ABSTRACT
Trace NO2 detection is essential for the production and life, where the sensing strategy is appropriate for rapid detection but lacks molecular specificity. This investigation proposes a sensing mechanism dominated by surface-scattering to achieve the molecularly-specific detection. Two-dimensional Bi2O2Se is firstly fabricated into a Schottky-junction-based gas-sensor. Applied with an alternating excitation, the sensor simultaneously outputs multiple response signals (i.e., resistance, reactance, and the impedance angle). Their response times are shorter than 200 s at room temperature. In NO2 sensing, these responses present the detection limit in ppt range and the sensitivity is up to 16.8 %·ppb-1. This NO2 sensitivity presents orders of magnitude higher than those of the common gases within the exhaled breath. The impedance angle is involved in the principle component analysis together with the other two sensing signals. Twelve kinds of typical gases containing NO2 are acquired with molecular characteristics. The change in dipole moment of the target molecule adsorbed is demonstrated to correlate with the impedance angle via surface scattering. The proposed mechanism is confirmed to output ultra-sensitive sensing responses with the molecular characteristic.
ABSTRACT
The importance of halogen bonds (XBs) in the regulation of material properties through a variation in the electrostatic potential of the halogen atom is not attracted much attention. Herein, this study utilizes in situ single crystal X-ray diffraction and synchrotron-based X-ray techniques to investigate the cooling-triggered irreversible single-crystal-to-single-crystal transformation of the DMF solvated iodo-substituted squaraine dye (SQD-I). Transformation is observed to be mediated by solvent-involved XB formation and strengthening of electrostatic interaction between adjacent SQD-I molecules. By immersing a DMF solvate in acetonitrile a solvent exchange without loss of long-range ordering is observed. This is attributed to conservation of the molecular charge distribution of SQD-I molecules during the process. The different solvates can be used in combination for temperature-dependent image encryption. This work emphasizes the changes caused by XB formation to the electrostatic potentials of halogen containing molecules and their influence on material properties and presents the potential utility of XBs in the design of soft-porous crystals and luminescent materials.
ABSTRACT
Nonalcoholic steatohepatitis (NASH) is the critical stage in the development of nonalcoholic fatty liver disease (NAFLD) from simple and reversible steatosis to irreversible cirrhosis and even hepatocellular carcinoma (HCC). Thus, the diagnosis of NASH is important for preventing the progress of NAFLD into a fatal condition. The oxidative enzyme myeloperoxidase (MPO), which is mostly produced by polymorphonuclear neutrophil granulocytes (NEU), has been identified as a key player in lipid peroxidation in inflamed tissues. Considering that the expression of MPO was much higher in NASH than in the nonalcoholic fatty liver (NAFL) with steatosis, we designed a nanoparticle platform based on ultrasmall iron oxide (USIO) nanoparticles to realize MPO-sensitive NASH diagnosis. After modification of USIO nanoparticles with amphiphilic poly(ethylene glycol) (PEG) and conjugation with 5-hydroxytryptamine (5HT), a physiological substrate for MPO, the final nanocomposite (USIO-DA-PEG-5HT) revealed MPO-mediated aggregation at the inflammatory site of NASH. Meanwhile, the intrinsic T1-weighted magnetic resonance (MR) signal of dispersed USIO-DA-PEG-5HT nanoparticles diminishes, while the T2-weighted MR signal is amplified owing to the aggregation effect. These USIO-DA-PEG-5HT nanoprobes offer great potential for improving NASH MR imaging diagnostic accuracy and sensitivity compared to existing molecular MR contrast agents with a single imaging modality.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/metabolism , Liver/metabolism , Carcinoma, Hepatocellular/pathology , Peroxidase/metabolism , Liver Neoplasms/pathology , Magnetic Resonance Imaging/methodsABSTRACT
Developing a ferroelectric tunnel junction with a robust polarization reversal is essential for errorless data storage, but it remains challenging since the second-order phase transition dominates the reversal and introduces intermediate states. This investigation has proposed a charge-gradient-induced ferroelectricity, which is featured with the first-order phase transition. As an order parameter, a charge-gradient-induced polarization is achieved by modulation of stoichiometric oxygen along the Bi2O2Se/Bi2Se3O9 bilayer during pulsed laser deposition. At room temperature, this polarity points out-of-plane and shows an abrupt reversal in the ferroelectric hysteresis loop. The coercive field only increases by 0.04 V/nm after 300 reversals. Fabricated into the ferroelectric tunnel junction, the bilayer ferroelectric exhibits a comparable electroresistance of 100. The ON/OFF state can be switched repeatedly or after a 360 s retention. Characterizations of scanning capacitance microscopy and the current-voltage relation demonstrate that the ON/OFF switching is based on an injection exchange between the tunnelling and the thermionic emission.
