Green, General and Low-cost Synthesis of Porous Organic Polymers in Sub-kilogram Scale for Catalysis and CO2 Capture.

Porous organic polymers (POPs) with high porosity and tunable functionalities have been widely studied for use in gas separation, catalysis, energy conversion and energy storage. However, the high cost of organic monomers, and the use of toxic solvents and high temperatures during synthesis pose obstacles for large-scale production. Herein, we report the synthesis of imine and aminal-linked POPs using inexpensive diamine and dialdehyde monomers in green solvents. Theoretical calculations and control experiments show that using meta-diamines is crucial for forming aminal linkages and branching porous networks from [2+2] polycondensation reactions. The method demonstrates good generality in that 6 POPs were successfully synthesized from different monomers. Additionally, we scaled up the synthesis in ethanol at room temperature, resulting in the production of POPs in sub-kilogram quantities at a relatively low cost. Proof-of-concept studies demonstrate that the POPs can be used as high-performance sorbents for CO2 separation and as porous substrates for efficient heterogeneous catalysis. This method provides an environmentally friendly and cost-effective approach for large-scale synthesis of various POPs.

Programmable Assembly of Multivalent DNA-Protein Superstructures for Tumor Imaging and Targeted Therapy.

Programmable DNA materials hold great potential in biochemical and biomedical researches, yet the complicated synthesis, and the low stability and targeting efficacy in complex biological milieu limit their clinical translations. Here we show a one-pot assembly of DNA-protein superstructures as drug vehicles with specifically high affinity and stability for targeted therapy. This is achieved by biomimetic assembly of programmable polymer DNA wire into densely packed DNA nanosphere with an alkaline protein, protamine. Multivalent DNA nanostructures encoded with different types and densities of aptamers exhibit high affinity to targeted cells through polyvalent interaction. Our results show high cancer cell selectivity, reduced side effect, excellent therapeutic efficacy, and sensitive tumor imaging in both subcutaneous and orthotopic non-small-cell lung cancer murine models. This biomimetic assembly approach provides practical DNA nanomaterials for further clinical trials and may advance oligonucleotide drug delivery.

A Cooperatively Activatable DNA Nanoprobe for Cancer Cell-Selective Imaging of ATP.

DNA-based nanoprobes have attracted extensive interest in the field of bioanalysis. Notably, engineered DNA nanoprobes that can respond to multiple pathological parameters are desirable to detect targets precisely. Here we design a split aptamer/DNAzyme (aptazyme)-based DNA probe for fluorescence detection of ATP and further develop a cooperatively activatable DNA nanoprobe for tumor-specific imaging of ATP in vivo. The DNA nanoprobes comprising split aptazyme-coated MnO2 nanovectors have high stability and are synergistically activated by multiple biomarkers, GSH and ATP. Upon stimuli by overexpressed GSH in tumor cells, this DNA nanoprobe can release the aptazyme and self-supply cofactor Mn2+ of the DNAzyme. Sequentially, intracellular ATP induces the proper folding of the split ATP aptamer and Mn2+-dependent DNAzyme, which activates the specific cleavage of substrate and generates the optical readout signal. This nanoprobe exhibits remarkable resistance to enzymatic degradation, satisfactory biosafety, identifies ATP specifically within cancer cells, and selectively lights up solid tumors. Our research provides a reliable method for ATP imaging in cancer cells and opens a new avenue for biochemical research and highly accurate disease diagnosis.

Visualization of Vaccine Dynamics with Quantum Dots for Immunotherapy.

The direct visualization of vaccine fate is important to investigate its immunoactivation process to elucidate the detailed molecular reaction process at single-molecular level. Yet, visualization of the spatiotemporal trafficking of vaccines remains poorly explored. Here, we show that quantum dot (QD) nanomaterials allow for monitoring vaccine dynamics and for amplified immune response. Synthetic QDs enable efficient conjugation of antigen and adjuvants to target tissues and cells, and non-invasive imaging the trafficking dynamics to lymph nodes and cellular compartments. The nanoparticle vaccine elicits potent immune responses and anti-tumor efficacy alone or in combination with programmed cell death protein 1 blockade. The synthetic QDs showed high fluorescence quantum yield and superior photostability, and the reliable and long-term spatiotemporal tracking of vaccine dynamics was realized for the first time by using the synthetic QDs, providing a powerful strategy for studying immune response and evaluating vaccine efficacy.

Biosynthesized Quantum Dot for Facile and Ultrasensitive Electrochemical and Electrochemiluminescence Immunoassay.

