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学者姓名：李婧影
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Abstract ：
Abnormal tumor microenvironment imposes barriers to tumor penetration of nanomedicine, which remains a major challenge for effective anti-tumor. Herein, we present disulfide-based nanoparticles that actively penetrate deep tumors in vivo through a thiol-mediated transportation pathway. To achieve active tumor accumulation in vivo, disulfide-based nanoparticles are modified with folic acid units (FA-DBNPs). It is gratifying that FA-DBNPs still enter cells via the thiol-mediated pathway, which facilitates transcellular transportation and tumor penetration both in vitro and in vivo. Besides, FA-DBNPs exhibit GSH concentration-dependent depolymerization characterization, indicating that the GSH level in tumor tissues regulates the penetration depth of FA-DBNPs. Benefiting from these advantages, FA-DBNPs showed potent anti-tumor activity in mouse models, leading to the significant regression of tumors. The current study lays a foundation that thiol-mediated transportation is a promising approach in nanomedicine design for solid tumor therapy.
Keyword ：
deep penetration deep penetration solid tumor solid tumor thiol-mediated pathway thiol-mediated pathway transcellular transportation transcellular transportation
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| GB/T 7714 | Zhang, Junjie , Sun, Weican , Wang, Xing et al. Thiol-mediated transportation pathway: an approach for improving tumor penetration of nanomedicines in vivo [J]. | SCIENCE CHINA-CHEMISTRY , 2024 , 67 (1) : 383-389 . |
| MLA | Zhang, Junjie et al. "Thiol-mediated transportation pathway: an approach for improving tumor penetration of nanomedicines in vivo" . | SCIENCE CHINA-CHEMISTRY 67 . 1 (2024) : 383-389 . |
| APA | Zhang, Junjie , Sun, Weican , Wang, Xing , Chen, Senyan , Li, Jingying , Yang, Huanghao . Thiol-mediated transportation pathway: an approach for improving tumor penetration of nanomedicines in vivo . | SCIENCE CHINA-CHEMISTRY , 2024 , 67 (1) , 383-389 . |
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Retinal diseases, such as age-related macular degeneration, diabetic retinopathy, and retinoblastoma, stand as the leading causes of irreversible vision impairment and blindness worldwide. Effectively administering drugs for retinal diseases poses a formidable challenge due to the presence of complex ocular barriers and elimination mechanisms. Over time, various approaches have been developed to fabricate drug delivery systems for improving retinal therapy including virus vectors, lipid nanoparticles, and polymers. However, conventional nanocarriers encounter issues related to the controllability, efficiency, and safety in the retina. Therefore, the development of smart nanocarriers for effective or more invasive long-term treatment remains a desirable goal. Recently, approaches have surfaced for the intelligent design of nanocarriers, leveraging specific responses to external or internal triggers and enabling multiple functions for retinal therapy such as topical administration, prolonged drug release, and site-specific drug delivery. This Review provides an overview of prevalent retinal pathologies and related pharmacotherapies to enhance the understanding of retinal diseases. It also surveys recent developments and strategies employed in the intelligent design of nanocarriers for retinal disease. Finally, the challenges of smart nanocarriers in potential clinical retinal therapeutic applications are discussed to inspire the next generation of smart nanocarriers.
Keyword ：
ophthalmology ophthalmology posteriorsegment drug delivery posteriorsegment drug delivery retinal disease retinal disease smart nanocarriers smart nanocarriers stimuli-response stimuli-response
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| GB/T 7714 | Liu, Shuya , Yan, Zhike , Huang, Zixiang et al. Smart Nanocarriers for the Treatment of Retinal Diseases [J]. | ACS APPLIED BIO MATERIALS , 2024 , 7 (4) : 2070-2085 . |
| MLA | Liu, Shuya et al. "Smart Nanocarriers for the Treatment of Retinal Diseases" . | ACS APPLIED BIO MATERIALS 7 . 4 (2024) : 2070-2085 . |
| APA | Liu, Shuya , Yan, Zhike , Huang, Zixiang , Yang, Huanghao , Li, Jingying . Smart Nanocarriers for the Treatment of Retinal Diseases . | ACS APPLIED BIO MATERIALS , 2024 , 7 (4) , 2070-2085 . |
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The complexity of genetic circuits has not seen a significant increase over the last decades, even with the rapid development of synthetic biology tools. One of the bottlenecks is the limited number of orthogonal transcription factor-operator pairs. Researchers have tried to use aptamer-ligand pairs as genetic parts to regulate transcription. However, most aptamers selected using traditional methods cannot be directly applied in gene circuits for transcriptional regulation. To that end, we report a new method called CIVT-SELEX to select DNA aptamers that can not only bind to macromolecule ligands but also undergo significant conformational changes, thus affecting transcription. The single-stranded DNA library with affinity to our example ligand human thrombin protein is first selected and enriched. Then, these ssDNAs are inserted into a genetic circuit and tested in the in vitro transcription screening to obtain the ones with significant inhibitory effects on downstream gene transcription when thrombins are present. These aptamer-thrombin pairs can inhibit the transcription of downstream genes, demonstrating the feasibility and robustness of their use as genetic parts in both linear DNAs and plasmids. We believe that this method can be applied to select aptamers of any target ligands and vastly expand the genetic part library for transcriptional regulation.
