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Enhanced oral drug delivery by mimicking natural amino acid and oligopeptide absorption route

Nano research 2025年第2期18卷 525-540页

作者： Ruinan Wu Xiaoxing Fan Licheng Wu Liyun Xing Jinxia Kong Zhou Zhou Jingyuan Wen Lian Li Yuan Huang Key laboratory of drug-targeting and drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China School of Pharmacy Faculty of Medical and Health SciencesUniversity of AucklandAuckland 1023New Zealand

Oral delivery of protein and peptide drugs presents considerable challenges due to their susceptibility to digestive enzymes in gastrointestinal(Gl)tract and low efficiency of transepithelial ***,inspired by efficient absorption of protein-based nutrients,we constructed several kinds of oral drug delivery systems by mimicking natural amino acid and oligopeptide absorption *** kinds of amino acids and two kinds of oligopeptides were chosen as targeting ligands to mediate transportation of orally administered nanoparticles(NPs).Liraglutide(Lira),a kind of glucagon like peptide-1(GLP-1)receptor agonist,was used as model *** functionalized NPs could protect Lira from enzymatic degradation in Gl ***,compared with amino acid-modified NPs,oligopeptide-modified NPs exhibited greater transepithelial transport efficiency and were primarily absorbed in the proximal small intestine due to the high expression and transportation mediated by proton coupled oligopeptide transporter 1(PEPT1).These Lira-loaded NPs could effectively control the blood glucose level,reduce plasma lipid level,and repair tissue damage on type 2 diabetic mice and even showed comparable hypoglycemic effects of subcutaneous injection(s.c.)free *** study demonstrates the potential of mimicking natural oligopeptide absorption route to enhance oral delivery of protein and peptide drugs.

关键词： oral drug delivery amino acid absorption route oligopeptide absorption route liraglutide

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Zoledronate-loaded aluminum salt nanovaccines amplify cellular immune response by enhancing cross-presentation

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Nano research 2025年第1期18卷 559-571页

作者： Chunting He Penghui He Xue Tang Shuting Bai Ming Qin Yunting Zhang Zhaofei Guo Guangsheng Du Xun Sun Key laboratory of drug-targeting and drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China

Being a Th2 stimulator,classic aluminum salt-based adjuvants only stimulate weak cellular immune responses that are required for vaccination against intracellular viruses or cancerous *** a thirdgeneration bisphosphonate,zoledronate(ZOL)can enhance antigen crosspresentation by inhibiting key enzymes of the mevalonate ***,we developed the subunit antigen ovalbumin(OVA)and ZOL co-loaded aluminum hydroxide nanoparticles(APN-OVA-ZOL)and investigated their capacity for inducing cellular immune responses against the *** results showed that the developed nanovaccines could successfully encapsulate OVA and ZOL,and enabled efficient lymph node *** by the mevalonate pathway inhibition effect of ZOL,APN-OVA-ZOL significantly promoted *** a result,APN-OVA-ZOL induced robust cellular immunity,including the activation of T and B *** a EG7-OVA tumor-bearing murine model,APN-OVA-ZOL significantly inhibited the tumor growth and prolonged mice *** work provided a strong empirical foundation indicating that zoledronate-loaded aluminum salt nanovaccines had a strong potency for cancer immunotherapy.

关键词： zoledronate(ZOL) mevalonate pathway antigen cross-presentation cellular immune responses

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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China(Life Sciences) 2025年第1期68卷 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China Department of Gastrointestinal cancer Center Peking University Cancer Hospital&InstituteBeijing 100142China Department of Liver Surgery&Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityKey Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032China State Key laboratory of Holistic Integrative Management of Gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China

Extrachromosomal DNA(ecDNA)is a form of circular DNA mostly found in tumor *** the typical chromosomal DNA,ecDNA is circular,self-replicating,and carries complete or partial gene *** ecDNA occurrence remains a rare event in cancer,recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer,implying that ecDNA plays a central role in accelerating tumor *** has also been associated with increased tumor mutation burden,chromosomal instability,and even tumor microenvironment *** may be crucial in influencing tumor heterogeneity,drug sensitivity,oncogenic senescence,and tumor immunogenicity,leading to a worsening prognosis for tumor *** this way,several clinical trials have been conducted to investigate the importance of ecDNA in clinical *** this review,we summarize the biogenesis,characteristics,and current research methods of ecDNA,discuss the vital role of ecDNA-caused tumor heterogeneity in cancers,and highlight the potential role of ecDNA in cancer therapy.

