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  1. Article ; Online: An Activatable Dual Polymer Nanosystem for Photoimmunotherapy and Metabolic Modulation of Deep-Seated Tumors.

    Liu, Gengqi / Li, Jiexin / Wang, Xiaojie / Ren, He / Zhang, Yumiao

    Advanced healthcare materials

    2024  Volume 13, Issue 9, Page(s) e2303305

    Abstract: Nanomedicine in combination with immunotherapy has shown great potential in the cancer treatment, but phototherapeutic nanomaterials that specifically activate the immunopharmacological effects in deep tumors have rarely been developed due to limited ... ...

    Abstract Nanomedicine in combination with immunotherapy has shown great potential in the cancer treatment, but phototherapeutic nanomaterials that specifically activate the immunopharmacological effects in deep tumors have rarely been developed due to limited laser penetration depth and tumor immune microenvironment. Herein, this work reports a newly synthesized semiconducting polymer (SP) grafted with imiquimod R837 and indoxmid encapsulated micelle (SPRIN-micelle) with strong absorption in the second near infrared window (NIR-II) that can relieve tumor immunosuppression and enhance the photothermal immunotherapy and catabolic modulation on tumors. Immune agonists (Imiquimod R837) and immunometabolic modulators (indoxmid) are covalently attached to NIR-II SP sensors via a glutathione (GSH) responsive self-immolation linker and then loaded into Pluronic F127 (F127) micelles by a temperature-sensitive critical micelle concentration (CMC)-switching method. Using this method, photothermal effect of SPRIN-micelles in deep-seated tumors can be activated, leading to effective tumor ablation and immunogenic cell death (ICD). Meanwhile, imiquimod and indoxmid are tracelessly released in response to the tumor microenvironment, resulting in dendritic cell (DC) maturation by imiquimod R837 and inhibition of both indoleamine 2,3-dioxygenase (IDO) activity and Treg cell expression by indoxmid. Ultimately, cytotoxic T-lymphocyte infiltration and tumor metastasis inhibition in deep solid tumors (9 mm) are achieved. In summary, this work demonstrates a new strategy for the combination of photothermal immunotherapy and metabolic modulation by developing a dual functional polymer system including activable SP and temperature-sensitive F127 for the treatment of deep solid tumors.
    MeSH term(s) Humans ; Imiquimod/pharmacology ; Polymers/pharmacology ; Micelles ; Phototherapy/methods ; Neoplasms/drug therapy ; Immunotherapy/methods ; Cell Line, Tumor ; Tumor Microenvironment ; Nanoparticles ; Polyethylenes ; Polypropylenes
    Chemical Substances Imiquimod (P1QW714R7M) ; Polymers ; Micelles ; UCON 50-HB-5100 (9038-95-3) ; Polyethylenes ; Polypropylenes
    Language English
    Publishing date 2024-02-11
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.202303305
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6966: Show issues Location:
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  2. Article ; Online: Oxygen Self-Supplied Perfluorocarbon-Modified Micelles for Enhanced Cancer Photodynamic Therapy and Ferroptosis.

    Ren, He / Hao, Minchao / Liu, Gengqi / Li, Jiexin / Jiang, Zhen / Meng, Wenlu / Zhang, Yumiao

    ACS applied bio materials

    2024  

    Abstract: Photodynamic therapy (PDT) and ferroptosis show significant potential in tumor treatment. However, their therapeutic efficacy is often hindered by the oxygen-deficient tumor microenvironment and the challenges associated with efficient intracellular drug ...

