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学者姓名：卢春华
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Abstract ：
Depression is one of the most common mental disorders. The inactivation of tryptophan hydroxylase and the resulting serotonin decrease are the key factors in depression pathology. Herein, we report for the first time that Fe3O4 nanoparticles exhibit tryptophan hydroxylase-like activity and successfully verify their ability to restore serotonin synthesis in the brain for the treatment of depression. To achieve better biocompatibility and brain delivery, the Fe3O4 nanoparticles were functionalized with chitosan (CS) (Fe3O4@CS), enabling their delivery from the nose to the brain. Fe3O4@CS catalyzes the transformation of tryptophan into 5-hydroxytryptophan with the participation of high levels of endogenous ascorbic acid and hydrogen peroxide in stressed neurons, thus compensating for the deactivated tryptophan hydroxylase in the brain. In vivo Fe3O4@CS treatment results in the recovery of 5-hydroxytryptophan and serotonin levels and improvement of neuronal signal transduction ability in a depression mouse model, thus ameliorating depressive-like behaviors. The presented strategy of restoring serotonin synthesis in situ based on a tryptophan hydroxylase-like nanozyme provides a more accurate and efficient approach for the treatment of depression.
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| GB/T 7714 | Fang, Xiao , Wu, Yue , Dai, Yaling et al. In Situ Recovery of Serotonin Synthesis by a Tryptophan Hydroxylase-Like Nanozyme for the Treatment of Depression [J]. | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 2025 , 147 (11) : 9111-9121 . |
| MLA | Fang, Xiao et al. "In Situ Recovery of Serotonin Synthesis by a Tryptophan Hydroxylase-Like Nanozyme for the Treatment of Depression" . | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 147 . 11 (2025) : 9111-9121 . |
| APA | Fang, Xiao , Wu, Yue , Dai, Yaling , Xiao, Han , Li, Shiqing , Chen, Xiaoning et al. In Situ Recovery of Serotonin Synthesis by a Tryptophan Hydroxylase-Like Nanozyme for the Treatment of Depression . | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 2025 , 147 (11) , 9111-9121 . |
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Photodynamic therapy (PDT) holds great promise for treating various types of cancer. However, its clinical advancement is hindered by the intrinsic hypoxic tumor microenvironment, which reduces PDT efficacy, and safety concerns related to the biological specificity of photosensitizers. Here we constructed a MnO2 nanosheet based DNA tetrahedron-photosensitizer (TMPyP4) nanoplatform (TPM), which integration with tumor targeting (aptamer), gene drugs (DNAzyme) and photosensitizer agents for enhanced PDT. Once the TPM entered cancer cells through aptamer targeting, the MnO2 nanosheet reacts with endogenous acidic and H2O2 to generate Mn2+ and oxygen (O2), thereby alleviating the tumor hypoxic. Subsequently, TMPyP4 further converts the generated O2 into singlet oxygen (1O2) under near-infrared light, enhancing PDT efficacy both in vitro and in vivo. Specifically, the generated Mn2+ activates the DNAzyme and accelerate tumor target mRNA cleavage, resulting in effective PDT-gene synergistic therapy for tumors. This work offers novel perspectives on advancing precise and highly effective gene-PDT systems.