ABSTRACT
π-Molecules play important roles in many applications such as organic light-emitting devices, photocatalysis, photovoltaics, biosensors, and medicine. Very often, π-conjugated molecules with high utilization of excited states in the solid state are of great research interest. However, owing to the gap between molecular structure and effective molecular packing, there are very few designs toward π molecules with very high exciton utilization in the solid state. Herein, we report a new π skeleton, folded π, to achieve high exciton utilization in the solid state. Based on a "folded π" formula, 12 compounds with two or three folding π planes were designed and synthesized. We found that folded π molecules tend to form well-aligned 1D molecular columns of patterns ("box", "braid", or "stair") with high packing energy, which is mainly contributed by numerous weak π interactions. As a result of effective suppression of molecular motion, all the compounds show very high exciton utilization in solids.
Subject(s)
Molecular Structure , Physical PhenomenaABSTRACT
Three conjugated polymers that have the same donor-acceptor structure but totally different architectures are designed to show both Type-I and Type-II photosensitization abilities simultaneously, among which the hyperbranched polymer shows the best performance in both in vitro and in vivo experiments, superior to even the commonly used clinical photosensitizer of hemoporfin.
Subject(s)
Photochemotherapy , Photosensitizing Agents , Photosensitizing Agents/chemistry , Polymerization , Polymers/chemistryABSTRACT
Porous organic cages (POCs) have many advantages, including superior microenvironments, good monodispersity, and shape homogeneity, excellent molecular solubility, high chemical stability, and intriguing host-guest chemistry. These properties enable POCs to overcome the limitations of extended porous networks such as metal-organic frameworks (MOFs) and covalent organic frameworks (COFs). However, the applications of POCs in bioimaging remain limited due to the problems associated with their rigid and hydrophobic structures, thus leading to strong aggregation-caused quenching (ACQ) in aqueous biological media. To address this challenge, we report the preparation of aggregation-induced emission (AIE)-active POCs capable of stimuli responsiveness for enhanced bioimaging. We rationally design a hydrophilic, structurally flexible tetraphenylethylene (TPE)-based POC that is almost entirely soluble in aqueous solutions. This POC's conformationally flexible superstructure allows the dynamic rotation of the TPE-based phenyl rings, thus endowing impressive AIE characteristics for responses to environmental changes such as temperature and viscosity. We employ these notable features in the bioimaging of living cells and obtain good performance, demonstrating that the present AIE-active POCs are suitable candidates for further biological applications.
Subject(s)
Metal-Organic Frameworks , Diagnostic Imaging , PorosityABSTRACT
The pursuing of photosensitizers (PSs) with efficient reactive oxygen species (ROS) especially type I ROS generation in aggregate is always in high demand for photodynamic therapy (PDT) and photoimmunotherapy but remains to be a big challenge. Herein, we report a cationization molecular engineering strategy to boost both singlet oxygen and radical generation for PDT. Cationization could convert the neutral donor-acceptor (D-A) typed molecules with the dicyanoisophorone-triphenylamine core (DTPAN, DTPAPy) to their A-D-A' typed cationic counterparts (DTPANPF6 and DTPAPyPF6). Our experiment and simulation results reveal that such cationization could enhance the aggregation-induced emission (AIE) feature, promote the intersystem crossing (ISC) processes, and increase the charge transfer and separation ability, all of which work collaboratively to promote the efficient generation of ROS especially hydroxyl and superoxide radicals in aggregates. Moreover, these cationic AIE PSs also possess specific cancer cell mitochondrial targeting capability, which could further promote the PDT efficacy both in vitro and in vivo. Therefore, we expect this delicate molecular design represents an attractive paradigm to guide the design of type I AIE PSs for the further development of PDT.
