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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

Unlocking the potential of bispecific ADCs for targeted cancer therapy

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Frontiers of Medicine 2024年第4期18卷 597-621页

作者： Hongye Zeng Wenjing Ning Xue Liu Wenxin Luo Ningshao Xia State Key laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamen361102China National institute of diagnostics and Vaccine Development in Infectious Diseases State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsNational Innovation Platform for Industry-Education Integration in Vaccine Researchthe Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical SciencesXiamen UniversityXiamen361102China

Antibody–drug conjugates(ADCs)are biologically targeted drugs composed of antibodies and cytotoxic drugs connected by *** innovative compounds enable precise drug delivery to tumor cells,minimizing harm to normal tissues and offering excellent prospects for cancer ***,monoclonal antibody-based ADCs still present challenges,especially in terms of balancing efficacy and *** antibodies are alternatives to monoclonal antibodies and exhibit superior internalization and selectivity,producing ADCs with increased safety and therapeutic *** this review,we present available evidence and future prospects regarding the use of bispecific ADCs for cancer treatment,including a comprehensive overview of bispecific ADCs that are currently in clinical *** offer insights into the future development of bispecific ADCs to provide novel strategies for cancer treatment.

关键词： antibody-drug conjugate bispecific antibody bispecific ADC cancer

Variation in the Composition of the Essential Oil of Commercial Salvia officinalis *** Samples from Different Countries

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Phyton-International Journal of Experimental Botany 2024年第8期93卷 2051-2062页

作者： Ain Raal Anne Orav Tetiana Ilina Alla Kovalyova Taras Koliadzhyn Yuliia Avidzba Oleh Koshovyi institute of Pharmacy Faculty of MedicineUniversity of TartuTartu50411Estonia institute of Chemistry Tallinn University of TechnologyTallinn12618Estonia The Department of Pharmaceutical Management Drug Technology and PharmacognosyIvano-Frankivsk National Medical UniversityIvano-Frankivsk76018Ukraine The Department of Pharmacognosy National University of PharmacyKharkiv61002Ukraine The Department of clinical laboratory diagnostics Kharkiv National Medical UniversityKharkiv61022Ukraine

Salvia officinalis L.(Lamiaceae)leaves and its essential oil is used for mouth and throat disorders,skin disorders,minor wounds,and gastrointestinal disorders,and is widely used *** research aimed to conduct a comparative study of the composition of *** essential oils from commercial samples,and their main *** volatile constituents from *** leaves were investigated using gas chromatography(GC).The commercial samples of sage leaves were obtained from retail pharmacies in nine mainly European *** yield of essential oil in *** commercial leaves was between 10.0 and 24.8 mL/*** principal components(>5%)among the main identified 25 compounds were 1,8-cineole(8.3%–45.3%),α-thujone(3.0%–34.0%),сamphor(11.3%–29.3%),β-thujone(1.5%–12.9%),viridiflorol(1.1%–10.4%),camphene(2.6%–7.1%),andα-pinene(1.3%–5.8%).In seven(Estonia,England,France,Hungary,Belgium,Ukraine,Georgia)samplesα-thujone *** samples(Estonia,Georgia,England,Hungary)belong to the most common chemotypeα-thujone>camphor>1,*** chemotypes of *** essential oils have been *** thujones are widespread compounds among them.

关键词： Sage terpenoids chemotypes thujone toxicity

Triterpenoids-templated self-assembly nanosystem for biomimetic delivery of CRISPR/Cas9 based on the synergy of TLR-2 and ICB to enhance HCC immunotherapy

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3205-3217页

作者： Bing-Chen Zhang Chun-Mei Lai Bang-Yue Luo Jing-Wei Shao Fujian Provincial Key laboratory of Cancer Metastasis Chemoprevention and Chemotherapy College of ChemistryFuzhou UniversityFuzhou 350116China Department of laboratory Medicine Dongguan Institute of Clinical Cancer Researchthe Tenth Affiliated Hospital of Southern Medical University(Dongguan People’s Hospital)Dongguan 523058China College of Materials and chemical Engineering MinjiangUniversityFuzhou350108China

Combination immunotherapy has shown promising potential for enhancing the objective response rate compared to immune checkpoint blockade(ICB)***,combination therapy with multi-drugs is limited by the different properties of the agents and inconsistent synergistic targeted ***,based on a universal triterpene template and the anticancer active agent ursolic acid(UA),a cytomembrane-coated biomimetic delivery nanoplatform(UR@M)prepared by the selfassembly of a PD-L1 targeted CRISPR/Cas9 system and UA was designed for hepatocellular carcinoma(HCC)***@M showed enhanced tumor accumulation in vivo with homologous tumor targeting,and CRISPR in the nanosystem exhibited potent gene-editing efficiency of 76.53% in vitro and 62.42% in vivo with no off-target *** activated the natural immune system through the TLR-2-MyD88-TRAF6 pathway,which synergistically enhanced the proliferation of natural killer cells and dendritic cells and realized excellent immune cytotoxic T cell infiltration by combining with the ICB of *** strategy of work along both lines based on innate immune and adaptive immunity displayed a significant effect in tumor ***,the UA-templated strategy“killed three birds with one stone”by establishing a self-assembly nanosystem,inducing tumor cell death,and promoting synergistic immunostimulation for HCC treatment.

