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学者姓名：杨黄浩
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Abstract ：
Proteolysis-targeting chimeras (PROTACs) are dual-functional molecules composed of a protein of interest (POI) ligand and an E3 ligase ligand connected by a linker, which can recruit POI and E3 ligases simultaneously, thereby inducing the degradation of POI and showing great potential in disease treatment. A challenge in developing PROTACs is the design of linkers and the modification of ligands to establish a multifunctional platform that enhances degradation efficiency and antitumor activity. As a programmable and modifiable nanomaterial, DNA tetrahedron can precisely assemble and selectively recognize molecules and flexibly adjust the distance between molecules, making them ideal linkers. Herein, we developed a multivalent PROTAC based on a DNA tetrahedron, named AS-TD2-PRO. Using DNA tetrahedron as a linker, we combined modules targeting tumor cells, recognizing E3 ligases, and multiple POI together. We took the undruggable target protein signal transducer and activator of transcription 3 (STAT3), associated with the etiology and progression in a variety of malignant tumors, as an example in this study. AS-TD2-PRO with two STAT3 recognition modules demonstrated good potential in enhancing tumor-specific targeting and degradation efficiency compared to traditional bivalent PROTACs. Furthermore, in a mouse tumor model, the superior therapeutic activity of AS-TD2-PRO was observed. Overall, DNA tetrahedron-driven multivalent PROTACs both serve as a proof of principle for multifunctional PROTAC design and introduce a promising avenue for cancer treatment strategies.
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| GB/T 7714 | Li, Shiqing , Zeng, Tao , Wu, Zhixing et al. DNA Tetrahedron-Driven Multivalent Proteolysis-Targeting Chimeras: Enhancing Protein Degradation Efficiency and Tumor Targeting [J]. | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 2025 , 147 (2) : 2168-2181 . |
| MLA | Li, Shiqing et al. "DNA Tetrahedron-Driven Multivalent Proteolysis-Targeting Chimeras: Enhancing Protein Degradation Efficiency and Tumor Targeting" . | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 147 . 2 (2025) : 2168-2181 . |
| APA | Li, Shiqing , Zeng, Tao , Wu, Zhixing , Huang, Jiabao , Cao, Xiuping , Liu, Yana et al. DNA Tetrahedron-Driven Multivalent Proteolysis-Targeting Chimeras: Enhancing Protein Degradation Efficiency and Tumor Targeting . | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 2025 , 147 (2) , 2168-2181 . |
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Evaluating tumor radiosensitivity is beneficial for the prediction of treatment efficacy, customization of treatment plans, and minimization of side effects. Tracking the mitochondrial DNA (mtDNA) repair process helps to assess tumor radiosensitivity as mtDNA repair determines the fate of the cell under radiation-induced mtDNA damage. However, current probes developed to monitor levels of DNA repair enzymes suffered from complex synthesis, uncontrollable preparation, limited tumor selectivity, and poor organelle-targeting ability. Especially, the correlation between mtDNA repair activity and inherent radiosensitivity of tumors has not yet been explored. Here, we present a mitochondria-targeted DNA-based nanoprobe (TPP-Apt-tFNA) for in situ monitoring of the activity of the mtDNA repair enzyme and evaluating tumor radiosensitivity. TPP-Apt-tFNA consists of a DNA tetrahedral framework precisely modified with three functional modules on each of the three vertexes, that is, the tumor cell-targeting aptamer, the mitochondrion-targeting moiety, and the apurinic/apyrimidinic endonuclease 1 (APE1)-responsive molecule beacon. Once selectively internalized by tumor cells, the nanoprobe targeted the mitochondrion and specifically recognized APE1 to activate fluorescence, allowing the observation of mtDNA repair activity. The nanoprobe showed elevated APE1 levels in the mitochondria of tumor cells under oxidative stress. Moreover, the nanoprobe enabled the illumination of different levels of APE1-mediated mtDNA repair activity in different cell cycle phases. Furthermore, using the nanoprobe in vitro and in vivo, we found that tumor cells with high activity of mtDNA repair, which allowed them to recover from radiation-induced mtDNA lesions, had low sensitivity to radiation and an unsatisfactory radiotherapy outcome. Our work provides a new imaging tool for exploring the roles of mtDNA repair activity in diverse biological processes and for guiding tumor radiation treatment.