    Abstract Photodynamic therapy (PDT) and ferroptosis show significant potential in tumor treatment. However, their therapeutic efficacy is often hindered by the oxygen-deficient tumor microenvironment and the challenges associated with efficient intracellular drug delivery into tumor cells. Toward this end, this work synthesized perfluorocarbon (PFC)-modified Pluronic F127 (PFC-F127), and then exploits it as a carrier for codelivery of photosensitizer Chlorin e6 (Ce6) and the ferroptosis promoter sorafenib (Sor), yielding an oxygen self-supplying nanoplatform denoted as Ce6-Sor@PFC-F127. The PFCs on the surface of the micelle play a crucial role in efficiently solubilizing and delivering oxygen as well as increasing the hydrophobicity of the micelle surface, giving rise to enhanced endocytosis by cancer cells. The incorporation of an oxygen-carrying moiety into the micelles enhances the therapeutic impact of PDT and ferroptosis, leading to amplified endocytosis and cytotoxicity of tumor cells. Hypotonic saline technology was developed to enhance the cargo encapsulation efficiency. Notably, in a murine tumor model, Ce6-Sor@PFC-F127 effectively inhibited tumor growth through the combined use of oxygen-enhanced PDT and ferroptosis. Taken together, this work underscores the promising potential of Ce6-Sor@PFC-F127 as a multifunctional therapeutic nanoplatform for the codelivery of multiple cargos such as oxygen, photosensitizers, and ferroptosis inducers.
    Language English
    Publishing date 2024-04-18
    Publishing country United States
    Document type Journal Article
    ISSN 2576-6422
    ISSN (online) 2576-6422
    DOI 10.1021/acsabm.4c00251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: N

    Li, Jiexin / Zhang, Haisheng / Wang, Hongsheng

    Computational and structural biotechnology journal

    2022  Volume 20, Page(s) 6578–6585

    Abstract: Post-transcriptional modifications in RNAs regulate their biological behaviors and functions. ... ...

    Abstract Post-transcriptional modifications in RNAs regulate their biological behaviors and functions. N
    Language English
    Publishing date 2022-11-25
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2694435-2
    ISSN 2001-0370
    ISSN 2001-0370
    DOI 10.1016/j.csbj.2022.11.045
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: MoS

    Ling, Yongfa / Li, Jiexin / Luo, Tao / Lin, Ying / Zhang, Guangxin / Shou, Meihua / Liao, Qing

    Nanomaterials (Basel, Switzerland)

    2023  Volume 13, Issue 24

    Abstract: Memristors are recognized as crucial devices for future nonvolatile memory and artificial intelligence. Due to their typical neuron-synapse-like metal-insulator-metal(MIM) sandwich structure, they are widely used to simulate biological synapses and have ... ...

    Abstract Memristors are recognized as crucial devices for future nonvolatile memory and artificial intelligence. Due to their typical neuron-synapse-like metal-insulator-metal(MIM) sandwich structure, they are widely used to simulate biological synapses and have great potential in advancing biological synapse simulation. However, the high switch voltage and inferior stability of the memristor restrict the broader application to the emulation of the biological synapse. In this study, we report a vertically structured memristor based on few-layer MoS2. The device shows a lower switching voltage below 0.6 V, with a high ON/OFF current ratio of 104, good stability of more than 180 cycles, and a long retention time exceeding 3 × 103 s. In addition, the device has successfully simulated various biological synaptic functions, including potential/depression propagation, paired-pulse facilitation (PPF), and long-term potentiation/long-term depression (LTP/LTD) modulation. These results have significant implications for the design of a two-dimensional transition-metal dichalcogenides composite material memristor that aim to mimic biological synapses, representing promising avenues for the development of advanced neuromorphic computing systems.
    Language English
    Publishing date 2023-12-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662255-5
    ISSN 2079-4991
    ISSN 2079-4991
    DOI 10.3390/nano13243117
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  5. Article ; Online: RNA m

    Wang, Zhaotong / Zhou, Jiawang / Zhang, Haisheng / Ge, Lichen / Li, Jiexin / Wang, Hongsheng

    Molecular oncology

    2022  Volume 17, Issue 2, Page(s) 195–229

    Abstract: ... ...

    Abstract N
    MeSH term(s) Humans ; RNA/metabolism ; Methylation ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA Processing, Post-Transcriptional/genetics ; RNA, Untranslated/metabolism ; Neoplasms/genetics ; Neoplasms/metabolism
    Chemical Substances RNA (63231-63-0) ; RNA, Messenger ; RNA, Untranslated
    Language English
    Publishing date 2022-11-06
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.13326
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6637: Show issues Location:
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  6. Article ; Online: Effective Genome Editing Using CRISPR-Cas9 Nanoflowers.

