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Photothermal probiotics delivery of photodynamic agents for enhanced immunogenic cell death within hypoxia center of solid tumors

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Nano Research 2025年第1期18卷 642-652页

作者： Wen Luo Shiyu Du Yateng Jiang Bangshun He Jun Tang Jingjing Yang Yujun Song Jiangsu key laboratory of Artificial Functional Materials State Key Laboratory of Analytical Chemistry for Life ScienceNational Laboratory of Solid State MicrostructuresCollege of Engineering and Applied SciencesNanjing UniversityNanjing 210023China Department of laboratory Medicine Nanjing First HospitalNanjing Medical UniversityNanjing 210006China Department of Anesthesiology Jinling HospitalMedical School of Nanjing UniversityNanjing 210000China Department of Biochemistry and Molecular biology School of Medicine&Holistic Integrative MedicineJiangsu Collaborative Innovation Center of Chinese Medicinal Resources IndustrializationNanjing University of Chinese MedicineNanjing 210023China

Resulting from harsh hypoxic environmental conditions,central cells in the core of solid tumors are usually more aggressive and malignant with a less stable ***,therapeutic agents with improved penetration for the activation of immunity in tumor centers exhibit promising potential in ***,polydopamine-coated Escherichia coli Nissle 1917(EcN)bearing chlorin e6(Ce6)-loaded and polyethyleneimine(PEI)-coated hollow manganese dioxide(shorted as EP-ChP)are applied for enhanced immunotherapy in deep *** accumulation in tumor center through hypoxia targeting,manganese dioxide is degradated under the tumor microenvironment with released Ce6 and thus generates reactive oxygen species(ROS)upon 660 nm laser irradiation,which can further lower thermalresistance of cancer cells via HSP90α*** to that,heating induced by polydopamine upon 808 nm laser irradiation can achieve effective tumor *** upon dual laser induces enhanced immunogenic cell death,while bacterial infections in tumor tissues also trigger innate *** bacteria-based approach provides enhanced antitumor immune responses in deep tumors with great potential in the reshaping of immunosuppression tumor microenvironment.

关键词： bacteria phototherapies immunotherapy hypoxia targeting tumor penetration

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Manipulating the intramolecular motion of AIEgens for boosted biomedical applications

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Science China Chemistry 2019年第8期62卷 929-932页

作者： Hanlin Ou Shuxin Dai Ruihua Liu Dan Ding key laboratory of Bioactive Materials Ministry of EducationState Key Laboratory of Medicinal Chemical BiologyCollege of Life SciencesNankai University

The research in the biomedical applications of aggregation? induced emission luminogens (AIEgens) has attracted increasing interest in recent years, as AIEgens have been widely accepted as promising materials for constructing new generation of phototheranostic agents [1-5]. Different from conventional organic dyes, the AIEgens often have threedimensional (3D) molecular structure and contain a number of intramolecular motion units [6-8]. In the aggregates, the 3D molecular structure results in significantly reduced intermolecular interaction such as π-π stacking as compared to planar structure.

关键词： Manipulating intramolecular biomedical applications

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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期 308-316页

作者： Sili Wang Jiancheng Huang Yanan Du Wei Huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying Bian Wen Liu state key laboratory of chemical biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences state key laboratory of Microbial Technology Shandong University National Health Commission (NHC) key laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

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Construction and evaluation of co-electrospun poly (butylene succinate)/gelatin materials as potential vascular grafts

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Chinese Journal of chemical Engineering 2021年第11期34卷 297-305页

作者： Tingting Yang Han Xu Congrui Zhao Di Tang Fan Mu Hongjiang Lu Zhoufeng Rao Shufang Wang state key laboratory of medicinal chemical biology Key Laboratory of Bioactive Materials for Ministry of EducationCollege of Life SciencesNankai UniversityTianjin 300071China

In this study,a series of poly(butylene succinate)(PBSU)/gelatin composites were prepared by *** morphology,physicochemical analysis,biomechanical properties,biocompatibility,and biodegradability of the materials were *** results showed that the ultimate tensile stress of the vascular PBSU/gelatin grafts at(95/5),(90/10),(85/15),and(80/20)was(4.17±0.54)MPa,(3.81±0.44)MPa,2.94±0.69 MPa and 2.11±0.72 MPa respectively,and the burst pressure was(282.7±22.3)kPa,(295.3±3.9)kPa,(306.8±13.9)kPa and(307.6±9.0)kPa respectively,which met the requirements of tissue-engineered blood ***,the addition of gelatin improved the hydrophilicity and degradation properties of PBSU,thus enhancing cell adhesion and promoting the inward growth of vascular smooth muscle *** summary,the research in this paper provides a useful reference for the preparation and optimization of vascular scaffolds.

