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学者姓名：卢春华
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Abstract ：
The combination of chemotherapy and gene therapy holds great promise for the treatment and eradication of tumors. However, due to significant differences in physicochemical properties between chemotherapeutic agents and functional nucleic acid drugs, direct integration into a single nano -agent is hindered, impeding the design and construction of an effective co-delivery nano-platform for synergistic anti -tumor treatments. In this study, we have developed an mRNA-responsive two-in-one nano-drug for effective anti -tumor therapy by the direct selfassembly of 2 ' -fluoro-substituted antisense DNA against P-glycoprotein (2 ' F-DNA) and chemo drug paclitaxel (PTX). The 2 ' -fluoro modification of DNA could significantly increase the interaction between the therapeutic nucleic acid and the chemotherapeutic drug, promoting the successful formation of 2 ' F-DNA/PTX nanospheres (2 ' F-DNA/PTX NSs). Due to the one-step self-assembly process without additional carrier materials, the prepared 2 ' F-DNA/PTX NSs exhibited considerable loading efficiency and bioavailability of PTX. In the presence of endogenous P-glycoprotein mRNA, the 2 ' F-DNA/PTX NSs were disassembled. The released 2 ' F-DNA could downregulate the expression of P-glycoprotein, which decreased the multidrug resistance of tumor cells and enhanced the chemotherapy effect caused by PTX. In this way, the 2 ' F-DNA/PTX NSs could synergistically induce the apoptosis of tumor cells and realize the combined anti -tumor therapy. This strategy might provide a new tool to explore functional intracellular co-delivery nano -systems with high bioavailability and exhibit potential promising in the applications of accurate diagnosis and treatment of tumors.
Keyword ：
Carrier-free Carrier-free Chemotherapy Chemotherapy Gene silence Gene silence Nano-drug Nano-drug Synergistic treatment Synergistic treatment
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| GB/T 7714 | Liu, Yongfei , Lin, Yuhong , Xiao, Han et al. mRNA-responsive two-in-one nanodrug for enhanced anti-tumor chemo-gene therapy [J]. | JOURNAL OF CONTROLLED RELEASE , 2024 , 369 : 765-774 . |
| MLA | Liu, Yongfei et al. "mRNA-responsive two-in-one nanodrug for enhanced anti-tumor chemo-gene therapy" . | JOURNAL OF CONTROLLED RELEASE 369 (2024) : 765-774 . |
| APA | Liu, Yongfei , Lin, Yuhong , Xiao, Han , Fu, Zhangcheng , Zhu, Xiaohui , Chen, Xiaoyong et al. mRNA-responsive two-in-one nanodrug for enhanced anti-tumor chemo-gene therapy . | JOURNAL OF CONTROLLED RELEASE , 2024 , 369 , 765-774 . |
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DNA材料具有的特异性、可编程性和生物相容性，使得其在生物检测和药物递送方面具有很大的应用优势。为了进一步拓展DNA材料的应用和合成方法，本文报道了利用DNA与金属离子之间的配合作用，简单高效地制备具有肿瘤标志物micro RNA-21(mi R-21)响应性的Zn~(2+)/DNA自组装纳米粒子（ZDNPs）。通过粒子中DNA发卡结构与mi R-21的特异性互补，激活荧光信号并释放Zn~(2+)，导致细胞内产生大量活性氧，从而用于肿瘤的荧光成像和氧化应激治疗。合成的ZDNPs为形状均匀的球形粒子，能有效对Zn~(2+)进行装载。通过ZDNPs对mi R-21的响应性实验，验证了ZDNPs与miR-21浓度之间具有良好的线性响应荧光信号，线性响应范围在5～160 nmol/L，检测限为5 nmol/L，且具备特异性。此外，本文对ZDNPs在细胞内的作用效果也进行了研究，结果表明其能在肿瘤细胞内进行响应性的荧光成像，并能通过氧化应激途径介导肿瘤细胞凋亡。在活体的荧光成像和肿瘤治疗中，ZDNPs在肿瘤病灶部位体现出特异性和持续性的示踪能力，并且对肿瘤产生了明显的生长抑制效果。
Keyword ：
DNA发卡 DNA发卡 microRNA-21 microRNA-21 氧化应激治疗 氧化应激治疗 肿瘤成像 肿瘤成像 锌离子 锌离子
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| GB/T 7714 | 徐昕 , 李烨 , 王敏 et al. 基于microRNA-21响应的Zn~(2+)/DNA自组装体用于肿瘤的检测和氧化应激治疗 [J]. | 应用化学 , 2024 , 41 (01) : 164-174 . |
| MLA | 徐昕 et al. "基于microRNA-21响应的Zn~(2+)/DNA自组装体用于肿瘤的检测和氧化应激治疗" . | 应用化学 41 . 01 (2024) : 164-174 . |
