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Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy

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Chinese Chemical Letters 2024年第7期35卷 377-382页

作者： Mengjuan Sun Muye Zhou Yifang Xiao Hailei Tang Jinhua Chen Ruitao Zhang Chunjiayu Li Qi Ya Qian Chen Jiasheng Tu Qiyue Wang Chunmeng Sun NMPA key laboratory for Research and Evaluation of pharmaceutical preparations and excipients China Pharmaceutical UniversityNanjing 210009China state key laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 211198China Department of Pharmaceutics School of PharmacyChina Pharmaceutical UniversityNanjing 211198China Jiangsu Provincial key laboratory of Drug Metabolism and Pharmacokinetics China Pharmaceutical UniversityNanjing 210009China School of pharmaceutical Science Nanjing Tech UniversityNanjing 211816China

Size is one of the most important characteristics of nanoparticles to influence their biodistribution and antitumoral *** with large sizes have difficulty in deep tumor penetration,while small particles are easily removed from tumor tissues due to the high tumor interstitial fluid *** address these issues,an intelligent core-crosslinked polyion complex micelle(cPCM)with a reversibly sizeswitchable feature was engineered in this *** micelles are consisting of methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PLA),mPEG-PLA-(HE)6CC,and mPEG-PLA-(RG)6CC at an optimal mass ratio of 6:1:1 with an antiangiogenic compound,dabigatran etexilate(DE),*** net charge inside the micelles is switchable when exposed to different pH conditions,thereby leading to revisable size-change of ***-loaded micelles(DE@cPCM)can swell and release drugs at the tumor sites with a mildly acidic pH,while they shrink and protect the cargo from leaking into the blood circulation with a neutral *** indicated that DE@cPCM can inhibit tumor angiogenesis in vitro and in vivo,thereby efficiently restraining tumor growth in a 4T1-bearing mouse ***,the sizeswitchable cPCM is a promising nanoplatform for targeting delivery of anticarcinogens into the matrix of tumor tissues.

关键词： Polyion complex micelle Size-switchable Revisable size-change pH response Antiangiogenic cancer

ZnGa_(2)S_(4):an infrared nonlinear optical material with large second-harmonic generation response and wide band gap

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Rare Metals 2024年第1期43卷 395-401页

作者： Chen-Yang Zhang Xiao-Nan Niu Yan-Feng Wei Shu-Xing Zhou Da-Qing Yang Ying Wang Jian Wang Bing-Bing Zhang College of Chemistry and Materials Science Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of EducationState Key Laboratory of New Pharmaceutical Preparations and ExcipientsHebei UniversityBaoding 071002China Hubei key laboratory of Low Dimensional Optoelectronic Materials and Devices Hubei University of Arts and ScienceXiangyang 441053China Hubei Longzhong laboratory Xiangyang 441000China Department of Chemistry and Biochemistry Wichita State UniversityKansas 67260USA

High-performance nonlinear optical(NLO)crystals are crucial devices to convert wavelength of solid-state *** play an indispensable role in the research of infrared NLO *** this work,ternary chalcogenide ZnGa_(2)S_(4) ... 详细信息

关键词： optical nonlinear harmonic

Heterogeneous Catalysis with Metal-Containing Crystalline Porous Materials:Element-and Site-Specific Insights

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CCS Chemistry 2024年第5期6卷 1110-1129页

作者： Yan Li Andrew G.Walsh Peng Zhang Tianjun Zhang state key laboratory of new pharmaceutical preparations and excipients College of Chemistry and Materials ScienceHebei UniversityBaoding 071002 Department of Chemistry Dalhousie UniversityHalifaxNova Scotia B3H 4R2

