Targeting Nanomotor with Near-Infrared/Ultrasound Triggered-Transformation for Polystage-Propelled Cascade Thrombolysis and Multimodal Imaging Diagnosis.

Nowadays, cardiovascular and cerebrovascular diseases caused by venous thromboembolism become main causes of mortality around the world. The current thrombolytic strategies in clinics are confined primarily due to poor penetration of nanoplatforms, limited thrombolytic efficiency, and extremely-low imaging accuracy. Herein, a novel nanomotor (NM) is engineered by combining iron oxide/perfluorohexane (PFH)/urokinase (UK) into liposome nanovesicle, which exhibits near-infrared/ultrasound (NIR/US) triggered transformation, achieves non-invasive vein thrombolysis, and realizes multimodal imaging diagnosis altogether. Interestingly, a three-step propelled cascade thrombolytic therapy is revealed from such intelligent NM. First, the NM is effectively herded at the thrombus site under guidance of a magnetic field. Afterwards, stimulations of NIR/US propel phase transition of PFH, which intensifies penetration of the NM toward deep thrombus dependent on cavitation effect. Ultimately, UK is released from the collapsed NM and achieves pharmaceutical thrombolysis in a synergistic way. After an intravenous injection of NM in vivo, the whole thrombolytic process is monitored in real-time through multimodal photoacoustic, ultrasonic, and color Doppler ultrasonic imagings. Overall, such advanced nanoplatform provides a brand-new strategy for time-critical vein thrombolytic therapy through efficient thrombolysis and multimodal imaging diagnosis.

Dual-Modal Imaging and Synergistic Spinal Tumor Therapy Enabled by Hierarchical-Structured Nanofibers with Cascade Release and Postoperative Anti-adhesion.

Most treatments for spinal cancer are accompanied by serious side effects including subsequent tumor recurrence, spinal cord compression, and tissue adhesion, thus a highly effective treatment is crucial for preserving spinal and neurological functionalities. Herein, trilayered electrospun doxorubicin@bovine serum albumin/poly(ε-caprolactone)/manganese dioxide (DOX@BSA/PCL/MnO2) nanofibers with excellent antiadhesion ability, dual glutathione/hydrogen peroxide (GSH/H2O2) responsiveness, and cascade release of Mn2+/DOX was fabricated for realizing an efficient spinal tumor therapy. In detail, Fenton-like reactions between MnO2 in the fibers outermost layer and intra-/extracellular glutathione within tumors promoted the first-order release of Mn2+. Then, sustained release of DOX from the fibers' core layer occurred along with the infiltration of degradation fluid. Such release behavior avoided toxic side effects of drugs, regulated inflammatory tumor microenvironment, amplified tumor elimination efficiency through synergistic chemo-/chemodynamic therapies, and inhibited recurrence of spinal tumors. More interestingly, magnetic resonance and photoacoustic dual-modal imaging enabled visualizations of tumor therapy and material degradation in vivo, achieving rapid pathological analysis and diagnosis. On the whole, such versatile hierarchical-structured nanofibers provided a reference for rapid and potent theranostic of spinal cancer in future clinical translations.

Four New Compounds Obtained from Cultured Cells of Artemisia annua.

Four new compounds obtained from cultured cells of Artemisia annua were reported. Products were detected by HPLC-ELSD/GC-MS and isolated by chromatographic methods. The structures of four new compounds, namely 6-hydroxy arteannuin I (1), 1-hydroxy arteannuin I (2), 2-hydroxy arteannuin J (3), and 14-hydroxy arteannuin J (4), were elucidated using their physico-chemical properties by NMR and MS data analyses. The results from the spontaneous oxidative experiment indicated that the biosynthesis of the new compounds was enzyme-catalyzed. Interestingly, the enzymes in the cultured cells of A. annua showed the abilities of substrate-selective and region-selective hydroxylation of the sesquiterpene lactone. Furthermore, the artemisinin contents were increased by 50% and 80% compared to the control group after the addition of arteannuin I/J to the suspension-cultured cells of A. annua under light and dark culture conditions, respectively.