| APA | 徐昕 , 李烨 , 王敏 , 傅章程 , 齐国敏 , 卢春华 . 基于microRNA-21响应的Zn~(2+)/DNA自组装体用于肿瘤的检测和氧化应激治疗 . | 应用化学 , 2024 , 41 (01) , 164-174 . |
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Ferroptosis, a newly discovered form of regulated cell death, has garnered significant attention in the field of tumor therapy. However, the presence of overexpressed glutathione (GSH) and insufficient levels of H2O2 in the tumor microenvironment (TME) hinders the occurrence of ferroptosis. In response to these challenges, here we have constructed the self-assembled nanocomplexes (FeE NPs) utilizing epigallocatechin-3-gallate (EGCG) from green tea polyphenols and metal ions (Fe3+) as components. After grafting PEG, the nanocomplexes (FeE@PEG NPs) exhibit good biocompatibility and synergistically enhanced tumor-inhibitory properties. FeE@PEG NPs can be disassembled by H2O2 in the TME, leading to the rapid release of Fe3+ and EGCG. The released Fe3+ produces large amounts of toxic center dot OH by the Fenton reactions while having minimal impact on normal cells. The generated center dot OH effectively induces lipid peroxidation, which leads to ferroptosis in tumor cells. Meanwhile, the released EGCG can autoxidize to produce H2O2, which further promotes the production of center dot OH radicals and increases lipid peroxide levels. Moreover, EGCG also depletes the high levels of intracellular GSH, leading to an intracellular redox imbalance and triggering ferroptosis. This study provides new insights into advancing anticancer ferroptosis through rational material design, offering promising avenues for future research.
Keyword ：
Epigallocatechin-3-gallate Epigallocatechin-3-gallate Ferroptosis Ferroptosis GSH depletion GSH depletion Self-assembly Self-assembly
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| GB/T 7714 | Wang, Min , Yu, Aoling , Han, Wen et al. Self-assembled metal-phenolic nanocomplexes comprised of green tea catechin for tumor-specific ferroptosis [J]. | MATERIALS TODAY BIO , 2024 , 26 . |
| MLA | Wang, Min et al. "Self-assembled metal-phenolic nanocomplexes comprised of green tea catechin for tumor-specific ferroptosis" . | MATERIALS TODAY BIO 26 (2024) . |
| APA | Wang, Min , Yu, Aoling , Han, Wen , Chen, Jingyi , Lu, Chunhua , Tu, Xiankun . Self-assembled metal-phenolic nanocomplexes comprised of green tea catechin for tumor-specific ferroptosis . | MATERIALS TODAY BIO , 2024 , 26 . |
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As digital data undergo explosive growth, deoxyribonucleic acid (DNA) has emerged as a promising storage medium due to its high density, longevity, and ease of replication, offering vast potential in data storage solutions. This study focuses on the protection and retrieval of data during the DNA storage process, developing a technique that employs flow cytometry sorting (FCS) to segregate multicolored fluorescent DNA microparticles encoded with data and facilitating efficient random access. Moreover, the encapsulated fluorescent DNA microparticles, formed through layer-by-layer self-assembly, preserve structural and sequence integrity even under harsh conditions while also supporting a high-density DNA payload. Experimental results have shown that the encoded data can still be successfully recovered from encapsulated DNA microparticles following de-encapsulation. We also successfully demonstrated the automated encapsulation process of fluorescent DNA microparticles using a microfluidic chip. This research provides an innovative approach to the long-term stability and random readability of DNA data storage. © 2024 American Chemical Society.