关键词： Poly(butylene succinate) Gelatin Co-electrospinning Degradation Vascular graft

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Exosome-mimicking nanovesicles derived from efficacy-potentiated stem cell membrane and secretome for regeneration of injured tissue

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Nano Research 2022年第8期15卷 1680-1690页

作者： Chunxiao Qi Xiangsheng Liu Dengke Zhi Yifan Tai Yufei Liu Qiqi Sun Kai Wang Shufang Wang Adam C.Midgley Deling Kong key laboratory of Bioactive Materials Ministry of EducationCollege of Life Sciencesand State Key Laboratory of Medicinal Chemical BiologyNankai UniversityTianjin 300071China

Translation of exosome-based therapies to pharmaceutical use is hindered by difficulties in large-scale and cost-effective production of clinical-grade *** rational design of nanovesicles that mimic the functionalities and physicochemical properties of exosomes may circumvent these *** this study,membranes and secretome from efficacy-potentiated mesenchymal stem cells(MSCs)were developed into size-controllable nanovesicles(Meseomes).MSCs were primed with interferon-y(IFNy)and tumor necrosis factor-a(TNFa),harvested,and exosome-mimicking Meseomes were subsequently synthesized via one-step *** demonstrated significant enhancement of pro-angiogenic,pro-proliferative,antiinflammatory,and anti-fibrotic effects on endothelial cells,macrophages,and hepatic stellate cells in *** from primed MSCs benefited from an enrichment of bioactive and therapeutic molecules compared to nanovesicles from unprimed MSCs,as validated by liquid chromatography-mass spectrometry(LC-MS)proteomic *** administration of Meseomes to acute liver injury models resulted in the recovery of liver function,attenuated tissue *** assessment of locally administered Meseomes in acute hindlimb ischemia models resulted in the salvage of the majority of the ischemic hindlimb(>80%),which was due to enhanced angiogenesis and M2 macrophage *** versatility and therapeutic efficacy of our developed acellular Meseomes offer an appealing alternative to traditional cell or exosome therapies for regenerative and translational medicine.

关键词： acellular therapy biomimetic nanovesicles acute liver injury hindlimb ischemia regenerative medicine

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Ca^(2+)-calpains axis regulates Yki stability and activity in Drosophila

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Journal of Genetics and Genomics 2024年第10期51卷 1020-1029页

作者： Chaojun Zhai Yunfeng Wang Shenao Qi Muhan Yang Shian Wu The state key laboratory of medicinal chemical biology Tianjin Key Laboratory ofProtein SciencesCollege of Life SciencesNankai UniversityTianjin 300071China

Yorkie(Yki)is a key effector of the Hippo pathway that activates the expression of targets by associating with the transcription factor *** upstream signals,such as cell polarity and mechanical cues,control transcriptional programs by regulating Yki *** for Yki regulatory factors has far-reaching significance for studying the Hippo pathway in development and human *** this study,we identify Calpain-A(CalpA)and Calpain-B(CalpB),two calcium(Ca^(2+))-dependent modulatory proteases of the calpain family,as critical regulators of Yki in Drosophila that interact with Yki,***^(2+)induces Yki cleavage in a CalpA/CalpB-dependent manner,and the protease activity of CalpA/CalpB is pivotal for the ***,overexpression of CalpA or CalpB in Drosophila partially restores the large wing phenotype caused by Yki overexpression,and F98 of Yki is an important cleavage site by the Ca^(2+)-calpains *** study uncovers a unique mechanism whereby the Ca^(2+)-calpain axis modulates Yki activity throughprotein cleavage.

关键词： CalpA CalpB Calcium Hippo pathway Yki Drosophila

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Hepatitis B virus X protein accelerates the development of hepatoma

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Cancer biology & Medicine 2014年第3期11卷 182-190页

作者： Xiao-Dong Zhang Yuan Wang Li-Hong Ye Department of Cancer Research College of Life SciencesState Key Laboratory of Medicinal Chemical BiologyNankai University Department of Biochemistry College of Life SciencesState Key Laboratory of Medicinal Chemical BiologyNankai University

The chronic infection of hepatitis B virus(HBV) is closely related to the occurrence and development of hepatocellular carcinoma(HCC). Accumulated evidence has shown that HBV X protein(HBx protein) is a multifunctional regulator with a crucial role in hepatocarcinogenesis. However, information on the mechanism by which HBV induces HCC is lacking. This review focuses on the pathological functions of HBx in HBV-induced hepatocarcinogenesis. As a transactivator, HBx can modulate nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB) and transcription factor AP-2. Moreover, HBx can affect regulatory non-coding RNAs(ncRNAs) including microRNAs and long ncRNAs(lncRNAs), such as miRNA-205 and highly upregulated in liver cancer(HULC), respectively. HBx is also involved in epigenetic modification, including methylation and acetylation. HBx interacts with various signal-transduction pathways, such as protein kinase B/Akt, Wnt/β-catenin, signal transducer and activator of transcription, and NF-κB pathways. Moreover, HBx affects cellular fate by shifting the balance toward cell survival. HBx may lead to the loss of apoptotic functions or directly contributes to oncogenesis by achieving transforming functions, which induce hepatocarcinogenesis. Additionally, HBx can modulate apoptosis and immune response by direct or indirect interaction with host factors. We conclude that HBx hastens the development of hepatoma.

