-based nanoparticles to monitor microscopic temperatures and to ablate cancer tissue at low temperatures.

Two kinds of composite films were obtained by incorporating upconversion nanophosphors into monodomain and polydomain crosslinked liquid crystalline polymer films containing azotolane moieties. When exposure to continuous-wave near-infrared light at 980 nm, the monodomain composite film generated fast bending along the rubbing direction of the polyimide alignment layers, whereas the bending direction of the polydomain composite film was random. The anisotropic effect of the azotolane mesogens on the deformation and the measurement of thermal effect indicate that the bending is caused by the means of photochemistry rather than the thermal effect of NIR light; that is, the upconversion luminescence of the nanophosphors leads to trans−cis photoisomerization of the azotolane units and the alignment change of the mesogens.

Rare-earth upconversion nanophosphors (UCNPs), when excited by continuous-wave near-infrared light, exhibit a unique narrow photoluminescence with higher energy. Such special upconversion luminescence makes UCNPs promising as bioimaging probes with attractive features, such as no auto-fluorescence from biological samples and a large penetration depth. As a result, UCNPs have emerged as novel imaging agents for small animals. In this critical review, recent reports regarding the synthesis of water-soluble UCNPs and their surface modification and bioconjugation chemistry are summarized. The applications of UCNPs for small-animal imaging, including tumor-targeted imaging, lymphatic imaging, vascular imaging and cell tracking are reviewed in detail. The exploration of UCNPs as multifunctional nanoscale carriers for integrated imaging and therapy is also presented. The biodistribution and toxicology of UCNPs are further described. Finally, we discuss the challenges and opportunities in the development of UCNP-based nanoplatforms for small-animal imaging (276 references).

By thermal decomposition in the presence only of oleylamine, sub-10 nm hexagonal NaLuF(4)-based nanocrystals codoped with Gd(3+), Yb(3+), and Er(3+) (or Tm(3+)) have been successfully synthesized. Sub-10 nm β-NaLuF(4): 24 mol % Gd(3+), 20 mol % Yb(3+), 1 mol % Tm(3+) nanocrystals display bright upconversion luminescence (UCL) with a quantum yield of 0.47 ± 0.06% under continuous-wave excitation at 980 nm. Furthermore, through the use of β-NaLuF(4):Gd(3+),Yb(3+),Tm(3+) nanocrystals as a luminescent label, the detection limit of50 nanocrystal-labeled cells was achieved for whole-body photoluminescent imaging of a small animal (mouse), and high-contrast UCL imaging of a whole-body black mouse with a penetration depth of ~2 cm was achieved.

Chromophoric iridium(III) complex-coated NaYF(4): 20%Yb, 1.6%Er, 0.4%Tm nanocrystals are demonstrated as a ratiometric upconversion luminescence (UCL) probe for highly selective detection of cyanide anion and bioimaging of CN(-) in living cells through inhibition of the energy transfer from the UCL of the nanocrystals to the absorbance of the chromophoric complex. The UCL probe provides a very low detection limit of 0.18 μM CN(-) in the aqueous solution.

Self-assembly of cadmium ions and the rigid bridging ligand 4,4′-methylenebis(3-hydroxy-2-naphthoic acid) (pamoic acid, H4PA) leads to a one-dimensional metal-organic framework with open cube-like M2(H2PA)2 cages within its backbone, and exhibiting interesting yellow fluorescence.

A new kind of 1-phenyl-3-methyl-4-octadecyl-5-pyrazolone (PMOP)-capped ZnO nanoparticle has been synthesized and characterized with UV–VIS, IR and fluorescent spectra. The material was used as a framework to form a quasi-solid-state electrolyte and employed in dye-sensitized solar cell (DSSC). Since the long alkyl-chain of PMOP interacts with liquid solvent, the quasi-solid-state DSSC with PMOP-capped nanoparticles shows higher stability in comparison with that of the liquid device and gives a comparable overall efficiency of 6.8% under AM 1.5 illumination.