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| GB/T 7714 | Chen, Lanlan , Lai, Jingjing , Dong, Siqi et al. Mitochondria-Targeted DNA-Based Nanoprobe for In Situ Monitoring of the Activity of the mtDNA Repair Enzyme and Evaluating Tumor Radiosensitivity [J]. | ANALYTICAL CHEMISTRY , 2025 , 97 (1) : 382-391 . |
| MLA | Chen, Lanlan et al. "Mitochondria-Targeted DNA-Based Nanoprobe for In Situ Monitoring of the Activity of the mtDNA Repair Enzyme and Evaluating Tumor Radiosensitivity" . | ANALYTICAL CHEMISTRY 97 . 1 (2025) : 382-391 . |
| APA | Chen, Lanlan , Lai, Jingjing , Dong, Siqi , Liu, Wenjun , Zhang, Ximei , Yang, Huanghao . Mitochondria-Targeted DNA-Based Nanoprobe for In Situ Monitoring of the Activity of the mtDNA Repair Enzyme and Evaluating Tumor Radiosensitivity . | ANALYTICAL CHEMISTRY , 2025 , 97 (1) , 382-391 . |
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The development of RNA interference (RNAi) therapy offers a potential solution for Alzheimer's disease (AD). However, the brain-blood barrier (BBB) with its selective permeability and pharmacokinetic-related challenges poses restrictions on the delivery of small interfering RNA (siRNA) to the central nervous system (CNS). In this study, we demonstrate that the incorporation of 2 '-fluoro (2 '-F) substitutions and L-carnitine modification facilitates the self-assembly of siRNA through triple interaction, leading to the formation of nanorings, called LCSF-NR. Based on the enhanced cellular uptake and lysosomal escape by 2 '-F substitution and the transport across the BBB promoted by L-carnitine, the nanorings realized the improved brain-targeted delivery of siRNA, both in zebrafish and mice models. Moreover, our findings highlight the therapeutic potential of LCSF-NR formulation in an AD zebrafish model through a synergistic effect of downregulating the beta-site APP cleavage enzyme 1 (BACE1) gene and L-carnitine-mediated neuroprotection, effectively inhibiting pathological processes. Overall, these results suggest that the chemical modification-based siRNA self-assembly strategy enables trans-BBB delivery and presents a concise approach for synergistic therapy of AD.
Keyword ：
Alzheimer's disease Alzheimer's disease blood-brain barrier blood-brain barrier chemical modification chemical modification self-assembly self-assembly siRNA siRNA
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| GB/T 7714 | Jiang, Yifan , Li, Lisha , Fang, Xiao et al. Self-assembling chemically modified siRNA nanorings for RNAi therapy and neuroprotection in Alzheimer's disease [J]. | SCIENCE CHINA-CHEMISTRY , 2025 . |
| MLA | Jiang, Yifan et al. "Self-assembling chemically modified siRNA nanorings for RNAi therapy and neuroprotection in Alzheimer's disease" . | SCIENCE CHINA-CHEMISTRY (2025) . |
| APA | Jiang, Yifan , Li, Lisha , Fang, Xiao , Zeng, Tao , Su, Lichao , Liu, Yichang et al. Self-assembling chemically modified siRNA nanorings for RNAi therapy and neuroprotection in Alzheimer's disease . | SCIENCE CHINA-CHEMISTRY , 2025 . |
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Large osseous void, postsurgical neoplastic recurrence, and slow bone-cartilage repair rate raise an imperative need to develop functional scaffold in clinical osteosarcoma treatment. Herein, a bionic bilayer scaffold constituting croconaine dye-polyethylene glycol@sodium alginate hydrogel and poly(L-lactide)/hydroxyapatite polymer matrix is fabricated to simultaneously achieve a highly efficient killing of osteosarcoma and an accelerated osteochondral regeneration. First, biomimetic osteochondral structure along with adequate interfacial interaction of the bilayer scaffold provide a structural reinforcement for transverse osseointegration and osteochondral regeneration, as evidenced by upregulated specific expressions of collagen type-I, osteopontin, and runt-related transcription factor 2. Meanwhile, thermal ablation of the synthesized nanoparticles and mitochondrial dysfunction caused by continuously released hydroxyapatite induce residual tumor necrosis synergistically. To validate the capabilities of inhibiting tumor growth and promoting osteochondral regeneration of our proposed scaffold, a novel orthotopic osteosarcoma model simulating clinical treatment scenarios of bone tumors is established on rats. Based on amounts of in vitro and in vivo results, an effective killing of osteosarcoma and a suitable osteal-microenvironment modulation of such bionic bilayer composite scaffold are achieved, which provides insightful implications for photonic hyperthermia therapy against osteosarcoma and following osseous tissue regeneration.