Keyword ：
Data encapsulation Data encapsulation Encapsulation Encapsulation Random access storage Random access storage
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| GB/T 7714 | Zhong, Wukun , Geng, Chunyang , Fu, Zhangcheng et al. Flow Cytometry Sorting for Random Access in DNA Data Storage: Encapsulation for Enhanced Stability and Sequence Integrity of DNA [J]. | Analytical Chemistry , 2024 , 96 (40) : 16099-16108 . |
| MLA | Zhong, Wukun et al. "Flow Cytometry Sorting for Random Access in DNA Data Storage: Encapsulation for Enhanced Stability and Sequence Integrity of DNA" . | Analytical Chemistry 96 . 40 (2024) : 16099-16108 . |
| APA | Zhong, Wukun , Geng, Chunyang , Fu, Zhangcheng , Mao, Cuiping , Zheng, Yanlin , Wang, Saijie et al. Flow Cytometry Sorting for Random Access in DNA Data Storage: Encapsulation for Enhanced Stability and Sequence Integrity of DNA . | Analytical Chemistry , 2024 , 96 (40) , 16099-16108 . |
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DNA-based molecular amplifiers offer significant promise for molecular-level disease diagnosis and treatment, yet tailoring their activation for precise timing and localization remains a challenge. Herein, we've pioneered a dual activation strategy harnessing external light and internal ATP to create a highly controlled DNA logic amplifier (FDLA) for accurate miRNA monitoring in cancer cells. The FDLA was constructed by tethered the two functionalized catalytic hairpin assembly (CHA) hairpin modules (ATP aptamer sealed hairpin aH1 and photocleavable (PC-linker) sites modified hairpin pH2) to DNA tetrahedron (DTN). The FDLA system incorporates ATP aptamers and PC-linkers as logic control units, allowing them to respond to both exogenous UV light and endogenous ATP present within cancer cells. This response triggers the release of CHA hairpin modules, enabling amplified FRET miRNA imaging through an AND-AND gate. The DTN structure could improve the stability of FDLA and accelerate the kinetics of the strand displacement reaction. It is noteworthy that the UV and ATP cogated DNA circuit can control the DNA bio-computing at specific time and location, offering spatial and temporal capabilities that can be harnessed for miRNA imaging. Furthermore, the miRNA-sensing FDLA amplifier demonstrates reliable imaging of intracellular miRNA with minimal background noise and false-positive signals. This highlights the feasibility of utilizing both exogenous and endogenous regulatory strategies to achieve spatial and temporal control of DNA molecular circuits within living cancer cells. Such advancements hold immense potential for unraveling the correlation between miRNA and associated diseases.