Metal-containing crystalline porous materials(CPMs)are gaining popularity in heterogeneous catalysis because of their highly crystalline and porous systems,and their excellent chemical *** of the metal species and framework structure permits them to have greater activity,selectivity,and stability over other *** in-depth understanding of the complex nature of metal active sites in CPMs is essential for revealing the structure-performance relationships and directing the rational design of such *** to conventional characterization techniques,the rapid development of X-ray absorption spectroscopy(XAS)has provided element-and site-specific deep insights into the electronic and structural information of metal species in *** such,this review begins by summarizing novel XAS techniques and analysis methods in accurately obtaining such ***,the combination of XAS with other high-level characterization methods into disclosing the configuration of active sites in metalcontaining CPMs is ***,the utilization of theory-assisted XAS data analysis in examining complex metal-containing CPM catalysts is ***,advanced in-situ/operando XAS studies into revealing the working sites in metal-containing CPMs under catalytic conditions are *** conclude by outlining the future challenges and prospects of XAS measurements,data analyses,and in-situ/operando setups in advancing the study of metal-in-CPM catalysts.

关键词： X-ray absorption spectroscopy in-situ metal species crystalline porous materials heterogeneous catalysis

Z-scheme Bi4O5Br2/NH2-MIL-125（Ti） heterojunctions enable exceptional visible photocatalytic degradation of organic pollutant

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Rare Metals 2024年第7期43卷 3161-3172页

作者： Feng Huang Muhammad Humayun Gang Li Ting-Ting Fan Wen-Lin Wang Yu-Lin Cao Anton Nikiforov Chun-Dong Wang Jing Wang key laboratory of Analytical Science and Technology of Hebei Province Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of EducationState Key Laboratory of New Pharmaceutical Preparations and ExcipientsCollege of Chemistry and Materials ScienceHebei University Energy Water and Environment LabCollege of Humanities and SciencesPrince Sultan University Baoding Green Yijia Environmental Protection Technology Ltd Physics laboratory Industrial Training CenterShenzhen Polytechnic University Department of Applied Physics Ghent University School of Integrated Circuits Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and Technology

One key strategy to enhance photocatalytic performance is to improve the transfer and separation efficiency of photogenerated carriers by building optimized ***,novel Bi4O5Br2/NH2-MIL-125（Ti）Z-scheme heterojunctions are fabricated and used as photocatalysts for organic pollutant *** NH2-MIL-125（Ti） nanosheets are exfoliated via a self-developed alkali solution stripping approach and then uniformly decorated on *** as-prepared Bi4O5Br2/NH2-MIL-125（Ti） presents more than 90% degradation of various pollutants,outperforming the counterpart individual *** various characterization results suggest that the enhanced degradation rate is due to the more intimate face-to-face interfacial contact of the lamellar Z-scheme heterojunction materials,in which the migration path of carriers from the material's interior to the surface can be reduced,in turn enhancing migration efficiency and separation capability significantly.A possible photocatalytic reaction mechanism is proposed based on the photoelectric behaviors,radical trapping experiments and liquid chromatography mass spectrometry *** work promotes the development of new photocatalytic materials for heterojunctions with face-to-face interfacial contacts,as well as the effective purification of wastewater in environmental remediation.

关键词： Z-scheme heterojunctions Photocatalysis Alkaline solution stripping Bi 4 O 5 Br 2 NH 2 -MIL-125(Ti)

The p38/MAPK pathway as a therapeutic target to prevent therapeutic escape of breast cancer stem cells

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Science China Life Sciences 2024年第09期 1867-1880页

作者： Weixiao Yan Xiaotong Wang Wenjing Wang Qi Guo Na Huang Hao Chen Xing-Jie Liang Yu Han Dandan Liu Jinchao Zhang state key laboratory of new pharmaceutical preparations and excipients key laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education College of Chemistry and Materials Science Chemical Biology Key Laboratory of Hebei Province Hebei University CAS key laboratory for Biological Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology

Cancer stem cells(CSCs) play an important role in metastasis development, tumor recurrence, and treatment resistance, and are essential for the eradication of cancer. Currently, therapies fail to eradicate CSCs due to their therapeutic stress-induced cellular escape, which leads to enhanced aggressive behaviors compared with CSCs that have never been treated. However, the underlying mechanisms regulating the therapeutic escape remain unknown. To this end, we established a model to isolate the therapeutic escaped CSCs(TSCSCs) from breast CSCs and performed the transcription profile to reveal the mechanism. Mechanistically, we demonstrated that the behavior of therapeutic escape was regulated through the p38/MAPK signaling pathway, resulting in TSCSCs exhibiting enhanced motility and metastasis. Notably,blocking the p38/MAPK signaling pathway effectively reduced motility and metastasis ability both in vitro and in vivo, which were further supported by downregulated motility-related genes and epithelial-mesenchymal transition(EMT)-related proteins vimentin and *** obtained findings reveal the p38/MAPK pathway as a potential therapeutic target for TSCSCs and would provide profound implications for cancer therapy.

