Atomically precise photothermal nanomachines.

Interfacing molecular machines to inorganic nanoparticles can, in principle, lead to hybrid nanomachines with extended functions. Here we demonstrate a ligand engineering approach to develop atomically precise hybrid nanomachines by interfacing gold nanoclusters with tetraphenylethylene molecular rotors. When gold nanoclusters are irradiated with near-infrared light, the rotation of surface-decorated tetraphenylethylene moieties actively dissipates the absorbed energy to sustain the photothermal nanomachine with an intact structure and steady efficiency. Solid-state nuclear magnetic resonance and femtosecond transient absorption spectroscopy reveal that the photogenerated hot electrons are rapidly cooled down within picoseconds via electron-phonon coupling in the nanomachine. We find that the nanomachine remains structurally and functionally intact in mammalian cells and in vivo. A single dose of near-infrared irradiation can effectively ablate tumours without recurrence in tumour-bearing mice, which shows promise in the development of nanomachine-based theranostics.

Azo Reductase Activated Magnetic Resonance Tuning Probe with "Switch-On" Property for Specific and Sensitive Tumor Imaging in Vivo.

Cancer remains a threat to human health. However, if tumors can be detected in the early stage, then the effectiveness of cancer treatment could be significantly improved. Therefore, it is worthwhile to develop more sensitive and accurate cancer diagnostic methods. Herein, we demonstrated an azo reductase (AzoR)-activated magnetic resonance tuning (MRET) probe with a "switch-on" property for specific and sensitive tumor imaging in vivo. Specifically, Gd-labeled DNA1 (DNA1-Gd) and cyclodextrin-coated magnetic nanoparticles (MNP-CD) were employed as enhancer and quencher of MRET, respectively, while DNA2, an azobenzene (Azo) group-modified aptamer (AS1411), served as a linker between enhancer and quencher to construct the MRET probe of MNP@DNA(1-2)-Gd. In tumor tissues with high-level AzoR, the T1-weighted magnetic resonance signal of the MRET probe could be restored by intelligently regulating the switch from "OFF" to "ON" after activation with AzoR, thus accurately indicating the location of the tumor accurately. Moreover, the tumor with a 4 times smaller size than that of the normal tumor model could be imaged based on the proposed MRET probe. The as-proposed MRET-based magnetic resonance imaging strategy not only achieves tumor imaging accurately but also shows promise for early diagnosis of tumors, which might improve patients' survival rates and provide an opportunity for image-guided biomedical applications in the future.

ADAMTS5 promotes neovascularization via autophagic degradation of PEDF in proliferative diabetic retinopathy.

Proliferative diabetic retinopathy (PDR) adversely affects visual function. Extracellular matrix proteins (ECM) contribute significantly to the development of PDR. A Disintegrin and Metalloproteinase with Thrombospondin motifs 5 (ADAMTS5) is a member of ECM proteins. ADAMTS5 participates in angiogenesis and inflammation in diverse diseases. However, the role of ADAMTS5 in PDR remains elusive. Multiplex beam array technology was used to analyze vitreous humor of PDR patients and normal people. ELISA and Western blot were used to detect the expression of ADAMTS5, PEDF and autophagy related factors. Immunofluorescence assay was used to mark the expression and localization of ADAMTS5 and PEDF. The neovascularization was detected by tube formation test. Our results revealed that ADAMTS5 expression was increased in the vitreous humor of PDR patients and oxygen-induced retinopathy (OIR) mice retinas. Inhibiting ADAMTS5 alleviated pathological angiogenesis and upregulated PEDF expression in the OIR mice. In addition, ADAMTS5 inhibited PEDF secretion in ARPE-19 cells in vitro studies, thereby inhibiting the migration of HMEC-1. Mechanically, ADAMTS5 promoted the autophagic degradation of PEDF. Collectively, inhibition of ADAMTS5 during OIR suppresses pathological angiogenesis. Our study provides a new approach for resolving pathological angiogenesis in PDR.

Gold Nanoparticles Encapsulated Resveratrol as an Anti-Aging Agent to Delay Cataract Development.

Nanoparticle-based drug delivery systems, which can overcome the challenges associated with poor aqueous solubility and other harmful side effects of drugs, display potent applications in cataract treatment. Herein, we designed a nanosystem of gold nanoparticles containing resveratrol (RGNPs) as an anti-aging agent to delay cataracts. The spherical RGNPs had a superior ability to inhibit hydrogen peroxide-mediated oxidative stress damage, including reactive oxygen species (ROS) production, malondialdehyde (MDA) generation, and glutathione (GSH) consumption in the lens epithelial cells. Additionally, the present data showed that RGNPs could delay cellular senescence induced by oxidative stress by decreasing the protein levels of p16 and p21, reducing the ratio of BAX/BCL-2 and the senescence-associated secretory phenotype (SASP) in vitro. Moreover, the RGNPs could also clearly relieve sodium selenite-induced lens opacity in a rat cataract model. Our data indicated that cell senescence was reduced and cataracts were delayed upon treatment with RGNPs through activating the Sirt1/Nrf2 signaling pathway. Our findings suggested that RGNPs could serve as an anti-aging ingredient, highlighting their potential to delay cataract development.

Bacteria-Targeted MRI Probe-Based Imaging Bacterial Infection and Monitoring Antimicrobial Therapy In Vivo.