Keyword ：
bilayer scaffold bilayer scaffold biomaterials biomaterials orthotopicosteosarcoma orthotopicosteosarcoma osteochondral regeneration osteochondral regeneration photonic hyperthermiatherapy photonic hyperthermiatherapy
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| GB/T 7714 | Gong, Chenchi , Wang, Jun , Tang, Faqiang et al. Bionic Bilayer Scaffold for Synchronous Hyperthermia Therapy of Orthotopic Osteosarcoma and Osteochondral Regeneration [J]. | ACS APPLIED MATERIALS & INTERFACES , 2024 , 16 (7) : 8538-8553 . |
| MLA | Gong, Chenchi et al. "Bionic Bilayer Scaffold for Synchronous Hyperthermia Therapy of Orthotopic Osteosarcoma and Osteochondral Regeneration" . | ACS APPLIED MATERIALS & INTERFACES 16 . 7 (2024) : 8538-8553 . |
| APA | Gong, Chenchi , Wang, Jun , Tang, Faqiang , Tong, Dongmei , Wang, Ziyi , Zhou, Zijie et al. Bionic Bilayer Scaffold for Synchronous Hyperthermia Therapy of Orthotopic Osteosarcoma and Osteochondral Regeneration . | ACS APPLIED MATERIALS & INTERFACES , 2024 , 16 (7) , 8538-8553 . |
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Metal nanoclusters (MNCs) can be synthesized with atomically precise structures and molecule formulae due to the rapid development of nanocluster science in recent decades. The ultrasmall size range (normally < 2 nm) endows MNCs with plenty of molecular-like properties, among which photoluminescent properties have aroused extensive attention. Tracing the research and development processes of luminescent nanoclusters, various photoluminescent analysis and characterization methods play a significant role in elucidating luminescent mechanism and analyzing luminescent properties. In this review, it is aimed to systematically summarize the normally used photoluminescent characterizations in MNCs including basic parameters and methods, such as excitation/emission wavelength, quantum yield, and lifetime. For each key parameter, first its definition and meaning is introduced and then the relevant characterization methods including measuring principles and the revelation of luminescent properties from the collected data are discussed. Then, it is discussed in details how to explore the luminescent mechanism of MNCs and construct NC-based applications based on the measured data. By means of these characterization strategies, the luminescent properties of MNCs and NC-based designs can be explained quantitatively and qualitatively. Hence, this review is expected to provide clear guidance for researchers to characterize luminescent MNCs and better understand the luminescent mechanism from the measured results.
Keyword ：
luminescent properties luminescent properties metal nanoclusters metal nanoclusters photoluminescence photoluminescence photoluminescent characterization photoluminescent characterization photoluminescent lifetime photoluminescent lifetime
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| GB/T 7714 | Lin, Hongbin , Song, Xiaorong , Chai, Osburg Jin Huang et al. Photoluminescent Characterization of Metal Nanoclusters: Basic Parameters, Methods, and Applications [J]. | ADVANCED MATERIALS , 2024 , 36 (25) . |
| MLA | Lin, Hongbin et al. "Photoluminescent Characterization of Metal Nanoclusters: Basic Parameters, Methods, and Applications" . | ADVANCED MATERIALS 36 . 25 (2024) . |
| APA | Lin, Hongbin , Song, Xiaorong , Chai, Osburg Jin Huang , Yao, Qiaofeng , Yang, Huanghao , Xie, Jianping . Photoluminescent Characterization of Metal Nanoclusters: Basic Parameters, Methods, and Applications . | ADVANCED MATERIALS , 2024 , 36 (25) . |
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Long-lasting radioluminescence scintillators have recently attracted substantial attention from both research and industrial communities, primarily due to their distinctive capabilities of converting and storing X-ray energy. However, determination of energy-conversion kinetics in these nanocrystals remains unexplored. Here we present a strategy to probe and unveil energy-funneling kinetics in NaLuF4:Mn2+/Gd3+ nanocrystal sublattices through Gd3+-driven microenvironment engineering and Mn2+-mediated radioluminescence profiling. Our photophysical studies reveal effective control of energy-funneling kinetics and demonstrate the tunability of electron trap depth ranging from 0.66 to 0.96 eV, with the corresponding trap density varying between 2.38x105 and 1.34x107 cm-3. This enables controlled release of captured electrons over