Keyword ：
DNA amplifier DNA amplifier Framework nucleic acids Framework nucleic acids Logic gates Logic gates MicroRNA imaging MicroRNA imaging
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| GB/T 7714 | Zheng, Yanlin , Li, Liannishang , Chen, Yiling et al. Construction of an exogenously and endogenously Co-activated DNA logic amplifier for highly reliable intracellular MicroRNA imaging [J]. | BIOSENSORS & BIOELECTRONICS , 2024 , 259 . |
| MLA | Zheng, Yanlin et al. "Construction of an exogenously and endogenously Co-activated DNA logic amplifier for highly reliable intracellular MicroRNA imaging" . | BIOSENSORS & BIOELECTRONICS 259 (2024) . |
| APA | Zheng, Yanlin , Li, Liannishang , Chen, Yiling , Lin, Zhannuo , Ruan, Xiaohui , Lin, Qitian et al. Construction of an exogenously and endogenously Co-activated DNA logic amplifier for highly reliable intracellular MicroRNA imaging . | BIOSENSORS & BIOELECTRONICS , 2024 , 259 . |
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Nanodrugs composed of pure pharmacologically active molecules have been extensively researched as emerging nanomedicines for cancer treatment. However, traditional preparation approaches are generally limited by low production rates, complicated preparation processes, and high production costs. Here, we presented a simple strategy for constructing drug-based nanoparticles (2 ' F-ASO/CPT NPs) consisting of pure therapeutic molecules by utilizing 2 '-fluoro-substituted antisense oligonucleotide (2 ' F-ASO)-mediated self-assembly with the anticancer agent camptothecin (CPT). The 2 ' F-substitution could enhance the intermolecular interactions between DNA and CPT through electrostatic and dispersion interactions. The resulting 2 ' F-ASO/CPT NPs had a high drug loading capacity and improved drug stability. 2 ' F-ASO/CPT NPs could specifically respond to P-glycoprotein (P-gp) mRNA and inhibit the expression of P-gp, protecting CPT from P-gp-mediated drug efflux. Therefore, the synergistic anticancer effect caused by 2 ' F-ASO/CPT NPs could be successfully achieved. This work presented a new 2 ' F-ASO-mediated drug self-assembly strategy for carrier-free chemotherapy-gene therapy with the potential to enhance cancer treatment efficacy.
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| GB/T 7714 | Fu, Zhangcheng , Lin, Yuhong , Xiao, Han et al. 2′-Fluorinated Antisense Oligonucleotide-Mediated Drug Self-Assembly Strategy for the Efficient Synergistic Anti-Tumor Therapy [J]. | ACS MATERIALS LETTERS , 2024 , 6 (7) : 2582-2590 . |
| MLA | Fu, Zhangcheng et al. "2′-Fluorinated Antisense Oligonucleotide-Mediated Drug Self-Assembly Strategy for the Efficient Synergistic Anti-Tumor Therapy" . | ACS MATERIALS LETTERS 6 . 7 (2024) : 2582-2590 . |
| APA | Fu, Zhangcheng , Lin, Yuhong , Xiao, Han , Wang, Haihui , Liu, Yongfei , Gong, Yurong et al. 2′-Fluorinated Antisense Oligonucleotide-Mediated Drug Self-Assembly Strategy for the Efficient Synergistic Anti-Tumor Therapy . | ACS MATERIALS LETTERS , 2024 , 6 (7) , 2582-2590 . |
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Catalytic DNA circuits show great potential for precise intracellular imaging. However, their selectivity and efficiency are often hindered by low anti-interference performance in the cytoplasm 's complex environment. Thus, designing DNA circuits that exhibit enhanced stability and specific activation is crucial for the accurate intracellular biomolecule imaging. Herein, we proposed a framework nucleic acids based endogenously activated entropy-driven catalytic (EDC) circuit, FEED, for in vivo microRNA imaging with enhanced selectivity and efficiency. To mitigate undesired signal leakage before reaching the target cells, the dominating EDC circuitry fuel strand was initially blocked with a disulfide bond modified DNA strand, and the target recognition site of sensing module was also closed by apurinic/apyrimidinic (AP) sites. This configuration allowed selective activation of the EDC by endogenous GSH and human apurinic/apyrimidinic endonuclease 1 (APE1) in cancer cells, facilitating high-contrast miRNA imaging. Additionally, the integrating a distinctive DNA tetrahedral structure into the EDC circuit enhances both biostability and cellular reaction efficacy. This in-site activation FEED circuit offers a programmable and modular amplification strategy for biomarker detection in live cells and mice, providing a potentially valuable molecular tool for living systems.