    Zhang, Chen / Ren, He / Liu, Gengqi / Li, Jiexin / Wang, Xiaojie / Zhang, Yumiao

    Advanced healthcare materials

    2022  Volume 11, Issue 10, Page(s) e2102365

    Abstract: CRISPR-Cas9 as a powerful gene-editing tool has tremendous potential for the treatment of genetic diseases. Herein, a new mesoporous nanoflower (NF)-like delivery nanoplatform termed Cas9-NF is reported by crosslinking Cas9 and polymeric micelles that ... ...

    Abstract CRISPR-Cas9 as a powerful gene-editing tool has tremendous potential for the treatment of genetic diseases. Herein, a new mesoporous nanoflower (NF)-like delivery nanoplatform termed Cas9-NF is reported by crosslinking Cas9 and polymeric micelles that enables efficient intracellular delivery and controlled release of Cas9 in response to reductive microenvironment in tumor cells. The flower morphology is flexibly tunable by the protein concentration and different types of crosslinkers. Cas9 protein, embedded between polymeric micelles and protected by Cas9-NF, remains stable even under extreme pH conditions. Responsive cleavage of crosslinkers in tumor cells, leads to the traceless release of Cas9 for efficient gene knockout in nucleus. This crosslinked nanoparticle exhibits excellent capability of downregulating oncogene expression and inhibiting tumor growth in a murine tumor model. Taken together, these findings pave a new pathway toward the application of the protein-micelle crosslinked nanoflower for protein delivery, which warrants further investigations for gene regulation and cancer treatment.
    MeSH term(s) Animals ; CRISPR-Associated Protein 9/genetics ; CRISPR-Cas Systems/genetics ; Gene Editing ; Mice ; Micelles ; Nanoparticles ; Polymers/metabolism
    Chemical Substances Micelles ; Polymers ; CRISPR-Associated Protein 9 (EC 3.1.-)
    Language English
    Publishing date 2022-01-15
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.202102365
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    Zs.A 6966: Show issues Location:
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  7. Article ; Online: Metal coordination micelles for anti-cancer treatment by gene-editing and phototherapy.

    Zhang, Chen / Wang, Xiaojie / Liu, Gengqi / Ren, He / Li, Jiexin / Jiang, Zhen / Liu, Jingang / Lovell, Jonathan F / Zhang, Yumiao

    Journal of controlled release : official journal of the Controlled Release Society

    2023  Volume 357, Page(s) 210–221

    Abstract: CRISPR-Cas9 is a central focus of the emerging field of gene editing and photodynamic therapy (PDT) is a clinical-stage ablation modality combining photosensitizers with light irradiation. But metal coordination biomaterials for the applications of both ... ...

    Abstract CRISPR-Cas9 is a central focus of the emerging field of gene editing and photodynamic therapy (PDT) is a clinical-stage ablation modality combining photosensitizers with light irradiation. But metal coordination biomaterials for the applications of both have rarely been investigated. Herein, Chlorin-e6 (Ce6) Manganese (Mn) coordination micelles loaded with Cas9, termed Ce6-Mn-Cas9, were developed for augmented combination anti-cancer treatment. Manganese played multiple roles to facilitate Cas9 and single guide RNA (sgRNA) ribonucleoprotein (RNP) delivery, Fenton-like effect, and enhanced endonuclease activity of RNP. Histidine (His)-tagged RNP could be coordinated to Ce6 encapsulated in Pluronic F127 (F127) micelles by simple admixture. Triggered by ATP and endolysosomal acidic pH, Ce6-Mn-Cas9 released Cas9 without altering protein structure or function. Dual guide RNAs were designed to target the antioxidant regulator MTH1 and the DNA repair protein APE1, resulting in increased oxygen and enhanced PDT effect. In a murine tumor model, Ce6-Mn-Cas9 inhibited tumor growth with the combination therapy of PDT and gene editing. Taken together, Ce6-Mn-Cas9 represents a new biomaterial with a high degree of versatility to enable photo- and gene-therapy approaches.
    MeSH term(s) Humans ; Animals ; Mice ; Photochemotherapy/methods ; Micelles ; Manganese ; Gene Editing ; Phototherapy ; Photosensitizing Agents/chemistry ; Neoplasms/therapy ; Neoplasms/drug therapy ; Porphyrins/chemistry ; Cell Line, Tumor
    Chemical Substances Micelles ; Manganese (42Z2K6ZL8P) ; Photosensitizing Agents ; Porphyrins
    Language English
    Publishing date 2023-04-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2023.03.042
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    Zs.A 2055: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  8. Article ; Online: Rolling circle extension-assisted loop-mediated isothermal amplification (Rol-LAMP) method for locus-specific and visible detection of RNA N6-methyladenosine.

