Bioorthogonal decaging reactions for controllable drug activation within complex biological systems are highly desirable yet extremely challenging. Herein, we find a new class of Pt(II)-triggered bioorthogonal cleavage reactions in which Pt(II) but not Pt(IV) complexes effectively trigger the cleavage of O/Npropargyl in a variety of ranges of caged molecules under biocompatible conditions. Based on these findings, we propose a general strategy for integrated bioorthogonal prodrugs and accordingly design a prodrug 16, in which a Pt(IV) moiety is covalently connected with an O 2 -propargyl diazeniumdiolate moiety. It is found that 16 can be specifically reduced by cytoplasmic reductants in human ovarian cancer cells to liberate cisplatin, which subsequently stimulates the cleavage of O 2 -propargyl to release large amounts of NO in situ, thus generating synergistic and potent tumor suppression activity in vivo. Therefore, Pt(II)-triggered depropargylation and the integration concept might provide a general strategy for broad applicability of bioorthogonal cleavage chemistry in vivo.
Multi-parametric photoacoustic microscopy (PAM) has emerged as a promising new technique for high-resolution quantification of hemodynamics and oxygen metabolism in the mouse brain. In this work, we have extended the scope of multi-parametric PAM to longitudinal, cortex-wide, awake-brain imaging with the use of a long-lifetime (24 weeks), wide-field (5 × 7 mm2), light-weight (2 g), dual-transparency ( i.e., light and ultrasound) cranial window. Cerebrovascular responses to the window installation were examined in vivo, showing a complete recovery in 18 days. In the 22-week monitoring after the recovery, no dura thickening, skull regrowth, or changes in cerebrovascular structure and function were observed. The promise of this technique was demonstrated by monitoring vascular and metabolic responses of the awake mouse brain to ischemic stroke throughout the acute, subacute, and chronic stages. Side-by-side comparison of the responses in the ipsilateral (injury) and contralateral (control) cortices shows that despite an early recovery of cerebral blood flow and an increase in microvessel density, a long-lasting deficit in cerebral oxygen metabolism was observed throughout the chronic stage in the injured cortex, part of which proceeded to infarction. This longitudinal, functional-metabolic imaging technique opens new opportunities to study the chronic progression and therapeutic responses of neurovascular diseases.
The accumulation of plastic wastes in landfills and the environment threatens our environment and public health, while leading to the loss of potential carbon resources. The urgent necessary lies in developing an energy‐saving and environmentally benign approach to upgrade plastic into value‐added chemicals. Artificial photosynthesis holds the ability to realize plastic upcycling by using endless solar energy under mild conditions, but remains in the initial stage for plastic upgrading. In this review, we aim to look critically at the photocatalytic conversion of plastic wastes from the perspective of resource reutilization. To begin with, we present the emerging conversion routes for plastic wastes and highlight the advantages of artificial photosynthesis for processing plastic wastes. By parsing photocatalytic plastic conversion process, we demonstrate the currently available routes for processing plastic, including plastic photodegradation, tandem decomposition of plastic and CO2 reduction, selective plastic oxidation, as well as photoreforming of plastic. This review concludes with a personal perspective for potential advances and emerging challenges in photocatalytic plastic conversion.
Breast cancer (BC) is the most common malignancy among females worldwide, and high resistance to drugs and metastasis rates are the leading causes of death in BC patients. Releasing anti-cancer drugs precisely to the tumor site can improve the efficacy and reduce the side effects on the body. Natural polymers are attracting extensive interest as drug carriers in treating breast cancer. Hyaluronic acid (HA) is a natural polysaccharide with excellent biocompatibility, biodegradability, and non-immunogenicity and is a significant component of the extracellular matrix. The CD44 receptor of HA is overexpressed in breast cancer cells and can be targeted to breast tumors. Therefore, many researchers have developed nano drug delivery systems (NDDS) based on the CD44 receptor tumor-targeting properties of HA. This review examines the application of HA in NDDSs for breast cancer in recent years. Based on the structural composition of NDDSs, they are divided into HA NDDSs, Modified HA NDDSs, and HA hybrid NDDSs.
3a can be triggered by BTZ and then liberate NO and acrolein. By liposomes of 3a and BTZ, the bioorthogonal reactions between them was limited within the implanted cancer cells in zebrafish, thus generating potent cancer inhibitory activity.
Objective: The purpose of this study was to evaluate the therapeutic efficacy and safety of superselective renal arterial embolization (SRAE) in the treatment of patients with renal hemorrhage after percutaneous nephroscopy (PCNL). In addition, embolization techniques and embolization materials during operation were also worthy of further discussion.Methods: From February 2015 to December 2019, clinical data of 49 consecutive patients with renal hemorrhage after PCNL were retrospectively analyzed. Demographic and clinical data of patients were recorded, changes in serum creatinine values were analyzed, and the safety and efficacy of TAE were evaluated. Clinical experience was also recorded.Results: A total of 49 patients underwent angiography, of which 46 patients received SRAE due to positive hemorrhagic foci detected by angiography, and the technical success rate of 46 patients was 100%. Among the three patients who did not receive embolization, one patient underwent nephrectomy, and two patients improved with conservative treatment, with a clinical success rate of 98%. There was no statistically significant difference between serum creatinine before PCNL and 7 days after SRAE (101.6 ± 36.5 to 100.5 ± 27.1 μmol/L; P = 0.634), and no significant change was observed in serum creatinine at the last follow-up (99.4 ± 34 μmol/L, P = 0.076). No major complications occurred after embolization.Conclusions: SRAE is safe and effective in patients with renal hemorrhage after PCNL. The experience of interventional therapy and the choice of embolization materials in this study may provide certain benefits for the treatment of patients with renal hemorrhage after PCNL.
The treatment of ischemic stroke (IS) remains a big challenge in clinics, and it is urgently needed to develop novel, safe, and effective medicines against IS. Here, we report the design, synthesis, and biological evaluation of organic NO 2 − donors as potential agents for the treatment of IS. The representative compound 4a was able to slowly generate low concentrations of NO 2 − by reaction with a thiol-containing nucleophile, and the NO 2 − was selectively converted into NO under ischemic/hypoxia conditions to protect primary rat neurons from oxygen−glucose deprivation and recovery (OGD/R)-induced cytotoxicity by enhancing the Nrf2 signaling and activating the NO/cGMP/PKG pathway. Treatment with 4a at 2 h before or after ischemia mitigated the ischemia/ reperfusion-induced brain injury in middle cerebral artery occlusion (MCAO) rats by producing NO and enhancing Nrf2 signaling. Furthermore, 4a significantly promoted endothelial cell proliferation and angiogenesis within the ischemic penumbra. Our findings suggest that this type of NO 2 − donors, like 4a, may be valuable to fight IS and other ischemic diseases.
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