Keyword ：
aptamer aptamer CIVT-SELEX CIVT-SELEX genetic part genetic part synthetic biology synthetic biology thrombin thrombin transcriptional regulation transcriptional regulation
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| GB/T 7714 | Guo, Shaobin , Xu, Zeqi , Lin, Lujie et al. Using CIVT-SELEX to Select Aptamers as Genetic Parts to Regulate Gene Circuits in a Cell-Free System [J]. | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES , 2023 , 24 (3) . |
| MLA | Guo, Shaobin et al. "Using CIVT-SELEX to Select Aptamers as Genetic Parts to Regulate Gene Circuits in a Cell-Free System" . | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 24 . 3 (2023) . |
| APA | Guo, Shaobin , Xu, Zeqi , Lin, Lujie , Guo, Yan , Li, Jingying , Lu, Chunhua et al. Using CIVT-SELEX to Select Aptamers as Genetic Parts to Regulate Gene Circuits in a Cell-Free System . | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES , 2023 , 24 (3) . |
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We developed a circular bivalent aptamer (CBA) to precisely activate membrane receptor-mediated regenerative signaling for liver repair in vivo. The CBA showed enhanced biostability and receptor binding avidity, achieving effective pathway activation and satisfactory treatment in an acetaminophen-induced liver injury model. This work expands aptamer-based molecular engineering in regenerative medicine.
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| GB/T 7714 | Liang, Hong , Yan, Zhike , Tong, Yuhong et al. Circular bivalent aptamers enhance the activation of the regenerative signaling pathway for repairing liver injury in vivo [J]. | CHEMICAL COMMUNICATIONS , 2023 , 59 (12) : 1621-1624 . |
| MLA | Liang, Hong et al. "Circular bivalent aptamers enhance the activation of the regenerative signaling pathway for repairing liver injury in vivo" . | CHEMICAL COMMUNICATIONS 59 . 12 (2023) : 1621-1624 . |
| APA | Liang, Hong , Yan, Zhike , Tong, Yuhong , Chen, Shan , Li, Jingying , Chen, Lanlan et al. Circular bivalent aptamers enhance the activation of the regenerative signaling pathway for repairing liver injury in vivo . | CHEMICAL COMMUNICATIONS , 2023 , 59 (12) , 1621-1624 . |
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Transmembrane proteins (TMEMs) are integrated membrane proteins that span the entire lipid bilayer and are permanently anchored to it. TMEMs participate in various cellular processes. Some TMEMs usually exist and perform their physiological functions as dimers rather than monomers. TMEM dimerization is associated with various physiological functions, such as the regulation of enzyme activity, signal transduction, and cancer immunotherapy. In this review, we focus on the dimerization of transmembrane proteins in cancer immunotherapy. This review is divided into three parts. First, the structures and functions of several TMEMs related to tumor immunity are introduced. Second, the characteristics and functions of several typical TMEM dimerization processes are analyzed. Finally, the application of the regulation of TMEM dimerization in cancer immunotherapy is introduced.
Keyword ：
cancer immunotherapy cancer immunotherapy dimerization dimerization dimerization regulation dimerization regulation small-molecule drugs small-molecule drugs transmembrane proteins transmembrane proteins
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| GB/T 7714 | Li, Lei , Li, Jingying . Dimerization of Transmembrane Proteins in Cancer Immunotherapy [J]. | MEMBRANES , 2023 , 13 (4) . |
| MLA | Li, Lei et al. "Dimerization of Transmembrane Proteins in Cancer Immunotherapy" . | MEMBRANES 13 . 4 (2023) . |
| APA | Li, Lei , Li, Jingying . Dimerization of Transmembrane Proteins in Cancer Immunotherapy . | MEMBRANES , 2023 , 13 (4) . |
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The first approved RNAi therapeutics, ONPATTRO, in 2017 moves the concept of RNA interference (RNAi) therapy from research to clinical reality, raising the hopes for the treatment of currently incurable diseases. However, RNAi therapeutics are still facing two main challenges-susceptibility to enzymatic degradation and low ability to escape from endo/lysosome into the cytoplasm. Therefore, we developed disulfide-based nanospheres (DBNPs) as universal vehicles to achieve efficient RNA delivery to address these problems. Notably, the DBNPs possess unique and desirable features, including improved resistance to nuclease degradation, direct cytoplasmic delivery through thiol-mediated cellular uptake, and cytosolic environment-responsive release, greatly enhancing the bioavailability of RNA therapeutics. Additionally, DBNPs are superior in terms of overcoming formidable physiological barriers, including vascular barriers and impermeable tumor tissues. Owning to these advantages, the DBNPs exhibit efficient gene silencing effect when delivering either small interfering RNA (siRNA) or microRNA in various cell lines and gener-ate remarkable growth inhibition in the zebrafish and mouse model of pancreatic tumors as compared to traditional delivery vectors, such as PEI. Therefore, DBNPs have potential application prospect in RNAi therapy both in vitro and in vivo.