Subject(s)
Neoplasms , Photochemotherapy , Humans , Neoplasms/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Reactive Oxygen Species/metabolism , Singlet Oxygen/metabolismABSTRACT
For practical applications, molecules often exist in an aggregate state. Therefore, it is of great value if one can predict the performance of molecules when forming aggregates, for example, aggregation-induced emission (AIE) or aggregation-caused quenching (ACQ). Herein, a database containing AIE/ACQ molecules reported in the literature is first established. Through training, these machine learning (ML) models can build up the structure-property relationship and thus implement fast prediction of AIE/ACQ properties. To this end, a multi-modal approach is proposed, multiple prediction methods are compared and designed, and thus an ensemble strategy is developed. First, multiple molecular descriptors are considered at the same time, major features are extracted by dimensionality reduction, and multi-modal features are synthesized. Then, several state-of-the-art methods are designed and compared to analyze the advantages of the different methods. Finally, the ensemble strategy combines the advantages of the multiple methods to obtain the final prediction result. The reliability of this approach in an unknown molecular space is further verified by three newly designed molecules. Reasonable consistency between model predictions and experimental outcomes is obtained. The result indicates that ML can be a powerful tool to predict molecular properties in the aggregated state, thus accelerating the development of solid-state optical materials.
ABSTRACT
Artificial intelligence (AI) based self-learning or self-improving material discovery system will enable next-generation material discovery. Herein, we demonstrate how to combine accurate prediction of material performance via first-principle calculations and Bayesian optimization-based active learning to realize a self-improving discovery system for high-performance photosensitizers (PSs). Through self-improving cycles, such a system can improve the model prediction accuracy (best mean absolute error of 0.090 eV for singlet-triplet spitting) and high-performance PS search ability, realizing efficient discovery of PSs. From a molecular space with more than 7 million molecules, 5357 potential high-performance PSs were discovered. Four PSs were further synthesized to show performance comparable with or superior to commercial ones. This work highlights the potential of active learning in first-principle-based materials design, and the discovered structures could boost the development of photosensitization related applications.
ABSTRACT
Infections caused by Gram-positive bacteria, especially those able to invade and survive in host cells, threaten human health severely. It is therefore highly desirable to develop therapeutics that can selectively target and kill intracellular Gram-positive pathogens with minimal toxicity to host cells. Herein, it is described that the aggregation-induced emission luminogen (AIEgen) TPEPy-Et, containing a positively charged pyridinium group and a hydrophobic tetraphenylethylene fragment, is effective for Gram-positive bacteria detection and elimination. The fluorescence of TPEPy-Et is greatly enhanced after incubation with Gram-positive bacteria, which can be used to detect and trace the bacteria in cells. TPEPy-Et also shows excellent killing effects against both extracellular and intracellular Gram-positive bacteria through a membrane depolarization mechanism. The luminescent antibacterial agent TPEPy-Et is thus promising for diagnosis and therapy against intracellular bacterial infection.
Subject(s)
Anti-Bacterial Agents , Gram-Positive Bacteria , Anti-Bacterial Agents/pharmacology , Bacteria , Fluorescence , Gram-Negative Bacteria , HumansABSTRACT
Photodynamic therapy (PDT) is a promising noninvasive treatment option for patients suffering from superficial tumors, such as oral cancer. However, for photosensitizers (PSs), it remains a grand challenge to simultaneously excel in all the key performance indicators including effective singlet oxygen (1O2) generation under clinical laser, specific targeting function and stable far-red (FR)/near-infrared (NIR) emission with low dark toxicity. In addition, traditional PS nanoparticles (NPs) for clinical use suffer from quenched fluorescence and reduced 1O2 production caused by molecular aggregation. To address these issues, AIEPS5 with aggregation-induced FR/NIR emission and effective 1O2 generation under 532 nm laser irradiation is designed by precise optimization of the chemical structure. By attaching a polyethylene glycol (PEG) chain onto AIEPS5, the yielded amphiphilic AIEPS5-PEG2000 can spontaneously self-assemble into water dispersible NPs, which are further endowed with targeted delivery function via the decoration of anti-Her-2 nanobody (NB). The bespoke AIEPS5-NPs-NB exhibit effective 1O2 generation capability, bright FR/NIR emission centered at 680 nm, and negligible dark toxicity, which outperform Heimbofen, a clinically approved PS in PDT using a patient-derived tumor xenograft model.