Nanomaterials are commonly utilized for amplified immunoassay of biomarkers. However, traditional nanomaterial-based immunoassay usually requires a time-consuming and labor-intensive nanoparticle modification and conjugation process, which impedes their practical applications. Here, a new immunoassay method based on biosynthesized nanomaterials is developed with versatile functions for facile and ultrasensitive detection of cancer biomarker. In this method, the utilized biosynthesized quantum dots (BQDs) allow convenient antibody conjugation and electrode modification, and demonstrate excellent electrochemical and electrochemiluminescent responses. The differential pulse voltammetric, faradaic impedance spectroscopy, and electrochemiluminescent measurements with the BQD-modified electrode show detection limits at picomolar levels as well as good specificity toward human prostate-specific antigen detection. The inherent recognization capability as well as the inherent electrochemical and electrochemiluminescence features thus enable BQDs as good candidates for facile immunosensors with high sensitivity. Such a biosynthesized nanomaterial-based approach opens up the possibility of using innovative designs for nanoparticle-based assays, and developing reliable and practical methods for early disease diagnosis.

A DNA-Mediated Chemically Induced Dimerization (D-CID) Nanodevice for Nongenetic Receptor Engineering To Control Cell Behavior.

Small-molecule regulation is a powerful switching tool to manipulate cell signal transduction for a desired function; however, most available methods usually require genetic engineering to endow cells with responsiveness to user-defined small molecules. Herein, we demonstrate a nongenetic approach for small-molecule-controlled receptor activation and consequent cell behavior manipulation that is based on DNA-mediated chemically induced dimerization (D-CID). D-CID uses a programmable chemical-responsive DNA nanodevice to trigger DNA strand displacement and induce the activation of c-Met, a tyrosine kinase receptor cognate for hepatocyte growth factor, through dimerization. Through the use of various functional nucleic acids, including aptamers and DNAzymes, as recognition modules, the versatility of D-CID in inducing c-Met signaling upon addition of various small-molecular or ionic cues, including ATP, histidine, and Zn2+ , is demonstrated. Moreover, owing its multi-input properties, D-CID can be used to manipulate the behaviors of multiple cell populations simultaneously in a selective and programmable fashion.

Risk Factors Associated With Postoperative Pulmonary Infection in Elderly Patients With Hip Fracture: A Longitudinal Study.

This study aimed to conduct a longitudinal study to explore the influencing factors of pulmonary infection in elderly patients with hip fracture after surgery, to provide evidence and reference for the early identification and nursing care of patients at high risk of postoperative pulmonary infection.A secondary analysis was conducted of electronic medical record data from elderly patients with hip fractures treated in a tertiary hospital from January 1, 2020 to June 30, 2021.A total of 526 patients were included. Age ≥70 years (odd ratio [OR] 2.042, 95% confidence interval [CI] [1.516-4.022]), history of smoking (OR 2.755, 95% CI [2.009-3.175]), time from fracture to operation ≥5 days (OR 3.117, 95% CI [1.925-3.911]), American Society of Anesthesiologists grade ≥II (OR 1.254, 95% CI [1.053-1.921]), chronic obstructive pulmonary disease (OR 2.832, 95% CI [1.775-3.808]), hypoproteinemia (OR 1.395, 95% CI [1.022-1.841]), red blood cell distribution width >15% (OR 3.142, 95% CI [2.104-4.172]), intensive care unit stay (OR 2.174, 95% CI [1.083-3.718]) and duration of mechanical ventilation ≥180 minutes (OR 3.117, 95% CI [2.199-4.807]) were the independent risk factors (all p < .05).Early nursing care should be taken for patients with risk factors to reduce the pulmonary infection.

Multiple Blockades of the HGF/Met Signaling Pathway for Metastasis Suppression Using Nanoinhibitors.

The hepatocyte growth factor (HGF)/HGF receptor (Met) signaling pathway serves as a potential target for preventing tumor metastasis yet poorly explored. Here, we developed a Met-targeted nanoinhibitor to efficiently suppress metastasis via a multiple blockading HGF/Met signaling pathway. A biocompatible nanovector comprising multiple type of inhibitors enables interrupting extracellular domain dimerization and intracellular domain phosphorylation simultaneously. Such a comprehensive blockade of signaling pathway restrains unregulated tumor cell migration, invasion, and proliferation and thus remarkably suppresses metastasis in an orthotopic breast tumor model. This method provides a safe and effective option for metastasis inhibition via modulation of the cell signaling pathway. To our best knowledge, the strategy of the multiple blockading signaling pathway has not been reported for preventing tumor metastasis.

