Latest ArticlesRed emissive carbon dots (CDs) are highly desired for biological applications. However, serious luminescence quenching of red emissive CDs in aqueous solution greatly hinders their application in high performance biological imaging. Herein, we reported a facile strategy to realize enhanced red emission of CDs in aqueous solution by surface modification with polyetherimide (PEI) via microwave heating method. High photoluminescence quantum yield (PLQY) of 25% was realized from the PEI functionalized CDs (CDs@PEI) in aqueous solution. The proposed PEI functionalization strategy not only protects the red emission against water molecules quenching, but also reverses the surface charges from negativity to positivity to promote cellular uptake of CDs, leading to clear cell imaging in red fluorescence region. More important, CDs@PEI exhibits much better photostability than commercial red emissive dye (MitoTracker red) in cell fluorescent imaging. Potential application of CDs@PEI on fast staining of cells for clonogenic assay has also been demonstrated.
The paper describes a kind of truly full-color photoluminescence (PL) CDs. The CDs were prepared by using one-pot hydrothermally heating citric acid and formamide at 200 ℃ for 2 h. The CDs have three fluorescent centers at blue, green, and red light region. Their color was regulated through two means, including changing excitation wavelengths or CDs concentrations. The emission maxima changed from blue to red with the increase of excitation wavelengths or CDs concentrations. The full-color PL behavior of the CDs was inherited and conserved in the solid polymer matrix, giving multicolor CDs/polymer films and light emitting diodes (LEDs). White-light LED (WLED) with the CIE coordinate approaching to (0.31, 0.32) were also achieved.
Two novel seco-polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperbenzones A (1) and B (2), were isolated from the roots of Hypericum beanii, together with one known biosynthetic congener 3. Compound 1 incorporates a 6/5/5 ring system with an unprecedented spiro[bicyclo[3.3.0]octane-3,1ʹ-cyclohexane]-2,2ʹ-dione motif. The structures of 1 and 2 were determined by a combination of high resolution electrospray ionization mass spectroscopy (HRESIMS), nuclear magnetic resonance (NMR) spectroscopic analyses, gage-independent atomic orbital (GIAO) NMR chemical shift calculation with DP4+ analyses, electronic circular dichroism (ECD) calculation, and X-ray diffraction analysis. A 1,2-seco retro-Claisen rearrangement from a bicyclo[3.3.1]nonane PPAP precursor and following chemodivergent radical cascade cyclizations are proposed as the key steps in the biosynthetic pathway to yield compounds 1 and 2. Biological investigations indicated that compounds 1 and 3 could decrease intracellular lipid accumulation in a palmitic acid-induced nonalcoholic steatohepatitis (NASH) cell model.
Liquid biopsy is a highly promising method for non-invasive detection of tumor-associated nucleic acid fragments in body fluids but is challenged by the low abundance of nucleic acids of clinical interest and their sequence homology with the vast background of nucleic acids from healthy cells. Recently, programmable endonucleases such as clustered regularly interspaced short palindromic repeats (CRISPR) associated protein (Cas) and prokaryotic Argonautes have been successfully used to remove background nucleic acids and enrich mutant allele fractions, enabling their detection with deep next generation sequencing (NGS). However, the enrichment level achievable with these assays is limited by futile binding events and off-target cleavage. To overcome these shortcomings, we conceived a new assay (Programmable Enzyme-Assisted Selective Exponential Amplification, PASEA) that combines the cleavage of wild type alleles with concurrent polymerase amplification. While PASEA increases the numbers of both wild type and mutant alleles, the numbers of mutant alleles increase at much greater rates, allowing PASEA to achieve an unprecedented level of selective enrichment of targeted alleles. By combining CRISPR-Cas9 based cleavage with recombinase polymerase amplification, we converted samples with 0.01% somatic mutant allele fractions (MAFs) to products with 70% MAFs in a single step within 20 min, enabling inexpensive, rapid genotyping with such as Sanger sequencers. Furthermore, PASEA's extraordinary efficiency facilitates sensitive real-time detection of somatic mutant alleles at the point of care with custom designed Exo-RPA probes. Real-time PASEA' performance was proved equivalent to clinical amplification refractory mutation system (ARMS)-PCR and NGS when testing over hundred cancer patients' samples. This strategy has the potential to reduce the cost and time of cancer screening and genotyping, and to enable targeted therapies in resource-limited settings.