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Nanomedicine integrating the lipidic derivative of 5-fluorouracil,miriplatin and PD-L1 si RNA for enhancing tumor therapy

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Chinese Chemical Letters 2024年第6期35卷 385-391页

作者： An Lu Yuhao Guo Yi Yan Lin Zhai Xiangyu Wang Weiran Cao Zijie Li Zhixia Zhao Yujie Shi Yuanjun Zhu Xiaoyan Liu Huining He Zhiyu Wang Jian-Cheng Wang Beijing key laboratory of Molecular Pharmaceutics and new Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Tianjin key laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China Department of Immuno-oncology The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011China Department of Pharmacy Clinical Trial Research CenterChina-Japan Friendship HospitalBeijing 100029China laboratory of innovative formulations and pharmaceutical excipients Ningbo Institute of Marine MedicinePeking UniversityNingbo 315832China

Immunosuppressive microenvironments present critical problems in clinical *** regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)with chemotherapeutics has been applied *** this study,miriplatin(MiPt),the lipidic derivative of 5-fluorouracil(Fu-OA),as well as the programmed death ligand 1(PD-L1)target si RNA(siPD-L1)were integrated into Lip-Pt/Fu@siPD-L1 nanoparticles(NPs)for *** vitro results showed that Lip-Pt/Fu@siPD-L1 NPs could exhibit effective siRNA gene silencing and promote the phagocytosis of tumor cells by ***,in vivo results revealed that LipPt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of Mi Pt,5-fluorouracil,and Lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor efficiency of Lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of Mi Pt and siPD-L1 based on the inhibition of CD47 expression and the downregulation of PD-L1 in tumor cells,which elicited a robust anti-tumor immune response through the activation of macrophage phagocytosis and immune checkpoint *** Lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.

关键词： Chemo-immunotherapy Immune checkpoint inhibition Gene silencing Miriplatin Macrophage phagocytosis Nanotechnology

Oral peptide therapeutics for diabetes treatment: state-of-the-art and future perspectives

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2006-2025页

作者： Bingwen Ding Zhu Zhu Cong Guo Jiaxin Li Yong Gan Miaorong Yu state key laboratory of Drug Research and Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China School of Pharmacy Henan UniversityKaifeng 475004China NMPA key laboratory for Quality Research and Evaluation of pharmaceutical excipients National Institutes for Food and Drug ControlBeijing 100050China

Diabetes,characterized by hyperglycemia,is a major cause of death and disability ***,such as insulin and glucagon-like peptide-1(GLP-1)analogs,have shown promise as treatments for diabetes due to their ability to mimic or enhance insulin's actions in the *** to subcutaneous injection,oral administration of anti-diabetic peptides is a preferred ***,biological barriers significantly reduce the efficacy of oral peptide *** advancements in drug delivery systems and formulation techniques have greatly improved the oral delivery of peptide therapeutics and their efficacy in treating *** review will highlight(1)the benefits of oral anti-diabetic peptide therapeutics;(2)the biological barriers for oral peptide delivery,including pH and enzyme degradation,intestinal mucosa barrier,and biodistribution barrier;(3)the delivery platforms to overcome these biological ***,the review will discuss the prospects in this *** information provided in this review will serve as a valuable guide for future developments in oral anti-diabetic peptide therapeutics.