    Li, Jiexin / Zhou, Jiawang / Xia, Yan / Rui, Yalan / Yang, Xianyuan / Xie, Guoyou / Jiang, Guanmin / Wang, Hongsheng

    Nucleic acids research

    2023  Volume 51, Issue 9, Page(s) e51

    Abstract: N6-methyladenosine (m6A) is the most prevalent RNA modification in eukaryotic mRNAs. Currently available detection methods for locus-specific m6A marks rely on RT-qPCR, radioactive methods, or high-throughput sequencing. Here, we develop a non-qPCR, ... ...

    Abstract N6-methyladenosine (m6A) is the most prevalent RNA modification in eukaryotic mRNAs. Currently available detection methods for locus-specific m6A marks rely on RT-qPCR, radioactive methods, or high-throughput sequencing. Here, we develop a non-qPCR, ultrasensitive, isothermal, and naked-eye visible method for m6A detection based on rolling circle amplification (RCA) and loop-mediated isothermal amplification (LAMP), named m6A-Rol-LAMP, to verify putative m6A sites in transcripts obtained from the high-throughput data. When padlock probes hybridize to the potential m6A sites on targets, they are converted to circular form by DNA ligase in the absence of m6A modification, while m6A modification hinders the sealing of padlock probes. Subsequently, Bst DNA polymerase-mediated RCA and LAMP allow the amplification of the circular padlock probe to achieve the locus-specific detection of m6A. Following optimization and validation, m6A-Rol-LAMP can ultra-sensitively and quantitatively determine the existence of m6A modification on a specific target site as low as 100 amol under isothermal conditions. Detections of m6A can be performed on rRNA, mRNA, lincRNA, lncRNA and pre-miRNA from biological samples with naked-eye observations after dye incubation. Together, we provide a powerful tool for locus-specific detection of m6A, which can simply, quickly, sensitively, specifically, and visually determine putative m6A modification on RNA.
    MeSH term(s) Adenosine/analogs & derivatives ; Adenosine/analysis ; Adenosine/chemistry ; DNA-Directed DNA Polymerase/metabolism ; MicroRNAs/chemistry ; Nucleic Acid Amplification Techniques/methods ; Reproducibility of Results ; RNA, Long Noncoding/chemistry ; RNA, Messenger/chemistry ; RNA, Ribosomal/chemistry ; DNA Ligases/metabolism
    Chemical Substances Adenosine (K72T3FS567) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; MicroRNAs ; N-methyladenosine (CLE6G00625) ; RNA, Long Noncoding ; RNA, Messenger ; RNA, Ribosomal ; DNA Ligases (EC 6.5.1.-)
    Language English
    Publishing date 2023-03-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkad200
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    Zs.A 1067: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: Orally-Delivered, Cytokine-Engineered Extracellular Vesicles for Targeted Treatment of Inflammatory Bowel Disease.

    Liu, Jingang / Ren, He / Zhang, Chen / Li, Jiexin / Qiu, Qian / Zhang, Nan / Jiang, Ning / Lovell, Jonathan F / Zhang, Yumiao

    Small (Weinheim an der Bergstrasse, Germany)

    2023  Volume 19, Issue 50, Page(s) e2304023

    Abstract: The use of orally-administered therapeutic proteins for treatment of inflammatory bowel disease (IBD) has been limited due to the harsh gastrointestinal environment and low bioavailability that affects delivery to diseased sites. Here, a nested delivery ... ...