A Mitochondrial Oxidative Stress Amplifier to Overcome Hypoxia Resistance for Enhanced Photodynamic Therapy.

Hypoxia-induced resistance to tumor treatment restricts further development of photodynamic therapy. Instead of simple reoxygenation to relieve hypoxia in traditional therapeutic approaches, a mitochondria-targeted reactive oxygen species (ROS) amplifier is constructed to reverse hypoxia resistance and enhance tumor sensitivity to hypoxia-resistant photodynamic therapy. Mesoporous silica nanoparticles are modified with triphenylphosphine to enhance its blood circulation and endow it with mitochondria-targeted specificity. α-Tocopherol succinate and indocyanine green are loaded in mitochondria-targeted mesoporous silica nanoparticles to reduce innate oxygen consumption by blocking mitochondrial respiration chain, leading to endogenous mitochondrial ROS burst and imaging-guided photodynamic therapy. This mitochondria-targeted oxidative stress amplifier not only disrupts mitochondrial redox homeostasis and triggers long-term high oxidative stress but also makes tumor more sensitive to hypoxia-resistant photodynamic therapy. The imaging-guided ROS amplifier confirms the feasibility and effectiveness of both in vitro and in vivo anticancer performance, suggesting a promising clinical strategy in hypoxia-related tumor treatment.

Cascaded Amplifier Nanoreactor for Efficient Photodynamic Therapy.

Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) to treat established diseases and has attracted growing attention in the field of cancer therapy. However, in a tumor microenvironment (TME), the inherent hypoxia and high level of antioxidants severely hamper the efficacy of ROS generation. Here, we describe a cascaded amplifier nanoreactor based on self-assembled nanofusiforms for persistent oxygenation to amplify ROS levels. The nanofusiform assembly is capable of photothermal and photodynamic treatment and regulation of redox oxidation stress by antioxidant depletion to prevent ROS tolerance. The Pt nanozyme decoration of the nanofusiform enables efficient oxygen supplements via Pt nanozyme-catalyzed decomposition of H2O2 overexpressed in TME and generation of O2. Furthermore, the temperature elevation resulted from the photothermal effect of the nanofusiform increases the catalase-like catalytic activity of the Pt nanozyme for boosted oxygen generation. Thus, such a triple cascade strategy using nanozyme-based nanofusiforms amplifies the ROS level by continuous oxygenation, enhancing the efficacy of PDT in vitro and in vivo. Meanwhile, an in vivo multi-modal imaging including near-infrared fluorescence imaging, photothermal imaging, and magnetic resonance imaging achieves precise tumor diagnosis. The rationally designed nanofusiform acts as an efficient ROS amplifier through multidimension strengthening of continuous oxygenation, providing a potential smart nanodrug for cancer therapy.

Highly selective and sensitive detection of trinitrotoluene by framework-enhanced fluorescence of gold nanoclusters.

Precise analysis of explosives is important for environmental pollution evaluation and terrorist prevention. However, rapid assay of explosives with high selectivity and sensitivity remains difficult. Here, we show that the gold nanocluster-modified metal-organic frameworks are excellent optical probes for explosive detection. The nanoclusters exhibit enhanced luminescence and selectively respond toward 2,4,6-trinitrotoluene over other explosives with a detection limit of 5 nM and fast response within 1 min. The efficient assay is resulted from the framework-mediated cluster aggregation and TNT binding.

Simultaneous Monitoring of Cell-surface Receptor and Tumor-targeted Photodynamic Therapy via TdT-initiated Poly-G-Quadruplexes.

Cancer cells contain a unique set of cell surface receptors that provide potential targets for tumor theranostics. Here, we propose an efficient approach to construct G-quadruplex-based aptamers that specifically recognize cell-surface receptors and monitor them in an amplified manner. This designed aptamer combined particular sequence for the c-Met on the cell surface and poly-G-quadruplexes structures that allow a rapid and amplified fluorescent readout upon the binding of thioflavin T (ThT). The poly-G-quadruplexes also function as a carrier for photosensitizers such as TMPyP4 in that, the aptamer further trigger the production of reactive oxygen species (ROS) to commit cells to death. This unique c-Met targeting aptamer enabled simultaneous monitoring of c-Met on the cell surface with ThT and photodynamic killing of these lung cancer cells with TMPyP4. This strategy is expected to enhance the development of tumor-targeted diagnosis and drug delivery.