durations spanning from seconds to 30 days. It allows tailorable emission wavelength within the range of 520-580 nm and fine-tuning of thermally-stimulated temperature between 313-403 K. We further utilize these scintillators to fabricate high-density, large-area scintillation screens that exhibit a 6-fold improvement in X-ray sensitivity, 22 lp/mm high-resolution X-ray imaging, and a 30-day-long optical memory. This enables high-contrast imaging of injured mice through fast thermally-stimulated radioluminescence readout. These findings offer new insights into the correlation of radioluminescence dynamics with energy-funneling kinetics, thereby contributing to the advancement of high-energy nanophotonic applications. Energy-funneling kinetics in NaLuF4: Mn2+/Gd3+ nanocrystals were explored through precise microenvironment engineering within nanocrystal sublattices. The resulting tailorable radioluminescence afterglow enabled high-sensitivity, high-resolution X-ray imaging with an ultralong optical memory. image
Keyword ：
Electronic traps Electronic traps Energy funneling Energy funneling Nanocrystal scintillators Nanocrystal scintillators Radioluminescence afterglow Radioluminescence afterglow X-ray imaging X-ray imaging
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| GB/T 7714 | Wu, Qinxia , Xu, Xinqi , Li, Xiaokun et al. Probing Energy-Funneling Kinetics in Nanocrystal Sublattices for Superior X-Ray Imaging [J]. | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION , 2024 , 63 (25) . |
| MLA | Wu, Qinxia et al. "Probing Energy-Funneling Kinetics in Nanocrystal Sublattices for Superior X-Ray Imaging" . | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 63 . 25 (2024) . |
| APA | Wu, Qinxia , Xu, Xinqi , Li, Xiaokun , Jiang, Hao , Qin, Xian , Hong, Zhongzhu et al. Probing Energy-Funneling Kinetics in Nanocrystal Sublattices for Superior X-Ray Imaging . | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION , 2024 , 63 (25) . |
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Gold nanoclusters (AuNCs) are emerging as promising functional probes for bioapplications. However, because of rapid renal clearance, it is a challenge to tailor their biofate and improve their disease-targeting ability in vivo. Herein, we report an efficient strategy to tailor their organotropic actions by rationally designing AuNC assemblies. The nanocluster assembly is established based on the moderate electrostatic interaction or strong coordination between AuNCs, enabled by solely chitosan (CS) or the coadded chelating metal ions (e.g., Gd3+). We show that AuNCs-CS is rapidly excreted into urine, while further coordination of Gd3+ confers assemblies with liver and lung accumulation capabilities, dependent on Gd3+ contents. The organotropic actions are unraveled to result from their tunable stability in vivo and binding capability to cells/proteins. We also demonstrate that lung-targeting assemblies can enable specific NIR-II luminescence imaging of lung orthotopic tumors, which cannot be realized by employing discrete AuNCs. We anticipate that these findings will offer insights into the design principles of metal nanocluster probes and related bioapplications.
Keyword ：
gold clusters gold clusters in vivo imaging in vivo imaging luminescence imaging luminescence imaging metal nanoclusters metal nanoclusters nanoprobe nanoprobe
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| GB/T 7714 | Song, Xiaorong , Wei, Jing , Cai, Xiyang et al. Organotropic Engineering of Luminescent Gold Nanoclusters for In Vivo Imaging of Lung Orthotopic Tumors [J]. | ACS NANO , 2024 , 18 (49) : 33555-33565 . |
| MLA | Song, Xiaorong et al. "Organotropic Engineering of Luminescent Gold Nanoclusters for In Vivo Imaging of Lung Orthotopic Tumors" . | ACS NANO 18 . 49 (2024) : 33555-33565 . |
| APA | Song, Xiaorong , Wei, Jing , Cai, Xiyang , Liu, Yizhuo , Wu, Fengbo , Tong, Shufen et al. Organotropic Engineering of Luminescent Gold Nanoclusters for In Vivo Imaging of Lung Orthotopic Tumors . | ACS NANO , 2024 , 18 (49) , 33555-33565 . |
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X射线发光是指闪烁体在X射线激发下发射出低能量光子的过程，在生物传感、医学成像、光动力治疗、光遗传等领域具有应用前景。相较于传统的紫外激发光，X射线对生物组织具有高穿透性且不会触发生物体的自荧光，可实现深组织、无背景、高灵敏的生物分析。近年来，基于纳米闪烁体的X射线发光在生物光子学领域中得到广泛研究，促进了X射线发光在分析化学和生物医学中的应用。本文首先对闪烁体的X射线发光机理进行了概述，接着重点介绍了纳米闪烁体作为光学探针在生物分子测量与疾病治疗中的研究进展，包括生物传感、活体成像和光动力治疗等，最后讨论了该领域存在的一些挑战和可能的解决方案。
Keyword ：
X射线发光 X射线发光 光学探针 光学探针 生物分析 生物分析 纳米闪烁体 纳米闪烁体