Keyword ：
DNAzyme DNAzyme Gene therapy Gene therapy Hypoxic tumor microenvironment Hypoxic tumor microenvironment Metal cofactor Metal cofactor Photodynamic therapy Photodynamic therapy
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| GB/T 7714 | Zheng, Yanlin , Li, Fei , Zhu, Xiaohui et al. Multifunctional MnO2 nanosheet based DNA tetrahedron- photosensitizer nanoplatform for gene-photodynamic modulation [J]. | CHEMICAL ENGINEERING JOURNAL , 2025 , 505 . |
| MLA | Zheng, Yanlin et al. "Multifunctional MnO2 nanosheet based DNA tetrahedron- photosensitizer nanoplatform for gene-photodynamic modulation" . | CHEMICAL ENGINEERING JOURNAL 505 (2025) . |
| APA | Zheng, Yanlin , Li, Fei , Zhu, Xiaohui , Wang, Min , Wen, Yuantao , Zeng, Tao et al. Multifunctional MnO2 nanosheet based DNA tetrahedron- photosensitizer nanoplatform for gene-photodynamic modulation . | CHEMICAL ENGINEERING JOURNAL , 2025 , 505 . |
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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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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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RNA interference (RNAi) has been widely used in agriculture. However, it is well accepted that common methods of plant RNAi are species-dependent and lack systematic efficiency. This study designed a thiolated siRNA nanoparticle, guanidinium (Gu+)-containing disulfide assembled siRNA (Gu+-siRNA), demonstrating remarkable species independence and efficient systemic gene silencing across different plant species. Our results indicate that this approach effectively utilizes the plant vascular system to deliver siRNA, enabling long-distance gene silencing across both monocot and dicot plants, such as rice and Arabidopsis. By applying this method, we successfully targeted and silenced key genes like STM, WER, MYB23, GD1, EIL1, and EIL2, which regulate plant development and enhance salt tolerance. This delivery system significantly expands the application of RNAi technology across different plants, serving as a valuable tool for advancing agricultural biotechnology, enhancing crop resistance, and improving agricultural productivity, while aligning with global goals for sustainable food production and crop improvement.
Keyword ：
long-distance movement long-distance movement nanoparticle nanoparticle RNA interference RNA interference systematically deliver systematically deliver thiolated thiolated
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| GB/T 7714 | Lin, Shujin , Zhang, Qian , Bai, Shiyan et al. Beyond species and spatial boundaries: Enabling long-distance gene silencing in plants via guanidinium-siRNA nanoparticles [J]. | PLANT BIOTECHNOLOGY JOURNAL , 2025 , 23 (4) : 1165-1177 . |
| MLA | Lin, Shujin et al. "Beyond species and spatial boundaries: Enabling long-distance gene silencing in plants via guanidinium-siRNA nanoparticles" . | PLANT BIOTECHNOLOGY JOURNAL 23 . 4 (2025) : 1165-1177 . |
| APA | Lin, Shujin , Zhang, Qian , Bai, Shiyan , Yang, Liwen , Qin, Guannan , Wang, Liyuan et al. Beyond species and spatial boundaries: Enabling long-distance gene silencing in plants via guanidinium-siRNA nanoparticles . | PLANT BIOTECHNOLOGY JOURNAL , 2025 , 23 (4) , 1165-1177 . |
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The hypoxic tumor microenvironment (TME), inadequate penetration depth of Vis/NIR light, and lack of sustaining reactive oxygen species (ROS) production capability of photosensitizers pose significant obstacles to the widespread clinic applications of photodynamic therapy (PDT). Herein, we developed a "persistent type I X-PDT" platform to simultaneously overcome these three limitations. Such a nanoplatform could generate efficient ROS (center dot OH and O2 center dot-) under X-ray irradiation in both normoxic and hypoxic environments. The ROS production persists in tumor cells for more than 4 h, even after the X-ray source is removed. Notably, the persistent type I X-PDT does not increase the levels of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) in tumor cells both in vitro and in vivo. Moreover, to further enhance the radiotherapy efficacy in hypoxic conditions, a Pt (IV) prodrug was also introduced, which can be reduced to cisplatin selectively in tumor cells, functioning not only as a chemodrug but also as a radiosensitizer.
