nanomaterials and their application in the biomedicine. [7] Indeed, over the past decades, formation of protein corona onto surfaces of NPs has attracted great attentions in the nanotechnology and biology community, and impressive progress has been achieved. [8,9] Nevertheless, a quantitative analysis on the formation process of the protein corona is very difficult and complicated, owing to the highly dynamic NP-protein interaction process and too many influencing factors.Among various types of nanomaterials, ultrasmall NPs with sizes smaller than 10 nm (i.e., quantum dots, [10] metal nanoclusters, [11] and carbon dots) [12] show unique properties and great potential in molecular imaging for disease diagnosis and cancer treatment. Particularly, compared with large NPs, these ultrasmall NPs can more readily escape from macrophages, pass biological barriers, show longer blood circulation times, and be easily degraded or excreted in the living systems. [13,14] Thus, these ultrasmall NPs have been widely employed in various biomedical applications. However, a deep and comprehensive understanding of their biological behavior, i.e., NP-protein interactions, remains largely unclear yet mainly due to the lack of appropriate in situ characterization tools for these ultrasmall NPs. While researchers have developed several techniques such as fluorescence correlation spectroscopy, [15] dynamic light scattering, [16] synchrotron radiation-based techniques, [17] and nuclear magnetic resonance spectroscopy [18] enabling quantitative analysis of protein corona, it still requires the development of new approaches to monitor the protein-NP interactions in a highly sensitive and quantitative manner owing to the diversity of nanomaterials and complexity of biological systems. [19] Fluorescence resonance energy transfer (FRET) is the process of nonradiative transmission of excitation energy from an excited state donor to a ground state acceptor, resulting from the dipole-dipole interactions. [20] The efficiency of this energy transfer process is inversely proportional to the sixth power of the distance between donor and acceptor, making FRET extremely sensitive to small changes in distance. Therefore, FRET has been widely exploited as a "spectroscopic ruler" in many biological and biophysical researches. For example, FRET can be employed for monitoring conformational changes of biomolecules, [21] developing highly sensitive fluorescence A fundamental understanding of nanoparticle-protein corona and its interactions with biological systems is essential for future application of engineered nanomaterials. In this work, fluorescence resonance energy transfer (FRET) is employed for studying the protein adsorption behavior of nanoparticles. The adsorption of human serum albumin (HSA) onto the surface of InP@ZnS quantum dots (QDs) with different chirality (dand l-penicillamine) shows strong discernible differences in the binding behaviors including affinity and adsorption orientation that are obtained upon quantitative analysis of FRET data...
Gold nanoclusters (AuNCs) represent an emerging type of engineered nanomaterials with intrinsic enzymatic activity for both chemical and biological applications, but the catalytic activity of most reported AuNCs remains rather limited. Herein, we report a new, efficient strategy of promoting the peroxidase-mimic activity of AuNCs by tailoring their catalytic interfaces via small molecule-mediated weak interactions. Inspired by the presence of imidazole structures in many biocatalytic centers, we screened a series of imidazole-containing small molecules to evaluate their impact on the enzymatic activity of AuNCs. Through monitoring the absorbance change of 3,3′,5,5′-tetramethylbenzidine, 1-methyl-2-imidazolecarboxaldehyde (MCA) was identified to possess the most significant effect on enhancing the peroxidase-mimic activity of glutathione-stabilized AuNCs (GSH-AuNCs) among all the examined molecules. Interestingly, the enhancement effect of MCA on the catalytic activity of these AuNCs was found to be highly reversible and can be switched on/off by simply adding MCA/dialysis treatment. Molecular dynamics simulations and further experimental analysis confirmed that these MCA molecules were adsorbed on the surface of GSH-AuNCs through weak non-covalent interactions. The underlying mechanism analysis suggested that the presence of MCA can efficiently promote the production of •OH in the GSH-AuNC system. As a proof of example, we then demonstrated that the presence of MCA can greatly increase the bioanalytical performance of AuNC-based peroxidase mimics, as evidenced by a 65-fold lower LOD for glucose detection of AuNCs@MCA than that using AuNCs only. Finally, the present system has been successfully applied for sensing the blood glucose level of both healthy people and diabetics with promising results.
Metal aerogels represent an emerging type of functional porous materials with promising applications in diverse fields, but the fabrication of metal aerogels with specific structure and property still remains a challenge. Here, the authors report a new approach to fabricate metal aerogels by using ultrasmall metal nanoclusters (NCs) as functional building blocks. By taking D‐penicillamine‐stabilized gold NCs (AuNCs) with a diameter of 1.4 nm as an example, Au aerogels with ultrafine ligament size (3.5 nm) and good enzyme‐mimic properties are synthesized. Detailed characterization shows that the obtained Au aerogels possess typical 3D self‐supported porous network structure with high gold purity and surface area. Time‐lapse spectroscopic and microscopic monitoring of the gelation process reveal that these ultrasmall AuNCs first grow into large nanoparticles before fusion into nanowire networks, during which both pH and the precursor concentration are identified to be the determining factor. Owing to their highly porous structure and abundant metal nodes, these self‐supported Au aerogels display excellent peroxidase‐like properties. This work provides a strategy for fabricating advanced metal aerogels by taking ultrasmall‐sized metal NCs as building blocks, which also opens new avenues for engineering the structure and properties of metal aerogels for further advancing their applications.
IntroductionHigh-grade serous ovarian cancer (HGSOC) is the most common histological subtype of ovarian cancer, and is associated with high mortality rates.MethodsIn this study, we analyzed specific cell subpopulations and compared different gene functions between healthy ovarian and ovarian cancer cells using single-cell RNA sequencing (ScRNA-seq). We delved deeper into the differences between healthy ovarian and ovarian cancer cells at different levels, and performed specific analysis on endothelial cells.ResultsWe obtained scRNA-seq data of 6867 and 17056 cells from healthy ovarian samples and ovarian cancer samples, respectively. The transcriptional profiles of the groups differed at various stages of ovarian cell development. A detailed comparison of the cell cycle, and cell communication of different groups, revealed significant differences between healthy ovarian and ovarian cancer cells. We also found that apoptosis-related genes, URI1, PAK2, PARP1, CLU and TIMP3, were highly expressed, while immune-related genes, UBB, RPL11, CAV1, NUPR1 and Hsp90ab1, were lowly expressed in ovarian cancer cells. The results of the ScRNA-seq were verified using qPCR.DiscussionOur findings revealed differences in function, gene expression and cell interaction patterns between ovarian cancer and healthy ovarian cell populations. These findings provide key insights on further research into the treatment of ovarian cancer.
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