Subject(s)
Mouth Neoplasms , Nanoparticles , Photochemotherapy , Heterografts , Humans , Mouth Neoplasms/drug therapy , Photosensitizing AgentsABSTRACT
Ferroptosis regulates cell death through reactive oxygen species (ROS)-associated lipid peroxide accumulation, which is expected to affect the structure and polarity of lipid droplets (LDs), but with no clear evidence. Herein, we report the first example of an LD/nucleus dual-targeted ratiometric fluorescent probe, CQPP, for monitoring polarity changes in the cellular microenvironment. Due to the donor-acceptor structure of CQPP, it offers ratiometric fluorescence emission and fluorescence lifetime signals that reflect polarity variations. Using nucleus imaging as a reference, CQPP was applied to report the increase in LD polarity and the homogenization of polarity between LDs and cytoplasm in the ferroptosis model. This LD/nucleus dual-targeted fluorescent probe shows the great potential of using fluorescence imaging to study ferroptosis and ferroptosis-related diseases.
Subject(s)
Cell Nucleus/metabolism , Fluorescent Dyes/chemistry , Lipid Droplets/metabolism , Ferroptosis , Fluorescent Dyes/chemical synthesis , Humans , Lipid Droplets/chemistry , Molecular Structure , Reactive Oxygen Species/metabolismABSTRACT
Maximization of phototoxic damage on tumor with minimized side effect on normal tissue is essential for effective anticancer photodynamic therapy (PDT). This requires highly cancer-cell-specific or even cancer-cell-organelle-specific synthesis or delivery of efficient photosensitizers (PSs) in vitro and in vivo, which is difficult to achieve. Herein, we report a strategy of cancer-cell-activated PS synthesis, by which an efficient mitochondria-targeting photosensitizer with aggregation-induced-emission (AIE) feature can be selectively synthesized as an efficient image-guided PDT agent inside cancer cells. MOF-199, a CuII -based metal-organic framework, was selected as an inert carrier to load the PS precursors for efficient delivery and served as a CuI catalyst source for in situ click reaction to form PSs exclusively in cancer cells. The in situ synthesized PS showed mitochondria-targeting capability, allowing potent cancer-cell-specific ablation under light irradiation. The high specificity of PSs produced in cancer cells also makes it safer post-treatment.
Subject(s)
Antineoplastic Agents/pharmacology , Coordination Complexes/pharmacology , Copper/pharmacology , Mitochondria/drug effects , Neoplasms/drug therapy , Photochemotherapy , Photosensitizing Agents/pharmacology , 3T3 Cells , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Copper/chemistry , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Mice , Neoplasms/metabolism , Neoplasms/pathology , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistryABSTRACT
Isomerization is an essential chemical process that often evokes dramatic change of chemical, physical, or biological properties. For a long time, isomerization has been known as a transformation that is induced by certain external energy such as light, heat, or mechanical force. Herein, a new isomerization phenomenon is described, which does not require external energy but simply occurs during molecular packing. The proposed isomerization is demonstrated by a series of symmetric donor-acceptor-donor (D-A-D) molecules, the donor of which may adopt two different stereoisomeric forms. Based on the evidence of the asymmetric isomers in crystals, the occurrence of isomerization during molecular packing is proved. Moreover, the unique asymmetric geometry in the solid state favors the restriction of intramolecular motion, resulting in highly efficient organic solids with quantum yields approaching unity.
ABSTRACT
Tumor accumulation and intratumoral singlet oxygen (1O2) generation efficiency of photosensitizers (PSs) are two essential factors that determine their photodynamic therapy (PDT) efficacies. How to maximize the PS performance at the tumor site is of great research interest. Herein, we report a metal-organic framework (ZIF-8, ZIF = zeolitic imidazolate framework) assisted in vivo self-assembly nanoplatform, ZIF-8-PMMA-S-S-mPEG, as an effective tool for organic PS payloads to achieve efficient PDT. Using an organic PS with aggregation-induced emission as an example, under intratumoral bioreduction, PS-loaded ZIF-8-PMMA-S-S-mPEG (PS@ZIF-8-PMMA-S-S-mPEG) was self-assembled into large ordered hydrophobic clusters, which greatly enhance tumor retention and accumulation of the PS. Moreover, hydrophobic ZIF-8 assemblies greatly isolate the loaded PSs from water and improve O2 transport for the PSs to effectively produce 1O2 inside tumors under light irradiation. The organic PS is therefore endowed with optimal tumor accumulation and intratumoral 1O2 production, demonstrating the effectiveness of the developed self-assembly strategy in PDT application.