Keyword ：
chemotherapy chemotherapy hypoxia hypoxia persistent X-PDT persistent X-PDT radiation therapy radiation therapy type I ROS type I ROS
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| GB/T 7714 | Cheng, Wei , He, Shuai , Chen, Qiushui et al. X-ray Induced Persistent Type I Photodynamic Therapy with Enhanced Hypoxia Tolerance and Chemoradiotherapy [J]. | NANO LETTERS , 2025 , 25 (11) : 4549-4559 . |
| MLA | Cheng, Wei et al. "X-ray Induced Persistent Type I Photodynamic Therapy with Enhanced Hypoxia Tolerance and Chemoradiotherapy" . | NANO LETTERS 25 . 11 (2025) : 4549-4559 . |
| APA | Cheng, Wei , He, Shuai , Chen, Qiushui , Song, Xiaorong , Lu, Chunhua , Yang, Huanghao . X-ray Induced Persistent Type I Photodynamic Therapy with Enhanced Hypoxia Tolerance and Chemoradiotherapy . | NANO LETTERS , 2025 , 25 (11) , 4549-4559 . |
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Flap endonuclease 1 (FEN1) plays a vital role in cancer by modulating DNA repair mechanisms, inducing genomic instability, and serving as a promising biomarker for cancer diagnosis and prognosis. In this work, we present the development of a novel DNAzyme signal amplification-directed point-of-care sensing system (DzPGM) for the sensitive and specific detection of FEN1. The Dz-PGM system utilizes DNAzyme signal amplification in conjunction with a personal glucose meter (PGM) for reporting, capitalizing on a biochemical cascade initiated by FEN1 recognition. Benefiting from enzymatic recognition, magnetic separation, and DNAzyme based signal amplification, this Dz-PGM system demonstrates exceptional specificity and achieves a low detection limit of 3.56x 10- 2 U/mL for FEN1. The versatility of the system is further demonstrated through its ability to screen FEN1 inhibitor drugs and to distinguish FEN1 levels in real cell samples with high accuracy. The article underscores the potential of the Dz-PGM system as a promising tool for early cancer diagnosis, and in constructing sensitive detection platforms for DNA repair enzymes.
Keyword ：
DNA repair enzymes DNA repair enzymes DNAzyme DNAzyme FEN1 FEN1 Personal glucose meter Personal glucose meter Signal amplification Signal amplification
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| GB/T 7714 | Li, Mingxi , Zang, Weijie , Wang, Shuiliang et al. DNAzyme assisted single amplification for FEN1 activity detection using a personal glucose meter [J]. | ANALYTICA CHIMICA ACTA , 2025 , 1336 . |
| MLA | Li, Mingxi et al. "DNAzyme assisted single amplification for FEN1 activity detection using a personal glucose meter" . | ANALYTICA CHIMICA ACTA 1336 (2025) . |
| APA | Li, Mingxi , Zang, Weijie , Wang, Shuiliang , Lin, Zhannuo , Liu, Shu , Chen, Yiling et al. DNAzyme assisted single amplification for FEN1 activity detection using a personal glucose meter . | ANALYTICA CHIMICA ACTA , 2025 , 1336 . |
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Pyroptosis is gaining attention for its ability to activate the immune system. However, controlling the induction of specific pyroptotic tumor cell death to effectively activate the immune response is a challenge. In this study, a novel "bacterial bomb" platform is developed and designed to precisely regulate tumor cell pyroptosis using light as a trigger, thereby optimizing immune responses. The platform employs Escherichia coli (Ec) as a carrier to introduce gasdermin D (GSDMD) plasmid (pGSDMD) into Ec and adsorb photosensitizer indocyanine green (ICG) on its surface, termed as Ec-pGSDMD-ICG. ICG has photothermal effects (PTE) and photodynamic effects (PDE). Under 808 nm laser irradiation, ICG generates thermal effects and singlet oxygen (O-1(2)), leading to Ec rupture and the release of pGSDMD, which expresses sufficient GSDMD in tumor cells. Furthermore, O-1(2) and lipopolysaccharides (LPS) of Ec activate caspase pathways (caspase-1 and caspase-11), which cleave GSDMD to produce GSDMD-N, thereby inducing pyroptosis and immune responses. Light triggered Ec-pGSDMD-ICG not only efficiently induces pyroptosis in tumor cells with low GSDMD content, but also enhances the pyroptosis in tumor cells with moderate GSDMD content, all while activating the immune system for effective tumor treatment. This approach opens new strategies and research directions for pyroptosis mediated tumor immunotherapy.