Near-IR (NIR) emission can offer distinct advantages for both in vitro and in vivo biological applications. Two NIR fluorescent turn-on sensors N,N'-di-n-butyl-2-(N-{2-[bis(pyridin-2-ylmethyl)amino]ethyl})-6-(N-piperidinyl)naphthalene-1,4,5,8-tetracarboxylic acid bisimide and N,N'-di- n-butyl-2-[N,N,N'-tri(pyridin-2-ylmethyl)amino]ethyl-6-(N-piperidinyl)naphthalene-1,4,5,8-tetracarboxylic acid bisimide (PND and PNT) for Zn(2+) based on naphthalenediimide fluorophore are reported. Our strategy was to choose core-substituted naphthalenediimide (NDI) as a novel NIR fluorophore and N,N-di(pyridin-2-ylmethyl)ethane-1,2-diamine (DPEA) or N,N,N'-tri(pyridin-2-ylmethyl)ethane-1,2-diamine (TPEA) as the receptor, respectively, so as to improve the selectivity to Zn(2+). In the case of PND, the negligible shift in absorption and emission spectra is strongly suggestive that the secondary nitrogen atom (directly connected to the NDI moiety, N(1)) is little disturbed with Zn(2+). The fluorescence enhancement of PND with Zn(2+) titration is dominated with a typical photoinduced electron-transfer (PET) process. In contrast, the N(1) atom for PNT can participate in the coordination of Zn(2+) ion, diminishing the electron delocalization of the NDI moiety and resulting in intramolecular charge-transfer (ICT) disturbance. For PNT, the distinct blueshift in both absorbance and fluorescence is indicative of a combination of PET and ICT processes, which unexpectedly decreases the sensitivity to Zn(2+). Due to the differential binding mode caused by the ligand effect, PND shows excellent selectivity to Zn(2+) over other metal ions, with a larger fluorescent enhancement centered at 650 nm. Also both PND and PNT were successfully used to image intracellular Zn(2+) ions in the living KB cells.

Lanthanide-doped up-conversion nanoparticles (UCNPs) provide a remote temperature sensing approach to monitoring biological microenvironments. In this research, the UCNPs of NaYF4:Yb3+, Er3+@NaYF4:Yb3+, Nd3+ with hexagonal (β)-phase were synthesized and applied in cell temperature sensing as well as imaging after surface modification with meso-2, 3-dimercaptosuccinic acid. In the core–shell UCNPs, Yb3+ ions were introduced as energy transfer media between sensitizers of Nd3+ and activators of Er3+ to improve Er3+emission and prevent their quenching behavior due to multiple energy levels of Nd3+. Under the excitations of 808 nm and 980 nm lasers, the NaYF4:Yb3+, Er3+@NaYF4:Yb3+, Nd3+ nanoparticles exhibited an efficient green band with two emission peaks at 525 nm and 545 nm, respectively, which originated from the transitions of 2H11/2 → 4I15/2 and 4S3/2 → 4I15/2 for Er3+ ions. We demonstrate that an occurrence of good logarithmic linearity exists between the intensity ratio of these two emission peaks and the reciprocal of the inside or outside temperature of NIH-3T3 cells. A better thermal stability is proved through temperature-dependent spectra with a heating–cooling cycle. The obtained viability of NIH-3T3 cells is greater than 90% after incubations of about 12 and 24 (h), and they possess a lower cytotoxicity of UCNPs. This work provides a method for monitoring the cell temperature and its living state from multiple dimensions including temperature response, cell images and visual up-conversion fluorescent color.

A family of asymmetric cholesterol-based fluorescent organogelators containing naphthalimide, connected by two acylamines and different alkyl-chain spacers, have been designed and prepared. These compounds can gelate a variety of organic solvents with both ultrasound stimuli and general sol-gel processes. The self-assembly and gelling properties of the compounds depend on the length of the alkyl chains and can be controlled by ultrasound stimuli and renewed by a thermodynamic process. The morphologies and surface wetabilities of the xerogels prepared from these gelators are strongly affected by environmental stimuli. The mechanism of the process was investigated by confocal laser scanning microscopy, transmission or scanning electron microscopy, wide-angle X-ray scattering analysis, and rheological experiments. The studies reveal that the cooperation and relative competition of multiple intermolecular interactions, influenced by the sonication or thermal stimulus, are the main contributors for the aggregation or nucleation processes; this results in the macrodifferences in morphology and surface properties. These results provide a deeper understanding of the intermediate transition state of the gel during use of an ultrasound stimulus.