Keyword ：
Cytoplasmic delivery Cytoplasmic delivery Gene silencing Gene silencing Pancreatic tumor Pancreatic tumor RNAi therapeutics RNAi therapeutics Thiol-mediated uptake Thiol-mediated uptake Tumor permeability Tumor permeability Vascular penetration Vascular penetration Zebrafish Zebrafish
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| GB/T 7714 | Zhou, Jie , Zhang, Junjie , Chen, Senyan et al. Full length article Direct cytoplasmic delivery of RNAi therapeutics through a non-lysosomal pathway for enhanced gene therapy [J]. | ACTA BIOMATERIALIA , 2023 , 170 : 401-414 . |
| MLA | Zhou, Jie et al. "Full length article Direct cytoplasmic delivery of RNAi therapeutics through a non-lysosomal pathway for enhanced gene therapy" . | ACTA BIOMATERIALIA 170 (2023) : 401-414 . |
| APA | Zhou, Jie , Zhang, Junjie , Chen, Senyan , Lin, Qinghua , Zhu, Rong , Wang, Liping et al. Full length article Direct cytoplasmic delivery of RNAi therapeutics through a non-lysosomal pathway for enhanced gene therapy . | ACTA BIOMATERIALIA , 2023 , 170 , 401-414 . |
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Current therapeutic strategies for Alzheimer's disease (AD) mainly focus on amyloid beta oligomer (A beta O) formation or clearance. However, most of them have failed to yield good clinical results. There is an urgent need to explore an alternative therapeutic target for AD treatments. Recent studies have indicated that the cellular prion protein (PrPC) is one of the cell-surface receptors of A beta O that mediates related neurotoxicity. Besides, as a neuroprotective protein, the dimerization of PrPC seems to be critical for its trophic activity. We presume that modulating PrPC receptor activity could be another potential approach to abrogate A beta O toxicity. In the present work, using an aptamer-induced dimerization (AID) strategy, we enforce PrPC dimerization and modulate its neurotrophic signaling. The AID strategy can attenuate A beta O toxic action by (i) interfering with A beta O-PrPC interaction and promoting neuroprotective shedding of PrPC; (ii) preventing the A beta O-induced mitochondrial dysfunction and the caspase-3-induced apoptosis; and (iii) reducing the secretion of inflammatory cytokines and relieving the neuroinflammation microenvironment. Our findings suggest that the strategy targeting PrPC signaling may shed light on validating new therapeutic strategies in AD.
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| GB/T 7714 | Liu, Shuya , Li, Shiwei , Lin, Jirong et al. Aptamer-Induced-Dimerization Strategy Attenuates A beta O Toxicity through Modulating the Trophic Activity of PrPC Signaling [J]. | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 2022 . |
| MLA | Liu, Shuya et al. "Aptamer-Induced-Dimerization Strategy Attenuates A beta O Toxicity through Modulating the Trophic Activity of PrPC Signaling" . | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2022) . |
| APA | Liu, Shuya , Li, Shiwei , Lin, Jirong , Li, Jingying , Yang, Huanghao . Aptamer-Induced-Dimerization Strategy Attenuates A beta O Toxicity through Modulating the Trophic Activity of PrPC Signaling . | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 2022 . |
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Systematic interrogation of correlative signaling components in their native environment is of great interest for dissecting sophisticated cellular signaling. However, it remains a challenge because of the lack of versatile and effective approaches. Herein, we propose a cell membrane-anchored DNA multitasking processor acting as a "traffic light" for integrated analyses of cellular signal transduction. Enhanced and controllable inhibition of c-Met signaling was achieved by membrane-anchoring of DNA processors. Moreover, the multitasking capability of the DNA processor allowed the monitoring of correlative VEGF secretion induced by c-Met activity regulation directly. By exploiting versatile aptameric nucleic acids, this modular designed DNA multitasking processor dissected how cell surface receptors coordinated with related components in live cells systematically. Therefore, it provides a powerful chemical tool for both fundamental cell biology research and precision medicine applications.