Keyword ：
Catalytic DNA Circuit Catalytic DNA Circuit Entropy-Driven Entropy-Driven Framework nucleic acids Framework nucleic acids MicroRNA Imaging MicroRNA Imaging
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| GB/T 7714 | Li, Liannishang , Gong, Yurong , Lin, Qitian et al. A GSH/APE1-controlled framework nucleic acids based entropy-driven DNA circuit for high-contrast miRNAs imaging [J]. | SENSORS AND ACTUATORS B-CHEMICAL , 2024 , 417 . |
| MLA | Li, Liannishang et al. "A GSH/APE1-controlled framework nucleic acids based entropy-driven DNA circuit for high-contrast miRNAs imaging" . | SENSORS AND ACTUATORS B-CHEMICAL 417 (2024) . |
| APA | Li, Liannishang , Gong, Yurong , Lin, Qitian , He, Shaoying , Xing, Chao , Lu, Chunhua . A GSH/APE1-controlled framework nucleic acids based entropy-driven DNA circuit for high-contrast miRNAs imaging . | SENSORS AND ACTUATORS B-CHEMICAL , 2024 , 417 . |
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DNAzyme-based gene regulation shows great potential for the therapy of many cancers. However, inef-fective delivery and insufficient cofactor supply pose challenges for potent gene therapy. In this study, we constructed a smart metal-polyphenol-DNAzyme nanoplatform (TA-Mn@Dz NPs) with intrinsic stabil-ity, effective delivery, and cofactor self-supply ability for gene-chemodynamic synergistic tumor therapy. Tannic acid, a plant-derived polyphenol, acts as an intermediate structural unit to mediate the assem-bly of Mn2+/DNAzyme and tumor acid environment-responsive nanocarriers. Intracellularly, the acidic environment triggers the decomposition of TA-Mn@Dz NPs to release DNAzyme and Mn2+. The Mn2+ ion not only boosts the catalytic cleavage of surviving mRNA for effective gene therapy but also acti-vates chemodynamic therapy (CDT), generating highly toxic & BULL;OH from endogenous H2O2. When tail in-travenously injected into MCF-7 tumor-bearing mice, the TA-Mn@Dz NPs display desirable synergistic gene-chemodynamic antitumor effects, paving the way for developing DNAzyme-based multifunctional theranostic platforms for biomedical applications.Statement of significance1. A smart metal-polyphenol-DNAzyme nanoplatform was constructed for gene-chemodynamic syner-gistic tumor therapy. 2. Tannic acid act as intermediate structural units to mediate the assembly of Mn2+/DNAzyme and tumor acid environment-responsive nanocarriers. 3. The Mn2+-ion could not only boost the catalytic cleavage of surviving mRNA for effective gene therapy, but also catalyze endogenous H2O2 to form cytotoxic hydroxyl radicals for chemodynamic therapy. 4. Our work paves an extremely simple way to integrate gene therapy with CDT for the dual-catalytic tumor treatment.& COPY; 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Keyword ：
Chemodynamic therapy Chemodynamic therapy DNAzyme DNAzyme Gene therapy Gene therapy Metal cofactor Metal cofactor Polyphenol Polyphenol
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| GB/T 7714 | Xing, Chao , Lin, Qitian , Chen, Yiting et al. A smart metal-polyphenol-DNAzyme nanoplatform for gene-chemodynamic synergistic tumor therapy [J]. | ACTA BIOMATERIALIA , 2023 , 167 : 564-573 . |
| MLA | Xing, Chao et al. "A smart metal-polyphenol-DNAzyme nanoplatform for gene-chemodynamic synergistic tumor therapy" . | ACTA BIOMATERIALIA 167 (2023) : 564-573 . |
| APA | Xing, Chao , Lin, Qitian , Chen, Yiting , Zeng, Sijie , Wang, Jun , Lu, Chunhua . A smart metal-polyphenol-DNAzyme nanoplatform for gene-chemodynamic synergistic tumor therapy . | ACTA BIOMATERIALIA , 2023 , 167 , 564-573 . |
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Small molecule aptamers discovered by traditional selection methods usually lack conformational changes upon target binding. This limits the use of aptamers as molecular probes for small molecule detection and regulatory elements of genetic circuits. Here, we report a new method called capture and in vitro transcription-systematic evolution of ligands by exponential enrichment (CIVT-SELEX) to select DNA aptamers that can not only bind to small molecule ligands but also undergo significant conformational changes. Through this method, we select a structure-switching aptamer of uridine-5 '-diphosphate (UDP). Taking advantage of its conformational changes, we first construct a UDP-responsive transcriptional switch by inserting the aptamer in a genetic circuit and demonstrate that it can respond to the addition of UDP and regulate the transcription of downstream genes. We also build a UDP aptamer-based biosensor that can be used for active glycosyltransferase screening. We believe this method can provide a universal platform for selecting small molecule aptamers with conformational changes and expand the use of aptamers in small molecule detection and genetic regulation.
