Latest ArticlesTriple-negative breast cancer, due to its aggressive nature and lack of targeted treatment, faces serious challenges in breast cancer treatment. Conventional therapies, such as chemotherapy, are encumbered by a range of limitations, and there is an urgent need for more effective treatment strategies. Ferroptosis, as an iron-dependent form of cell death, has exhibited promising potential in cancer treatment. Combining ferroptosis with other cancer therapies offers new avenues for treatment. Tetrahedral DNA nanostructure (TDN), a novel DNA-based three-dimensional (3D) nanomaterial, is promising drug delivery vehicle and can be utilized for functionalizing inorganic nanomaterials. In this work, we have demonstrated the preparation of Fe3O4-PEI@TDN-DOX nanocomposites and elucidated their antitumor mechanism. The TDN facilitated the enhanced cellular uptake of polyetherimide (PEI)-modified Fe3O4, and the delivery of the chemotherapeutic drug doxorubicin (DOX) further augmented their anti-tumor effect. This novel strategy can destroy the tumor redox homeostasis and produce overwhelming lipid peroxides, consequently sensitizing the tumor to ferroptosis. The integration of ferroptosis with other cancer therapies opens up new possibilities for treatment. This research provides valuable mechanistic insights and practical strategies for leveraging nanotechnology to induce ferroptosis and amplify its impact on tumor cells.
For the first time, proteolysis-targeting chimeras (PROTAC) technology was utilized to achieve the isoform-selective degradation of class Ⅰ phosphoinositide 3-kinases (PI3Ks) in this study. Through screening and optimization, the PROTAC molecule ZM-PI05 was identified as a selective degrader of p110α in multiple breast cancer cells. More importantly, the degrader can down-regulate p85 regulatory subunit simultaneously, thereby inhibiting the non-enzymatic functions of PI3K that are independent on p110 catalytic subunits. Therefore, compared with PI3K inhibitor copanlisib, ZM-PI05 displayed the stronger anti-proliferative activity on breast cancer cells. In brief, a selective and efficient PROTAC molecule was developed to induce the degradation of p110α and concurrent reduction of p85 proteins, providing a tool compound for the biological study of PI3K-α by blocking its enzymatic and non-enzymatic functions.
Adenosine triphosphate (ATP), known as a common metabolic product in organism, is not only importance to provide energy in various cellular activities but also is widely explored in the bio-inspired synthetic supramolecular area which becomes a fascinating topic with the rapid development of biology, chemistry and materials science. In this review, the recent advances about ATP interacted with functional small organic compounds and metal coordinated complexes are summarized. The design principles, its function as an active supramolecular matrix, the associated non-covalent binding modes and assembly induced properties including the optical properties, morphologies are presented in details. Besides, their applications for metal ion detecting, enzyme activity monitoring and drug delivery are described due to their excellently dynamic assembly properties, adjustability, and response to stimuli. Finally, an overview of the existing challenges and future prospects of ATP-induced supramolecular systems are also discussed.
Endogenous metabolites play key functions in many important physiological and biochemical processes. The comprehensive in situ detection and direct imaging of metabolites in bio-tissues by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is very important for understanding complex and diverse biological processes and has become an essential aspect of spatial omics. In this work, 4-aminoazobenzene (AAB) was successfully screened and optimized as a new negative ion (−)MALDI matrix to enhance the in situ detection and imaging of metabolites in tissues using MALDI-MSI. Obviously, AAB exhibited superior properties in terms of ultraviolet absorption, background ion interference, matrix morphology, and metabolite ionization efficiency. AAB was used for in situ detection and imaging of metabolites in rat brain and germinating Chinese yew seed tissue sections, where 264 and 339 metabolite ion signals were successfully detected and imaged using (-)MALDI-MS, respectively. In addition, high-resolution imaging of mouse eyeball section using MALDI-timsTOF MSI with spatial resolution of up to 10 µm was successfully carried out, showing that AAB is an efficient (-)MALDI matrix for capturing high-resolution images of metabolites in biological tissue sections.
Dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is the most promising target for diabetes treatment by promoting β-cell proliferation. The desmethylbellidifolin (DMB) as a DYRK1A inhibitor could facilitate β-cell proliferation in vivo and in vitro. However, DMB has the problem of weak binding affinity to DYRK1A, which means that continuous high concentration administration of DMB is effective for the diabetes. In order to solve this problem, we designed and synthesized a series of DMB-based proteolysis targeting chimeras (PROTACs) by taking advantage of the property of PROTAC that induce protein degradation in a cycle-catalytic manner. MDM2-based PROTAC X1–4P-MDM2 was identified as the most active PROTAC molecule. Mechanism research showed that X1–4P-MDM2 formed a ternary complex with DYRK1A and murine double minute 2 (MDM2), and induced the degradation of DYRK1A through the ubiquitin-proteasome system pathway. At a dose much lower than that of DMB, X1–4P-MDM2 still significantly enhanced β-cell proliferation by inhibiting transforming growth factor beta (TGF-β) and promoting the mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, which may provide a new strategy for the application of DMB in diabetes.