Keyword ：
bacterial bomb bacterial bomb caspase pathways caspase pathways GSDMD GSDMD immunotherapy immunotherapy pyroptosis pyroptosis
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| GB/T 7714 | Liu, Yana , Zeng, Tao , Bai, Shiyan et al. Light Triggered "Bacterial Bomb" to Amplify Tumor Pyroptosis [J]. | ADVANCED FUNCTIONAL MATERIALS , 2025 . |
| MLA | Liu, Yana et al. "Light Triggered "Bacterial Bomb" to Amplify Tumor Pyroptosis" . | ADVANCED FUNCTIONAL MATERIALS (2025) . |
| APA | Liu, Yana , Zeng, Tao , Bai, Shiyan , Fang, Xiao , Cao, Xiuping , Li, Shiqing et al. Light Triggered "Bacterial Bomb" to Amplify Tumor Pyroptosis . | ADVANCED FUNCTIONAL MATERIALS , 2025 . |
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Oxygen-less dependent Type I photosensitizers (PSs) have emerged as a crucial strategy for enhancing photodynamic therapy efficiency in treating hypoxic tumors. However, solid tumors have normoxia regions situated near functional blood vessels and hypoxia regions in their interiors. To maximize the utilization of oxygen within solid tumors, herein a viable donor optimizing approach is developed to enhance both Type I&II reactive oxygen species generation of PSs. At the same mole concentration, one optimized PS (named DE) generated 9 times more O-1(2) than commercial Type II PS Chlorin e6 upon white light irradiation for 60 s. Compared to the commercial Type I PS Rose Bengal, center dot OH generation by DE is 2.9 times more under the hypoxia condition. With its optimized Type I&II pathway under normoxia and hypoxia conditions, DE is proven to be an efficient PS for solid tumor treatment, offering a promising approach for PS development.
Keyword ：
aggregation-induced emission aggregation-induced emission hypoxia hypoxia photodynamic therapy photodynamic therapy photosensitizers photosensitizers solid tumor solid tumor
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| GB/T 7714 | Liu, Xingang , Liu, Chuang , Wu, Min et al. Donor Optimizing to Boost Type I and Type II Photosensitization for Solid Tumor Therapy [J]. | ADVANCED HEALTHCARE MATERIALS , 2025 . |
| MLA | Liu, Xingang et al. "Donor Optimizing to Boost Type I and Type II Photosensitization for Solid Tumor Therapy" . | ADVANCED HEALTHCARE MATERIALS (2025) . |
| APA | Liu, Xingang , Liu, Chuang , Wu, Min , Cao, Lei , Lu, Chunhua , Liu, Bin . Donor Optimizing to Boost Type I and Type II Photosensitization for Solid Tumor Therapy . | ADVANCED HEALTHCARE MATERIALS , 2025 . |
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Lead pollution presents a significant threat to ecological systems and human health, underscoring the urgent need for highly sensitive detection methods. Herein, we introduce a novel DNA concatemer-encoded CRISPR/Cas12a fluorescence sensor (MDD-Cas12a) for sensitive detection of Pb2+ based on DNAzymes. To accomplish this, we designed a substrate strand containing a long DNA concatemer encoding multiple protospacer adjacent motifs (PAMs) and protospacer sequences for activation of the CRISPR/Cas12a system. The DNA concatemer was subsequently anchored to the surface of magnetic beads (MBs) to fabricate a MBs-DNA concatemer nanoprobe. In the presence of Pb2+, the DNAzyme structure catalyzes the cleavage of the substrate strand, leading to the release of DNA concatemers. Following magnetic separation, the released DNA concatemers significantly activate the non-specific trans-cleavage activity of the Cas12a/crRNA complex. The fluorescence reporter DNA is then completely cleaved by the activated Cas12a/crRNA complex, and the Pb2+ concentration in the sample can be quantified by measuring the fluorescence signal. By harnessing the specific recognition capability of DNAzymes for Pb2+, the programmability of DNA concatemers, and the self-amplification features of the CRISPR/Cas12a system, the MDD-Cas12a platform demonstrates high sensitivity and specificity for detecting Pb2+ in milk and lake water samples.
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| GB/T 7714 | He, Shaoying , Lin, Wei , Liu, Xin et al. A DNA concatemer-encoded CRISPR/Cas12a fluorescence sensor for sensitive detection of Pb2+ based on DNAzymes [J]. | ANALYST , 2025 . |
| MLA | He, Shaoying et al. "A DNA concatemer-encoded CRISPR/Cas12a fluorescence sensor for sensitive detection of Pb2+ based on DNAzymes" . | ANALYST (2025) . |
| APA | He, Shaoying , Lin, Wei , Liu, Xin , Li, Fei , Liang, Hong , Xu, Huo et al. A DNA concatemer-encoded CRISPR/Cas12a fluorescence sensor for sensitive detection of Pb2+ based on DNAzymes . | ANALYST , 2025 . |
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