Keyword ：
aptamers aptamers biosensors biosensors CIVT-SELEX CIVT-SELEX conformational change conformational change small molecule small molecule
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| GB/T 7714 | Guo, Shaobin , Lin, Jingjing , Lin, Lujie et al. Selecting small molecule DNA aptamers with significant conformational changes for constructing transcriptional switches and biosensors [J]. | SCIENCE CHINA-CHEMISTRY , 2023 , 66 (5) : 1529-1536 . |
| MLA | Guo, Shaobin et al. "Selecting small molecule DNA aptamers with significant conformational changes for constructing transcriptional switches and biosensors" . | SCIENCE CHINA-CHEMISTRY 66 . 5 (2023) : 1529-1536 . |
| APA | Guo, Shaobin , Lin, Jingjing , Lin, Lujie , Xu, Wen , Guo, Yan , Xu, Zipeng et al. Selecting small molecule DNA aptamers with significant conformational changes for constructing transcriptional switches and biosensors . | SCIENCE CHINA-CHEMISTRY , 2023 , 66 (5) , 1529-1536 . |
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The physicochemical differences between DNA and other molecules pose a challenge to the construction of DNA based nanostructures. Herein, we propose a straightforward approach for preparing multifunctional DNA-based nanospheres through direct self-assembly of 2'-fluoro-substituted single-stranded DNA (2'F-DNA) with various small molecules. Molecular dynamics simulation revealed that 2'F substitution in DNA can cause the repulsion of adjacent PO(4)(3-)group, leading to local stretching of the DNA structure. Moreover, 2'F substituent induced the regular polarization of H2O nearby F to form the hydration layer, which interrupts inherent interactions among bases. In this way, the bases of 2'F-DNA chain have fewer constraints and more flexibility in conformation, facilitating their non-covalent interactions with other molecules and enhancing the self-assembly capacity of 2'F-DNA. Consequently, 2'F-DNA can bind to more molecules, tending to spontaneously form hybrid DNA nano spheres. Following this approach, a chemo-gene therapy 2'F-DNA/doxorubicin model was designed, showing the significant synergistic anti-tumor therapeutic efficacy. Taken together, this study provides an expandable approach for constructing engineering hybrid nanospheres using DNA and other small molecules, which holds great potential for further biological applications.
Keyword ：
2'F-DNA 2'F-DNA Chemo-gene therapy Chemo-gene therapy Dynamics simulation Dynamics simulation Self-assembly Self-assembly
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| GB/T 7714 | Wang, Haihui , Jiang, Yifan , Liu, Yichang et al. 20.625pt'0.625pt-Fluoro-substituted DNA-induced self-assembly strategy for engineering hybrid nanospheres [J]. | CHEMICAL ENGINEERING JOURNAL , 2023 , 471 . |
| MLA | Wang, Haihui et al. "20.625pt'0.625pt-Fluoro-substituted DNA-induced self-assembly strategy for engineering hybrid nanospheres" . | CHEMICAL ENGINEERING JOURNAL 471 (2023) . |
| APA | Wang, Haihui , Jiang, Yifan , Liu, Yichang , Zhu, Xiaohui , Liu, Yongfei , Chen, Minle et al. 20.625pt'0.625pt-Fluoro-substituted DNA-induced self-assembly strategy for engineering hybrid nanospheres . | CHEMICAL ENGINEERING JOURNAL , 2023 , 471 . |
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