Electrochemiluminescence has been developed as a robust analytical technique owing to its intrinsic advantages, such as near-zero background signal noise, wide dynamic ranges, high sensitivity and low cost and simple equipment. ECL luminophore as the critical component to generate light signals plays significant roles in this robust analytical system. Compared with traditional ECL luminophores, near infrared (NIR) ECL luminophores have attracted significant attentions recently due to their negligible autofluorescence, lower background interference and deep tissue penetration. Although substantial progresses have been achieved in exploring novel NIR ECL luminophores and elucidating their roles in addressing diverse challenges, there is still scarce of comprehensive reviews on the development of NIR ECL luminophores so far. In this review, the recent advancements on NIR ECL materials, including inorganic metal complexes, organic small molecules, metal nanoclusters, quantum dots and lanthanide-based materials, have been thoroughly summarized and discussed. In addition, we also provide a comprehensive overview of the challenges and prospects that lie ahead for the future development of NIR ECL luminophores in the future.
Skin wound healing is an important aspect of regenerative medicine. Metal-organic frameworks (MOFs) have attracted considerable attention as promising nanomaterials for skin wound healing due to their remarkable versatility, tunable pore size, surface area, targeted delivery of various therapeutic agents, and controlled release properties. The combination of these materials with biocompatible and synthetic polymers can help improve their performance in wound regeneration. This review examines the potential of MOF-polymer composites in skin wound healing. Physical and biological chemical properties and methods of making MOFs and their composites have been investigated. In the final section of this review, challenges and future prospects for the development of MOF-polymer composites are stated.
Nitrogen-doped carbon (N–C) materials have demonstrated exceptional performances in activating peroxymonosulfate (PMS) for environmental remediation. However, accommodating higher nitrogen contents remains challenging in N–C due to the thermodynamic instability of C–N skeleton. In this study, we proposed an innovative epitaxial growth approach to synthesize two-dimensional N–C nanosheets. Leveraging the abundant amino groups supplied by the polymer dots as growing sites, we successfully attained a high nitrogen level and spontaneously introduced abundant structural defects in the carbon framework. The resulting N–C nanosheets exhibited outstanding catalytic activity for the activation of PMS toward selective oxidation of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (1,4-DHP) into diethyl 2,6-dimethylpyridine-3,5-dicarboxylate, which serves as a valuable intermediate in the synthesis of various pharmaceutical compounds. Comprehensive experimental and characterization investigations verified that the nitrogen sites and defects are the primary active sites for PMS activation and selective oxidation of 1,4-DHP. This work offered an efficient approach for the fabrication of high-nitrogen-loading carbon materials for catalytic oxidation reactions.
With the increasing demand for personalized and precise treatment, the rapid advancement of synthetic biology technology has inevitably led to the development of nanobiology-based drug delivery systems. Synthetic biology-based drug delivery systems are being increasingly used in the treatment of various diseases. On one hand, synthetic biology technology enables the clever combination of chassis cells, bacteria, and their derivatives with nanomaterials, forming nano-artificial hybrid systems. These systems effectively integrate the functions of both materials, leading to further breakthroughs and optimization of biological functions. On the other hand, synthetic biology strategies guide the self-assembly of modular nanocomponents with biocatalytic or intelligent response functions, resulting in the mimicry of living cell features such as compartmentalization of enzymatic reactions and responsiveness to external stimuli. This provides novel design ideas for the construction of artificial cells. This paper aims to explore the construction and application of biogenic drug delivery systems based on whole cells, cell membrane-encapsulated nanoparticles, exosomes, bacteria, bacterial outer membrane vesicles and artificial cells, taking into account recent advances in this field. The advantages and limitations of current synthetic biology-based nanodrug delivery systems for clinical translation are discussed, and the future prospects of nanotechnology for intelligent drug diagnostic and therapeutic systems are envisioned.
Non-alcoholic fatty liver disease (NAFLD) is prevalent worldwide as a chronic liver disease that not only gives rise to hepatic complications, but leads to other chronic diseases such as type 2 diabetes and atherosclerosis. The aberrant accumulation of lipid droplets (LDs) in hepatocytes is a prominent signature of NAFLD. However, conventional techniques lack the capability to effectively monitor the dynamic changes in LD levels during NAFLD with living organisms. Hence, it is imperative to develop LD-specific long-wavelength fluorescent probes with high imaging contrast for the in-situ diagnosis of NAFLD. In this study, we synthesized a new LD-selective long-wavelength fluorescent probe, denoted as LD-1, based on the twisted intramolecular charge transfer (TICT) mechanism. The probe exhibits a large Stokes shift and intensive fluorescence emission in nonpolar and viscous solutions. By self-assembling LD-1 with bovine serum albumin (BSA), a biocompatible, long-wavelength fluorescent probe hybrid, LD-1@BSA, was formed, allowing for LDs to be selectively imaged in hepatocytes. Moreover, LD-1@BSA successfully discriminates NAFLD cells before and after drug treatment, and achieves non-invasive and real-time monitoring of LD accumulation in a mouse model of NAFLD.
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