Quantitative information, such as environmental migration, absorption, biodistribution, biotransformation, and elimination, is fundamental and essential for the nanosafety evaluations of nanomaterials. Due to the complexity of biological and environmental systems, it is challenging to develop quantitative approaches and tools that could characterize intrinsic behaviors of nanomaterials in the organisms. The isotopic tracers are ideal candidates to tune the physical properties of nanomaterials while preserving their chemical properties. In this review article, we summarized the stable isotope labeling methods of nanomaterials for evaluating their environmental and biological effects. The skeleton labeling protocols of carbon nanomaterials and metal/metal oxide nanoparticles were introduced. The advantages and disadvantages of stable isotope labeling were discussed in comparison with other quantitative methods for nanomaterials. The quantitative information of nanomaterials in environmental and biological systems was summarized along with the biosafety data. The benefits for drug development of nanomedicine were analyzed based on the targeting effects, persistent accumulation, and safety. Finally, the challenges and future perspectives of stable isotope labeling in nanoscience and nanotechnology were discussed.
While radiotherapy is a mainstay therapeutic modality for malignant tumor, the intrinsic tumor resistance to radiotherapy, as well as the concomitant radiation injury to adjacent healthy tissues, greatly limits the efficacy of cancer radiotherapy. As a result, the development of novel radioenhancers and radioprotectants is highly desired for clinical radiotherapy. In recent years, nanozymes have inspired ever-growing research interest because of their multi-enzyme activities and microenvironment-responsive feature. In view of the significant progress of nanozymes in radiation medicine, we, in this review, systematically illustrate the impressive progress of nanozymes for potentiating radiotherapy and radiation protection. First, the types of nanozymes used in tumor radiotherapy are briefly discussed. Subsequently, the main strategies of nanozymes to enhance the radiotherapy efficiency, including promoting the generation of reactive oxygen species (ROS), relieving hypoxia in tumor microenvironment and combining with other cancer therapeutic regimens, are summarized. Finally, the advances of typical nanozymes for preventing radiation-induced hematopoietic damage and gastrointestinal damage are highlighted.
Astatine-211 (211At, t1/2 = 7.21 h) emitting two α particles with energies of 5.87 and 7.45 MeV, can lead to a high linear energy transfer (LET = 98.84 keV/µm) and short tissue range (50~90 µm). Since the 1950s, 211At had stepped into endoradiotherapy and has always been regarded as one of the most promising α-emitters for targeted-alpha therapy (TAT) in various malignancies. In the past two decades, 211At related radiopharmaceuticals have achieved great progress in the studies of basic physicochemical properties of astatine, 211At labeling strategies, preclinical and clinical studies, producing profound effects in nuclear medicine. This work will give a panorama of 211At-related researches in the recent 20 years, which will cover both the fundamental insights of 211At radiochemistry and applied labeling compounds. It can provide some important hints for the studies of TAT and other radiopharmaceuticals applied in tumor radiotherapy.
Abnormal Tau deposition is a crucial pathological hallmark of various neurodegenerative disorders defined as tauopathies, of which Alzheimer's disease is the most prominent one. To date, a large number of chemical entities with different structures have been developed as Tau imaging tracers for the early diagnosis of tauopathies. Several of them with excellent bio-properties are currently being assessed in clinical trials, and more recently, the TauvidTM ([18F]Flortaucipir, also known as [18F]AV1451 or [18F]T807) as the first Tau tracer was approved by the U.S. Food and Drug Administration in 2020. This review summarized the latest development of Tau tracers and analyzed their chemical structures, with particular attention to the effects of chemical structures on biological properties. In addition, we also discuss the limitations of current Tau imaging tracers, issues that need attention in the development of new tracers, and possible future directions.
The prevalence of positron emission tomography (PET) imaging has advanced biomedical applications for its ultrahigh sensitivity, deep tissue penetration and quantitative visualization of diseases in vivo. 64Cu with ideal half-life and decay characteristics has been designed as radioactive probes for disease diagnosis. The currently reported 64Cu-labeled nanomaterials have the advantages of long circulation time in serum, good biocompatibility and mature preparation methods, and have been used in vivo PET imaging, biodistribution and pharmacokinetic monitoring, and imaging guided therapy. At the same time, suitable carrier characteristics and radiolabeling strategies are particularly important in the 64Cu PET imaging process. In this review, we summarize different imaging probe designs and 64Cu radiolabeling strategies, as well as their eventual applications in biomedicine. The potential challenges and prospects of 64Cu labeled nanomaterials are also described, which provides broad prospects for radiolabeling strategies and further applications.
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