关键词： Hepatocellular carcinoma(HCC) hepatitis B virus(HBV) HBV X protein(HBx protein) hepatocarcinogenesis

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Revealing drug targets with multimodal bioorthogonal AMPD probes through visual metabolic labeling

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Chinese chemical Letters 2024年第12期35卷 433-438页

作者： Fukui Shen Yuqing Zhang Guoqing Luan Kaixue Zhang Zhenzhen Wang Yunhao Luo Yuanyuan Hou Gang Bai state key laboratory of medicinal chemical biology College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai University college of life sciences Nankai University

Multimodal bioorthogonal small molecule probes play a pivotal role in drug-focused biomedical ***,existing drug tracking and imaging techniques face obstacles in living organisms,hindering precise drug localization and target protein ***,we introduced a multimodal probe named 1-(azidomethyl)pyrene-4,5–dione (AMPD).The probe incorporates adjacent dione structures at the pyrene *** selectively interacts with oxygen-rich alkene-labeled drug molecules under ice-blue LED light exposure,producing specific fluorescence emission and enabling in vivo tracking and flow cytometry sorting.A methyl azide group was also introduced at the pyrene core to help efficiently enrich target proteins via click chemistry with alkyne-functionalized *** demonstrates exceptional biocompatibility,rendering it highly suitable for visual photo-triggered tracking *** with metabolic labeling using an oxygen-rich alkene-tagged drug molecule probe,AMPD is effective for live animal,tissue,cellular,and in-gel imaging,as well as target protein identification through magnetic *** its versatile capabilities,AMPD enhances our comprehension of drug-target interactions at the in vivo level and expedites the process of drug discovery.

关键词： Multimodal bioorthogonal probe Bioorthogonal reactions Photoclick Drug tracking

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Alum colloid encapsulated insideβ-glucan particles enhance humoral and CTL immune responses of MUC1 vaccine

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Chinese chemical Letters 2021年第6期32卷 1963-1966页

作者： Yonghui Liu Mingjing Li Haomiao Zhu Zhe Jing Xiaona Yin Kun Wang Zhangyong Hong Wei Zhao state key laboratory of medicinal chemical biology College of Pharmacy and KLMDASR of TianjinNankai UniversityTianjin 300353China state key laboratory of medicinal chemical biology&Tianjin key laboratory of Protein sciences College of Life SciencesNankai UniversityTianjin 300071China

We have developed a MUC1 antigen-based antitumor vaccine loaded on alum colloid encapsulated insideβ-glucan particles(GP-Al).The constructed vaccine induced strong MUC1 antigen specific Ig G antibody titers and enhanced CD^(8+)T cells cytotoxic effect to kill tumor *** results indicated that GP-Al can be served as an efficient delivery system and adjuvant for the development of cancer vaccines especially small molecule antigens based cancer vaccines.

关键词： MUC 1 antigen Glycopeptide GP-Al Adjuvant Antitumor vaccine

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Mechanical Properties and Degradability of Electrospun PCL/PLGA Blended Scaffolds as Vascular Grafts

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Transactions of Tianjin University 2019年第2期25卷 152-160页

作者： Jingchen Gao Siyuan Chen Di Tang Li Jiang Jie Shi Shufang Wang state key laboratory of medicinal chemical biology College of Life SciencesNankai University key laboratory of Bioactive Materials for Ministry of Education College of Life SciencesNankai University

In our study, the mechanical properties and degradability of vascular grafts made from poly(ε-caprolactone)(PCL) and poly(lactic-co-glycolic acid)(PLGA) at different ratios were investigated. The results showed that the electrospun PCL/PLGA grafts possess good mechanical properties and biodegradability. The tensile and burst strength of the scaffolds met the demands of vascular grafts. In vitro degradation tests indicated that the degradation rate of the materials increased with the percentage of PLGA, and in vivo tests showed that increasing the amount of PLGA is an effective way to promote cell infiltration. Particularly, the electrospun PCL/PLGA blended scaffold with 10% PLGA exhibited a balance of mechanical and degradation properties, making it a promising tissue engineering material for vascular grafts.

关键词： Electrospinning Poly(ε-caprolactone) Poly(lactic-co-glycolic acid) Mechanical properties Biodegradability

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