Keyword ：
Aptamers Aptamers Cellular Signaling Cellular Signaling Membrane Anchoring Membrane Anchoring Multitasking Processor Multitasking Processor Photo-Control Photo-Control
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| GB/T 7714 | Chen, Shan , Xu, Zhifei , Li, Shiwei et al. Systematic Interrogation of Cellular Signaling in Live Cells Using a Membrane-Anchored DNA Multitasking Processor [J]. | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION , 2022 , 61 (11) . |
| MLA | Chen, Shan et al. "Systematic Interrogation of Cellular Signaling in Live Cells Using a Membrane-Anchored DNA Multitasking Processor" . | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 61 . 11 (2022) . |
| APA | Chen, Shan , Xu, Zhifei , Li, Shiwei , Liang, Hong , Zhang, Chen , Wang, Zonghua et al. Systematic Interrogation of Cellular Signaling in Live Cells Using a Membrane-Anchored DNA Multitasking Processor . | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION , 2022 , 61 (11) . |
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Abstract ：
蛋白质是参与各种生理过程的关键生物分子。选择性的蛋白质化学修饰为开发新型生物制药和复杂生物系统中单个蛋白质的功能研究提供了有力工具。核酸作为一种多功能的分子工具，近十年被广泛用于构建选择性的蛋白质修饰策略。在这类策略中，核酸可以：（i）作为模板来辅助反应基团与蛋白质靠近，提高有效反应浓度；（ii）作为导向系统通过结合兴趣蛋白（Proteins of interest,POI）实现共价修饰的选择性；（iii）作为催化剂增强邻近区域的蛋白质修饰反应。该综述着重介绍核酸介导蛋白质共价标记策略的研究进展，并以不同的导向系统为分类，介绍了这类标记策略的发展及主要应用。
Keyword ：
核酸 核酸 蛋白质 蛋白质 选择性共价修饰 选择性共价修饰
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| GB/T 7714 | 杨雯 , 李婧影 , 杨黄浩 . 核酸介导蛋白质共价修饰的研究进展 [J]. | 分析测试学报 , 2022 , 41 (09) : 1395-1402 . |
| MLA | 杨雯 et al. "核酸介导蛋白质共价修饰的研究进展" . | 分析测试学报 41 . 09 (2022) : 1395-1402 . |
| APA | 杨雯 , 李婧影 , 杨黄浩 . 核酸介导蛋白质共价修饰的研究进展 . | 分析测试学报 , 2022 , 41 (09) , 1395-1402 . |
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The protein nanoenvironment on the plasma membrane is intimately linked to cellular biological functions. Elucidation of the protein nanoenvironment contributes to understanding the pathological mechanism and discovery of disease biomarkers. However, methods enabling characterization of the protein nanoenvironment in the endogenous biological environment have been rarely developed. Toward this end, we created a nucleic acid tool called AptGq/h for proximity labeling to decipher the endogenous protein nanoenvironment. Here, the aptamer acts as an anchor for binding the protein of interest (POI). The G-quadruplex/hemin complex induces proximity labeling of POI via catalyzing the conversion of inert small-molecule substrates into short-lived reactive species. The labeled proteins enable the subsequent affinity-based enrichment and proteomic analysis. We first characterized Apt-Gq/h-mediated POI labeling in vitro and tested its utility by interrogating the protein nanoenvironment of POI in living cells. Taking advantage of the nongenetic, multiple reaction sites, and rapid proximity labeling, Apt-Gq/h was further utilized to imaging the cell-cell connection and amplification detection of biomarkers in living cells and tissue sections. We believe that Apt-Gq/h will be a potential tool for basic science and clinical applications.
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| GB/T 7714 | Yang, Wen , Huang, Zixiang , Xu, Zhifei et al. Selective and Nongenetic Peroxidase Tag of Membrane Protein: a Nucleic Acid Tool for Proximity Labeling [J]. | ANALYTICAL CHEMISTRY , 2021 , 94 (2) : 1101-1107 . |
| MLA | Yang, Wen et al. "Selective and Nongenetic Peroxidase Tag of Membrane Protein: a Nucleic Acid Tool for Proximity Labeling" . | ANALYTICAL CHEMISTRY 94 . 2 (2021) : 1101-1107 . |
| APA | Yang, Wen , Huang, Zixiang , Xu, Zhifei , Ma, Xin , Huang, Shan , Li, Jingying et al. Selective and Nongenetic Peroxidase Tag of Membrane Protein: a Nucleic Acid Tool for Proximity Labeling . | ANALYTICAL CHEMISTRY , 2021 , 94 (2) , 1101-1107 . |
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