关键词： Oral peptides Diabetes Delivery platforms Insulin Glucagon-like peptide-1 Biodistribution Biological barriers Targeted delivery

Worm-like micelles facilitate the intestinal mucus diffusion and drug accumulation for enhancing colorectal cancer therapy

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Chinese Chemical Letters 2024年第6期35卷 427-432页

作者： Yihan Zhou Duo Gao Yaying Wang Li Liang Qingyu Zhang Wenwen Han Jie Wang Chunliu Zhu Xinxin Zhang Yong Gan state key laboratory of Drug Research and Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China University of Chinese Academy of Sciences Beijing 100049China NMPA key laboratory for Quality Research and Evaluation of pharmaceutical excipients National Institutes for Food and Drug ControlBeijing 100050China School of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai 201203China

Local delivery of nanoparticles holds promise for colorectal cancer(CRC)***,the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby adversely affecting treatment *** is crucial to develop efficient drug delivery carriers that can effectively overcome mucus barriers to treat colorectal ***,we utilized poly(1,4-butadiene)-b-poly(ethylene oxide)polymers to prepare four distinct geometries of polymeric micelles,namely linear micelles(LMs),worm-like micelles(WLMs),large spherical micelles(LSMs),and small spherical micelles(SSMs)to investigate the influence of shape effects on overcoming colonic mucosal *** found that the carriers exhibited diverse shapes while maintaining comparable physicochemical *** these,WLMs had an aspect ratio similar to segmented filamentous bacteria,which exhibited superior mucus penetration ability,leading to prolonged drug release kinetics and faster entry into epithelial cells compared to ***,rectally administrated 10-hydroxycamptothecin-loaded WLMs traversed the colorectal mucus in orthotopic CRC nude mice model,penetrated and accumulated within tumor tissue,and effectively aggregated within cancer cells,thereby inducing significantly robust antitumor outcomes in *** findings underscore the significance of shape design in overcoming colonic mucosal absorption barriers,offering a novel approach for the development of drug delivery carriers tailored for effective tumor therapy.

关键词： Worm-like micelles Mucus penetration Shape dependent Transmucosal delivery Colorectal cancer

Azocalixarenes: a scaffold of universal excipients with high efficiency

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Science China Chemistry 2024年第5期67卷 1697-1706页

作者： Yu-Xin Yue Yi-Lin Lin Meng-Meng Chen Han-Wen Tian Rong Ma Ze-Han Wang Fang-Yuan Chen Yu-Chen Pan Dong-Sheng Guo College of Chemistry State Key Laboratory of Elemento-Organic ChemistryKey Laboratory of Functional Polymer Materials(Ministry of Education)Frontiers Science Center for New Organic MatterCollaborative Innovation Center of Chemical Science and Engineering(Tianjin)Nankai UniversityTianjin 300071China

excipients are important components of pharmaceutical preparations that affect their quality, safety, and efficacy. Macrocyclic receptors are a family of supramolecular excipients with several advantages, including molecular-level protection, small sizes,fast kinetics of host-guest recognition, and modular construction. With the continuous advances in the medical field, personalized and precision medicine requires the development of excipients with low dosages, integrated modifying effects, universality,and controlled release. To meet these requirements, we have developed a new family of macrocyclic excipients based on calixarenes by integrating their covalent(broad chemical design space) and noncovalent(wide range of substrates) ***, azocalixarenes(Azo CAs) were designed, showing high binding affinities to a broad spectrum of active pharmaceutical ingredients(APIs), selectivity to interferents, and responsiveness to hypoxic microenvironments. Due to their highly efficient and controllable recognition, Azo CAs serve as low-dose excipients for 30 APIs. Molecular encapsulation by Azo CAs results in the integrated modification of the physicochemical properties of APIs, including solubility, stability, bioavailability,and biocompatibility. Moreover, Azo CAs can be reduced by azoreductases overexpressed in hypoxic microenvironments,leading to the controlled release of APIs. Collectively, Azo CA excipients have broad application prospects for a series of diseases such as enteritis, arthritis, stroke, cancer, bacterial infection and kidney injury, with diverse therapeutic modalities,including chemotherapy, photodynamic therapy, photothermal therapy, immunotherapy, boron neutron capture therapy, radiotherapy, fluorescence imaging, and their combinations.

关键词： supramolecular chemistry host-guest systems excipient calixarene molecular recognition