Subject(s)
Metal-Organic Frameworks , Neoplasms , Photochemotherapy , Humans , Neoplasms/drug therapy , Photosensitizing Agents , Singlet OxygenABSTRACT
Reactive oxygen species (ROS) are essential for the regulation of antitumor immune responses, where they could induce immunogenic cell death, promote antigen presentation, and activate immune cells. Here, we report the development of near-infrared (NIR)-driven immunostimulants, based on coupling upconversion nanoparticles with aggregation-induced emission luminogens (AIEgens), to integrate the immunological effects of ROS for enhanced adaptive antitumor immune responses. Intratumorally injected AIEgen-upconversion nanoparticles produce high-dose ROS under high-power NIR irradiation, which induces immunogenic cell death and antigen release. These nanoparticles can also capture the released antigens and deliver them to lymph nodes. Upon subsequent low-power NIR treatment of lymph nodes, low-dose ROS are generated to further trigger efficient T cell immune responses through activation of dendritic cells, preventing both local tumor recurrence and distant tumor growth. The utility of dual-mode pumping power on AIEgen-coupled upconversion nanoparticles offers a powerful and controllable platform to activate adaptive immune systems for tumor immunotherapy.
Subject(s)
Nanoparticles , Neoplasms , Cell Line, Tumor , Humans , Immunotherapy , Nanoparticles/therapeutic use , Neoplasms/drug therapy , Reactive Oxygen Species/metabolismABSTRACT
In order to promote the development of photodynamic therapy (PDT), undesired side effects like low tumor specificity and the "always-on" phenomenon should be avoided. An effective solution is to construct an adaptive photosensitizer that can be activated to generate reactive oxygen species (ROS) in the tumor microenvironment. Herein, we design and synthesize a supramolecular switch based on a host-guest complex containing a water-soluble pillar[5]arene (WP5) and an AIEgen photosensitizer (G). The formation of the host-guest complex WP5âG quenches the fluorescence and inhibits ROS generation of G. Benefitting from the pH-responsiveness of WP5, the binding site between G and WP5 changes in an acidic environment through a shuttle movement. Consequently, fluorescence and ROS generation of the host-guest complex can be switched on at pHâ 5.0. This work offers a new paradigm for the construction of adaptive photosensitizers by using a supramolecular method.
Subject(s)
Calixarenes/chemistry , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/pharmacology , 3T3 Cells , Acids , Animals , Drug Design , Fluorescence , HeLa Cells , Humans , Hydrogen-Ion Concentration , Mice , Models, Molecular , Photochemotherapy , Reactive Oxygen Species/chemistryABSTRACT
Precise design of fluorescent molecules with desired properties has enabled the rapid development of many research fields. Among the different types of optically active materials, luminogens with aggregation-induced emission (AIEgens) have attracted significant interest over the past two decades. The negligible luminescence of AIEgens as a molecular species and high brightness in aggregate states distinguish them from conventional fluorescent dyes, which has galvanized efforts to bring AIEgens to a wide array of multidisciplinary applications. Herein, the useful principles and emerging structure-property relationships for precise molecular design toward AIEgens with desirable properties using concrete examples are revealed. The cutting-edge applications of AIEgens and their excellent performance in enabling new research directions in biomedical theranostics, optoelectronic devices, stimuli-responsive smart materials, and visualization of physical processes are also highlighted.
ABSTRACT
Diagnostics of cerebrovascular structures and microscopic tumors with intact blood-brain barrier (BBB) significantly contributes to timely treatment of patients bearing neurological diseases. Dual NIR-II fluorescence and photoacoustic imaging (PAI) is expected to offer powerful strength, including good spatiotemporal resolution, deep penetration, and large signal-to-background ratio (SBR) for precise brain diagnostics. Herein, biocompatible and photostable conjugated polymer nanoparticles (CP NPs) are reported for dual-modality brain imaging in the NIR-II window. Uniform CP NPs with a size of 50 nm are fabricated from microfluidics devices, which show an emission peak at 1156 nm with a large absorptivity of 35.2 L g-1 cm-1 at 1000 nm. The NIR-II fluorescence imaging resolves hemodynamics and cerebral vasculatures with a spatial resolution of 23 µm at a depth of 600 µm. The NIR-II PAI enables successful noninvasive mapping of deep microscopic brain tumors (<2 mm at a depth of 2.4 mm beneath dense skull and scalp) with an SBR of 7.2 after focused ultrasound-induced BBB opening. This study demonstrates that CP NPs are promising contrast agents for brain diagnostics.