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| GB/T 7714 | 徐新奇 , 张珍珍 , 陈小丰 et al. 基于纳米闪烁体的X射线发光生物分子测量与疾病治疗研究进展 [J]. | 化学通报 , 2024 , 87 (09) : 1009-1019 . |
| MLA | 徐新奇 et al. "基于纳米闪烁体的X射线发光生物分子测量与疾病治疗研究进展" . | 化学通报 87 . 09 (2024) : 1009-1019 . |
| APA | 徐新奇 , 张珍珍 , 陈小丰 , 陈秋水 , 杨黄浩 . 基于纳米闪烁体的X射线发光生物分子测量与疾病治疗研究进展 . | 化学通报 , 2024 , 87 (09) , 1009-1019 . |
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Mn-based metal halides scintillators with high photoluminescence quantum yield (PLQY) have recently emerged as promising large-size candidates for X-ray imaging but still remains as difficult challenge in stability and high processing temperatures. Here, three manganese halides are designed by introducing branched chains into organic cations and extending the carbon chains, namely (i-PrTPP)2MnBr4, (i-BuTPP)2MnBr4 and (i-AmTPP)2MnBr4, successfully lowered the melting point of manganese halides to 120.2 degrees C. Three materials show striking light yields of 59 000, 40 000, and 52 000 photons MeV-1, respectively. The lowest detection limits are 42.30, 50.92, and 45.71 nGy s-1, respectively. Meanwhile, compared to their counterparts with linear carbon chains, the introduction of branched chains has significantly enhanced the stability of the scintillators in the glass state. A transparent glass has been prepared using a melt-quenching method, which exhibited 80% transmittance at 400-700 nm. The glass is utilized for X-ray imaging, achieving a high spatial resolution up to 46.6 lp mm-1. This result provides a new approach to enhancing the performance of such scintillator materials.
Keyword ：
glass scintillator glass scintillator low temperature melting low temperature melting metal halide metal halide stability stability X-ray detection X-ray detection
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| GB/T 7714 | Chen, Shichuan , Guo, Cuiling , Chen, Shan-Ci et al. Enhanced Stability of Melt-Processable Organic-Inorganic Hybrid Manganese Halides for X-Ray Imaging [J]. | SMALL , 2024 , 20 (52) . |
| MLA | Chen, Shichuan et al. "Enhanced Stability of Melt-Processable Organic-Inorganic Hybrid Manganese Halides for X-Ray Imaging" . | SMALL 20 . 52 (2024) . |
| APA | Chen, Shichuan , Guo, Cuiling , Chen, Shan-Ci , Di, Yiming , Fang, Xin , Lin, Mei-Jin et al. Enhanced Stability of Melt-Processable Organic-Inorganic Hybrid Manganese Halides for X-Ray Imaging . | SMALL , 2024 , 20 (52) . |
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Nanovaccines have gathered significant attention for their potential to elicit tumor-specific immunological responses. Despite notable progress in tumor immunotherapy, nanovaccines still encounter considerable challenges such as low delivery efficiency, limited targeting ability, and suboptimal efficacy. With an aim of addressing these issues, engineering customized nanovaccines through modification or functionalization has emerged as a promising approach. These tailored nanovaccines not only enhance antigen presentation, but also effectively modulate immunosuppression within the tumor microenvironment. Specifically, they are distinguished by their diverse sizes, shapes, charges, structures, and unique physicochemical properties, along with targeting ligands. These features of nanovaccines facilitate lymph node accumulation and activation/regulation of immune cells. This overview of bespoke nanovaccines underscores their potential in both prophylactic and therapeutic applications, offering insights into their future development and role in cancer immunotherapy.
Keyword ：
Customized structure Customized structure Enhanced cancer immunotherapy Enhanced cancer immunotherapy Nanovaccines Nanovaccines Prophylactic and therapeutic applications Prophylactic and therapeutic applications Tailored-ligand Tailored-ligand
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| GB/T 7714 | Guo, Jinyu , Liu, Changhua , Qi, Zhaoyang et al. Engineering customized nanovaccines for enhanced cancer immunotherapy [J]. | BIOACTIVE MATERIALS , 2024 , 36 : 330-357 . |
| MLA | Guo, Jinyu et al. "Engineering customized nanovaccines for enhanced cancer immunotherapy" . | BIOACTIVE MATERIALS 36 (2024) : 330-357 . |
| APA | Guo, Jinyu , Liu, Changhua , Qi, Zhaoyang , Qiu, Ting , Zhang, Jin , Yang, Huanghao . Engineering customized nanovaccines for enhanced cancer immunotherapy . | BIOACTIVE MATERIALS , 2024 , 36 , 330-357 . |
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