    Abstract The use of orally-administered therapeutic proteins for treatment of inflammatory bowel disease (IBD) has been limited due to the harsh gastrointestinal environment and low bioavailability that affects delivery to diseased sites. Here, a nested delivery system, termed Gal-IL10-EVs (C/A) that protects interleukin 10 (IL-10) from degradation in the stomach and enables targeted delivery of IL-10 to inflammatory macrophages infiltrating the colonic lamina propria, is reported. Extracellular vesicles (EVs) carrying IL-10 are designed to be secreted from genetically engineered mammalian cells by a plasmid system, and EVs are subsequently modified with galactose, endowing the targeted IL-10 delivery to inflammatory macrophages. Chitosan/alginate (C/A) hydrogel coating on Gal-IL10-EVs enables protection from harsh conditions in the gastrointestinal tract and favorable delivery to the colonic lumen, where the C/A hydrogel coating is removed at the diseased sites. Gal-IL10-EVs control the production of reactive oxygen species (ROS) and inhibit the expression of proinflammatory cytokines. In a murine model of colitis, Gal-IL10-EVs (C/A) alleviate IBD symptoms including inflammatory responses and disrupt colonic barriers. Taken together, Gal-IL10-EVs (C/A) features biocompatibility, pH-responsive drug release, and macrophage-targeting as a therapeutic platform for oral delivery of bioactive proteins for treating intestinal diseases.
    MeSH term(s) Mice ; Animals ; Cytokines ; Interleukin-10 ; Inflammatory Bowel Diseases/drug therapy ; Inflammatory Bowel Diseases/metabolism ; Extracellular Vesicles/metabolism ; Chitosan ; Hydrogels ; Mammals
    Chemical Substances Cytokines ; Interleukin-10 (130068-27-8) ; Chitosan (9012-76-4) ; Hydrogels
    Language English
    Publishing date 2023-09-20
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2168935-0
    ISSN 1613-6829 ; 1613-6810
    ISSN (online) 1613-6829
    ISSN 1613-6810
    DOI 10.1002/smll.202304023
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  10. Article ; Online: Small molecule-inducible and photoactivatable cellular RNA N1-methyladenosine editing.

    Xie, Guoyou / Lu, Yunqing / He, Jiaxin / Yang, Xianyuan / Zhou, Jiawang / Yi, Cheng / Li, Jian / Li, Zigang / Asadikaram, Gholamreza / Niu, Hongxin / Xiong, Xiaofeng / Li, Jiexin / Wang, Hong-Sheng

    Angewandte Chemie (International ed. in English)

    2024  , Page(s) e202320029

    Abstract: N1-methyladenosine (m1A) modification is one of the most prevalent epigenetic modifications on RNA. Given the vital role of m1A modification in RNA processing such as splicing, stability and translation, developing a precise and controllable m1A editing ... ...

    Abstract N1-methyladenosine (m1A) modification is one of the most prevalent epigenetic modifications on RNA. Given the vital role of m1A modification in RNA processing such as splicing, stability and translation, developing a precise and controllable m1A editing tool is pivotal for in-depth investigating the biological functions of m1A. In this study, we developed an abscisic acid (ABA)-inducible and reversible m1A demethylation tool (termed AI-dm1A), which targets specific transcripts by combining the chemical proximity-induction techniques with the CRISPR/dCas13b system and ALKBH3. We successfully employed AI-dm1A to selectively demethylate the m1A modifications at MALAT1 A8422, and this demethylation process could be reversed by removing ABA. Furthermore, we validated its demethylating function on various types of cellular RNAs including mRNA, rRNA and lncRNA. Additionally, we used AI-dm1A to specifically demethylate m1A on ATP5D mRNA, which promoted ATP5D expression and enhanced the glycolysis activity of tumor cells. Conversely, by replacing the demethylase ALKBH3 with methyltransferase TRMT61A, we also developed a controllable m1A methylation tool, namely AI-m1A. Finally, we caged ABA by 4,5-dimethoxy-2-nitrobenzyl (DMNB) to achieve light-inducible m1A methylation or demethylation on specific transcripts. Collectively, our m1A editing tool enables us to flexibly study how m1A modifications on specific transcript influence biological functions and phenotypes.
    Language English
    Publishing date 2024-04-09
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.202320029
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