Despite the growing application of tetrazine bioorthogonal chemistry, it is still challenging to access tetrazines conveniently from easily available materials. Described here is the de novo formation of tetrazine from nitriles and hydrazine hydrate using a broad array of thiol‐containing catalysts, including peptides. Using this facile methodology, the syntheses of 14 unsymmetric tetrazines, containing a range of reactive functional groups, on the gram scale were achieved with satisfactory yields. Using tetrazine methylphosphonate as a building block, a highly efficient Horner–Wadsworth–Emmons reaction was developed for further derivatization under mild reaction conditions. Tetrazine probes with diverse functions can be scalably produced in yields of 87–93 %. This methodology may facilitate the widespread application of tetrazine bioorthogonal chemistry.

The blood–brain tumor barrier (BTB) and blood–brain barrier (BBB) have always been the major barriers in glioma therapy. In this report, we proposed D-T7 peptide-modified nanoparticles actively targeted glioma by overcoming the BBB and BTB to improve the antiglioma efficacy. Glioma-targeting experiments showed that the penetration effect of the D-T7 peptide-modified nanoparticles was 7.89-fold higher than that of unmodified nanoparticles. Furthermore, cediranib (CD) and paclitaxel (PTX) were used for the combination of the antiangiogenesis and chemotherapy for glioma. PEGylated bilirubin nanoparticles (BRNPs) were selected as a suitable drug delivery system (CD&PTX@TBRBPs) owing to the antioxidant, anti-inflammatory, and reactive oxygen species-responsive ability. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis assays showed that CD&PTX@TBRBPs had the highest cytotoxicity and the median survival time of the CD&PTX@TBRNP group was 3.31-fold and 1.23-fold longer than that of the saline and CD&PTX@BRNP groups, respectively. All the results showed that we constructed a novel and accessible peptide-modified dual drug carrier with an enhanced antiglioma effect.

Despite the growing application of tetrazine bioorthogonal chemistry,itisstill challenging to access tetrazines conveniently from easily available materials.Described here is the de novo formation of tetrazine from nitriles and hydrazine hydrate using ab road array of thiol-containing catalysts, including peptides.Using this facile methodology,the syntheses of 14 unsymmetric tetrazines,c ontaining ar ange of reactive functional groups,o nt he gram scale were achieved with satisfactory yields.U sing tetrazine methylphosphonate as ab uilding block, ah ighly efficient Horner-Wadsworth-Emmons reaction was developed for further derivatization under mild reaction conditions.T etrazine probes with diverse functions can be scalably produced in yields of 87-93 %. This methodology may facilitate the widespread application of tetrazine bioorthogonal chemistry.

Alzheimer's disease (AD) is a high mortality and high disability rates neurodegenerative disease characterized by irreversible progression and poses a significant social and economic burden throughout the world. However, currently approved AD therapeutic agents only alleviate symptoms and there is still a lack of practical therapeutic regimens to stop or slow the progression of this disease. Thus, there is urgently needed novel diagnosis tools and drugs for early diagnosis and treatment of AD. Among several AD pathological hallmarks, amyloid-β (Aβ) peptide deposition is considered a critical initiating factor in AD. In recent years, with the advantages of excellent sensitivity and high resolution, near-infrared fluorescence (NIRF) imaging has attracted the attention of many researchers to develop Aβ plaque probes. This review mainly focused on different NIRF probe design strategies for imaging Aβ species to pave the way for the future design of novel NIRF probes for early diagnosis AD.

Fluorophores with different emission wavelengths were efficiently quenched by tert-butyl terminated tetrazylmethyl group and activated by isonitrile-tetrazine click-to-release reaction. Nucleic acid templated chemistry significantly accelerated this bioorthogonal cleavage. Moreover, two...

Objective To investigate the impact of 68Gallium prostate‐specific membrane antigen (68Ga‐PSMA) tracers on the management of prostate cancer (PCa) patients with biochemical recurrence (BCR) by conducting a systematical review and meta‐analysis. Materials and Methods We performed a literature search of the PubMed, Embase and Web of Science databases up to 29 October 2019. We included studies that reported the proportion of patients whose management changed after 68Ga‐PSMA tracers were used in patients with BCR. We used the Quality Assessment of Diagnostic Accuracy Studies‐2 tool to evaluate the quality of the included studies. The proportion of patients with management changes were pooled using a random‐effects model. Subgroup analyses and meta‐regression analyses were performed to explore the source of heterogeneity. A Sankey diagram was used to show treatment change from before to after the use of 68Ga‐PSMA tracers. Results We included 20 eligible studies (2026 patients). The pooled proportion of patients with management change was 53% (95% confidence interval [CI] 46–60) in patients with BCR and 51% (95% CI, 34–67) in patients with early BCR (prostate‐specific antigen [PSA] <0.5 ng/mL). The pooled positron‐emission tomography‐positive rate in patients with BCR was 68% (95% CI 59–78). Fourteen studies reported management change, with most changes being intermodal in nature (42%, vs 17% intramodal change). Conclusions The use of 68Ga‐PSMA tracers altered the management of more than half of PCa patients with BCR, including those with early BCR. 68Ga‐PSMA tracers might be used to guide individualized treatment in patients with BCR, particularly those with early BCR.

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