Despite the significant advances of imaging techniques nowadays, accurate diagnosis of bacterial infections and real-time monitoring the efficacy of antibiotic therapy in vivo still remain huge challenges. Herein, a self-assembling peptide (FFYEGK) and vancomycin (Van) antibiotic molecule co-modified gadolinium (Gd) MRI nanoaggregate probe (GFV) for detecting Staphylococcus aureus (S. aureus) infection in vivo and monitoring the treatment of S. aureus-infected myositis by using daptomycin (Dap) antibiotic as model are designed and fabricated. The as-prepared GFV probe bears Van molecules, making itself good bacteria-specific targeting, and the peptide in the probe can enhance the longitudinal relaxivity rate (r1 ) after self-assembly due to the π-π stacking. The study showed that, based on the GFV probe, bacterial infections and sterile inflammation can be discriminated, and as few as 105 cfu S. aureus can be detected in vivo with high specificity and accurately. Moreover, the T1 signal of GFV probe at the S. aureus-infected site in mice correlates with the increasing time of Dap treating, indicating the possibility of monitoring the efficacy of antibacterial agents for infected mice based on the as proposed GFV probe. This study shows the potential of GFV probe for diagnosis, evaluation, and prognosis of infectious diseases in clinics.

[Development in Tissue Clearing Technology and Its Application in Neurodegenerative Diseases].

Modern tissue clearing techniques have made it possible to have high-resolution imaging of cell populations and three-dimensional reconstruction of tissue structures, and we are able to obtain more complete three-dimensional brain structures and spatial connections between the various components of brain tissues through tissue clearing techniques. Over the past decade, scientists have developed and improved a number of tissue clearing techniques that are now widely used in neuroscience research, allowing us to extract important information from complex neural networks. Moreover, tissue clearing technology also provides research tools for the stem cell therapy and neurogeneration of neurodegenerative diseases. In this paper, we reviewed the major types of existing tissue clearing techniques and their respective strengths and weaknesses. We summarized the application of these techniques in neurodegenerative disease research and their unique merits. In addition, we explored the development requirements of tissue clearing technology, improvements in the supporting equipment, and its potential to be used as research tools for stem cell therapy and regenerative medicine in the future.

Immunostimulatory AIE Dots for Live-Cell Imaging and Drug Delivery.

The mechanical properties of nanoscale drug carriers play critical roles in regulating nano-bio interactions. For example, the superior deformability of the softer nanoparticles enables them to pass through the biofilters efficiently, facilitating their long blood circulation and better tumor penetration. However, as a novel nanocarrier system, the elimination efficiency of soft nanoparticles from cells is poorly investigated. Here, we report a facile strategy to prepare soft luminescent nanoparticles through self-assembly of amphiphilic aggregation-induced emission (AIE) fluorophores. The prepared soft AIE dots exhibit strong light emission (quantum yield, ∼27.1%) and can reveal the encapsulation and excretion process of NPs in real time. The cell results showed that soft NPs can greatly increase the transfer speed of nanomaterials into cells and accelerate their elimination from cells through the sacrifice of soft AIE dots. We also show that soft AIE dots loaded with cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can induce strong immunostimulatory effects, producing a high level of various proinflammatory cytokines including tumor necrosis factor (TNF)-R, interleukin (IL)-6, and IL-12. This work demonstrates a new design strategy for synthesizing a soft nanocarrier system that can deliver drugs into cells efficiently and then be eliminated from cells quickly.

Gold nanoflower-based surface-enhanced Raman probes for pH mapping of tumor cell microenviroment.

OBJECTIVES: Early diagnosis of tumour cells is critically important for cancer treatment. Given that the tumour environment is slightly acidic, the pH value of the cell environment can be used as a criterion for tumour diagnosis. However, mapping pH in the cell environment with high resolution, high sensitivity and accuracy remains challenging. MATERIALS AND METHODS: Based on gold nanoflower as surface-enhanced Raman scattering (SERS) substrate loading with p-mercaptobenzoic acid (MPA) as pH-responsive Raman reporter, a new SERS nanoprobe for pH mapping was developed. RESULTS: This probe showed a characteristic Raman spectrum signal in response to the different pH in solutions or cells. The signal intensity is positively correlated to the pH value. Moreover, this probe is self-correctable, which can help eliminate the influence of probe concentration on the accuracy of pH measuring. CONCLUSIONS: We demonstrate the pH mapping of cell environment using the probe, which can be used to distinguish normal cells and tumour cells. This method may provide a new imaging tool for early diagnosis of cancer.

Synthesis and preliminary evaluation of 18F-icotinib for EGFR-targeted PET imaging of lung cancer.

Epidermal growth factor receptor (EGFR) has emerged as an attracting target in the field of imaging and treatment for non-small cell lung cancer (NSCLC). Radiolabeled EGFR-tyrosine kinase inhibitors (EGFR-TKIs) specifically targeting EGFR are deemed as promising probes for the imaging of NSCLC. This study aimed to label icotinib (one kind of EGFR-TKI) with 18F through click reaction to develop a new EGFR-targeting PET probe-18F-icotinib. 18F-icotinib was obtained in 44.81% decay-corrected yield in 100 min synthesis time with 34 GBq/µmol specific activity and >99% radiochemical purity at the end of synthesis. The identity of the product was confirmed by co-injection with 18F-icotinib and 19F-icotinib. The Log P was 1.28 ±â€¯0.04 (n = 6). The tracer displayed excellent stability after incubation for 4 h in vitro. 18F-icotinib showed satisfying binding ability to A549 NSCLC cells, which could be inhibited by icotinib. PET imaging studies demonstrated a specific uptake of the radiotracer (0.90 ±â€¯0.24% ID/g) in A549 tumor-bearing mice, while lower uptake was observed in heart, lung and spleen at 1.5 h post injection. Inmunohistochemical staining confirmed that the A549 tumor was EGFR-positive. Therefore, we considered that 18F-icotinib was a highly promising compound for EGFR-based tumor PET imaging.