关键词： Ursolic acid Self-assembly Biomimetic nanoplatform Hepatocellular carcinoma CRISPR/Cas9 Immune checkpoint blockade Gene therapy Immunotherapy

Evaluating the tumor stratification with a lysosomal pH sensitive-probe by fluorescence lifetime imaging

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Chinese chemical Letters 2024年第3期35卷 262-267页

作者： Jun Yan Xing Liang Qian Zhang Luolin Wang Weiying Lin Guangxi Key laboratory of Electrochemical Energy Materials Institute of Optical Materials and Chemical BiologySchool of Chemistry and Chemical EngineeringGuangxi UniversityNanning 530004China

Owing to the anaerobic metabolism in the tumor,abundant acidic metabolites are produced and accumulated in the ***,the cells in different tumor layers are directly linked to the pH ***,due to the lack of robust tools,the high-efficient evaluation of the acidic micro-environment of tumor stratification faces the challenge of accurate *** designed a new pH sensitive fluorescent lifetime probe target to *** we expected,the fluorescence lifetime of PLN possesses a good linear fit to the pH value,which could detect the pH change at a single lysosome level in real time,and then evaluate the different acidity of tumor *** probe PLN is successfully used to evaluate the tumor stratification by fluorescence lifetime imaging microscopy(FLIM)for the first time,which is of great significance in the preoperative diagnosis of clinical tumor treatment or evaluation of drug delivery effect.

关键词： FLIM pH Fluorescence imaging Lysosome Tumor imaging

Recent Advances in Pd-Catalyzed Reactions Involving the “On-Water” Mechanism

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Chinese Journal of Chemistry 2024年第5期42卷 533-542页

作者： Dong Wei Guo-Qiang Lin State Key laboratory of Systems Medicine for Cancer Shanghai Cancer InstituteShanghai Key Laboratory of Systems Regulation and Clinical Translation for CancerRen Ji HospitalShanghai Jiao Tong University School of MedicineShanghai200127 China State Key laboratory of chemical Biology Shanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai200032 China

As the chemical industry grapples with the need for more eco-friendly practices,the use of water as a reaction medium is gaining attraction in organic *** mini-review delves into Pd-catalyzed reactions that utilize the "on-water" mechanism,spanning from 2019 to late *** reactions are neatly categorized into several types: (A) Catalytic C—H activations,(B) Mizoroki- Heck-type reactions,(C) Suzuki-Miyaura reactions,and (D) Cyclization *** showcasing the potential of water as a sustainable reaction medium for organic transformations,these reactions leave no doubt about the importance of embracing eco-friendly practices in the chemical *** Scientists In 1980,a seminal work by Breslow et *** an acceleration of reaction rate in the Diels-Alder *** and co-workers noted a significant increase in the rate of the [2σ+2σ+2π] cycloaddition of quadricyclane and dimethyl azodicarboxylate (DMAD) when the reaction was conducted in water,as opposed to when it was carried out in organic *** term "on-water" was then coined to describe this *** strategy was further expanded to transition-metal catalyzed transformations by Ackermann in ***,Varma and Leazer disclosed a Pd-catalyzed Mizoroki-Heck type arylation of alkenes with diaryliodonium salts “on-water”.The enantioselective version of "on-water" process was not realized until 2014 by the Zhou *** on,the Schaub group described a Pd-catalyzed Suzuki–Miyaura coupling reaction of electron-poor aryl chlorides with water,using only 50 ppm of catalyst *** recently,Liu and Lin extended the "on-water" strategy to Pd-catalyzed double Mizoroki-Heck *** mini-review has focused on Pd-catalyzed reactions involving the “on-water” mechanism.

关键词： Pd-catalyzed “On-water” Green chemistry Aqueous reactions Mechanism Methodology and reactions Mizoroki-Heck reaction Cross-coupling

Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma

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Oncology Research 2024年第4期32卷 679-690页

作者： XINFENG ZHANG SHUANG LI MEIRU SONG YUE CHEN LIANGZHENG CHANG ZHERUI LIU HONGYUAN DAI YUTAO WANG GANGQI YANG YUN JIANG YINYING LU The PLA 307 clinical College of Anhui medical University The Fifth Clinical Medical College of Anhui Medical UniversityHefei230032China Liver Tumor Diagnosis and Research Center 5th Medical Center of the PLA General HospitalBeijing100039China Department of Infection Diseases Guizhou Medical UniversityGuiyang550025China 4302 clinical medical School Peking UniversityBeijingChina Cell and Gene Therapy Innovation Center Beijing Lotuslake BiomedicalScience and Technology ParkBeijing102206China State Key laboratory of chemical Oncogenomics and the institute of Biopharmaceutical and Health Engineering(iBHE) Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China

Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality *** and recurrence primarily contribute to the high mortality rate of liver *** carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and ***,the efficacy of FAK phosphorylation inhibitors is currently ***,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC *** study examined the correlation between FAK expression and the prognosis of ***,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor *** expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying *** results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in *** expression of E-cadherin and decreased expression of vimentin indicated that EMT was ***,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

关键词： Hepatocellular carcinoma(HCC) Focal adhesion kinase(FAK) Proteolytic targeting chimera technology(PROTAC) Epithelial-mesenchymal transformation(EMT) Metastasis

First-line penpulimab(an anti-PD1 antibody)and anlotinib(an angiogenesis inhibitor)with nab-paclitaxel/gemcitabine(PAAG)in metastatic pancreatic cancer:a prospective,multicentre,biomolecular exploratory,phase II trial

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2960-2969页

作者： Huizi Sha Fan Tong Jiayao Ni Yi Sun Yahui Zhu Liang Qi Xiaoqin Li Wei Li Yan Yang Qing Gu Xing Zhang Xiaoxuan Wang Chan Zhu Dongsheng Chen Baorui Liu Juan Du The Comprehensive Cancer Center Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing University&Clinical Cancer Institute of Nanjing UniversityNanjingChina The Comprehensive Cancer Center Nanjing Drum Tower HospitalClinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingChina Department of Oncology The Affiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology The First Affiliated Hospital of Soochow UniversitySuzhouChina Department of Oncology The Affiliated Jiangning Hospital of Nanjing Medical UniversityNanjingChina National institute of Healthcare Data Science at Nanjing University NanjingChina State Key laboratory of Neurology and Oncology Drug Development Jiangsu Simcere Diagnostics Co.Ltd.Nanjing Simcere Medical Laboratory Science Co.Ltd.NanjingChina

Metastatic pancreatic cancer(mPC)has a dismal ***,we conducted a prospective,multicentre,single-arm,phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine(PAAG)in patients with first-line mPC(NCT05493995).The primary endpoints included the objective response rate(ORR)and disease control rate(DCR),while secondary endpoints encompassed progression-free survival(PFS),overall survival(OS),and *** 66 patients analysed for efficacy,the best response,indicated by the ORR,was recorded at 50.0%(33/66)(95%CI,37.4–62.6%),with 33 patients achieving partial response(PR).Notably,the DCR was 95.5%(63/66,95%CI,87.3–99.1%).The median PFS(mPFS)and OS(mOS)were 8.8(95%CI,8.1–11.6),and 13.7(95%CI,12.4 to not reached)months,*** 3/4 treatment-related adverse events(TRAEs)were reported in 39.4%of patients(26/66).In prespecified exploratory analysis,patients with altered SWI/SNF complex had a poorer ***,low serum CA724 level,high T-cell recruitment,low Th17 cell recruitment,and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable *** conclusion,PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for *** biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.

关键词： CA724 prospective centre

Bi-doped carbon quantum dots functionalized liposomes with fluorescence visualization imaging for tumor diagnosis and treatment

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Chinese chemical Letters 2024年第4期35卷 414-419页

作者： Peide Zhu Yangjia Liu Yaoyao Tang Siqi Zhu Xinyang Liu Lei Yin Quan Liu Zhiqiang Yu Quan Xu Dixian Luo Juncheng Wang State Key laboratory of Heavy Oil Processing China University of Petroleum-BeijingBeijing 102249China Department of laboratory Medicine Dongguan Institute of Clinical Cancer ResearchAffiliated Dongguan HospitalSouthern Medical UniversityDongguan 523058China Department of laboratory Medicine Huazhong University of Science and Technology Union Shenzhen Hospital(Nanshan Hospital)Shenzhen 518052China institute of Stomatology First Medical CenterChinese PLA General HospitalBeijing 100853China

Liposomes are one of the significant classes of antitumor nanomaterials and the most successful nanomedicine drugs in clinical translation. However, it is difficult to accurately reveal liposome delivery modes and drug release rates at different p H values to assess the biodistribution and drug delivery pathways in vivo. Here, we established a strategy to integrate Bi-doped carbon quantum dots(CQDs)with liposomes to produce fluorescence visualization and therapeutic effects, namely lipo/Bi-doped ***/Bi-doped CQDs show good water solubility and physicochemical properties, which can be used for in vitro labeling of colon cancer(CT26) cells and in vivo imaging localization tracking tumors for monitoring. Simultaneously, thanks to the excellent p H sensitivity and ion doping characteristic of Bi-doped CQDs, lipo/Bi-doped CQDs can be used to reveal the drug release rate of liposomes at different p H values and exhibit potential effects in vivo antitumor therapy.

关键词： Bi-doped CQDs Lipo/Bi-doped CQDs pH sensitivity In vitro/in vivo imaging Diagnosis and treatment integration