关键词： extrachromosomal DNA cancer therapy tumor heterogeneity drug resistance tumor evolution

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Bifunctional organocatalyst-catalyzed dynamic kinetic resolution of hemiketals for synthesis of chiral ketals via hydrogen bonding control

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Chinese Chemical Letters 2025年第1期36卷 248-252页

作者： Meng Shan Yongmei Yu Mengli Sun Shuping Yang Mengqi Wang Bo Zhu Junbiao Chang State Key laboratory of Antiviral drugs Pingyuan LaboratoryNMPA Key Laboratory for Research and Evaluation of Innovative DrugSchool of Chemistry and Chemical EngineeringHenan Normal UniversityXinxiang 453007China

Herein,we report the dynamic kinetic resolution asymmetric acylation ofγ-hydroxy-γ-perfluoroalkyl butenolides/phthalides catalyzed by amino acid-derived bifunctional organocatalysts,and a series of ketals were obtained in high yields(up to 95%)and excellent enantioselectivities(up to 99%).In terms of synthetic utility,the reaction can be performed on a gram scale,and the product can be converted into potential biological nucleoside analog.

关键词： Bifunctional organocatalyst Dynamic kinetic resolution Hemiketal Chiral ketals Hydrogen bonding

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Chiral phosphoramidite ligand-modulated palladium auto-tandem catalysis for asymmetric dehydrogenative dienylation of imines with α-alkenes

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Science China Chemistry 2025年

作者： Zhong-Sheng Nong Hao-Fan Qian Ying-Chun Chen Pu-Sheng Wang Liu-Zhu Gong Hefei National research Center for Physical Sciences at the Microscale and Department of Chemistry University of Science and Technology of China Key laboratory of drug targeting and drug Delivery System (Sichuan University) Ministry of Education and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University School of Materials and Chemistry Southwest University of Science and Technology

The development of efficient processes allowing rapid access to complex chiral molecules from easily available alkenes is a long-term pursuit in the synthetic chemistry community. Transition metal-catalyzed asymmetric functionalization of allylic C–H bond represents a unique alternative toward this goal. However, enantioselective dehydrogenative transformation of olefins to value-added optically enriched molecules remains yet to be discovered. Here, we report a highly enantioselective dehydrogenative dienylation of imines with unactivated α-alkenes driven by the synergistic action of palladium complex and carboxylic acid. Chiral phosphoramidite ligands turned out to be superior in modulating the performance of palladium autotandem catalysis and allowed a broad range of α-alkenes and imines to be transformed into chiral dienylamines. Mechanistic studies suggest that the dienes could be in situ generated from α-alkenes through a palladium(0)-mediated dehydrogenative process in the presence of excess benzoquinone oxidants, and then participated in the Pd-chiral phosphoramidite-catalyzed intermolecular vinylogous-type addition to the imines activated by the carboxylic acid co-catalyst. Notably, the second β-H elimination occurring in the dienylation event might be the turnover-limiting step.

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N-Benzyl arylamide derivatives as novel and potent tubulin polymerization inhibitors against gastric cancers: Design,structure–activity relationships and biological evaluations

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Chinese Chemical Letters 2025年第2期36卷 256-261页

作者： Jian Song Shenghui Wang Qiuge Liu Xiao Wang Shuo Yuan Hongmin Liu Saiyang Zhang School of Basic Medical Sciences Zhengzhou University Children's Hospital Affiliated to Zhengzhou University Henan Children's Hospital Zhengzhou Children's Hospital School of Pharmaceutical Sciences Institute of Drug Discovery & Development Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education) Zhengzhou University State Key laboratory of Esophageal cancer Prevention & Treatment

In this work,we employed a ring-opening strategy to develop a series of novel N-benzyl arylamide derivatives as tubulin polymerization ***,13n （MY-1388） exhibited remarkable antiproliferative potency on fifteen human cancer cell lines,with half maximal inhibitory concentration (IC50)values ranging from 8 nmol/L to 48 nmol/***,13n effectively suppressed tubulin polymerization by targeting the colchicine-binding site (IC50=0.62μmol/L).13n also exhibited significant inhibition of cell colony formation,as well as displayed potent effects on inducing G2/M phase cell cycle arrest and promoting ***,13n exhibited enhanced and adequate liver microsomal stability in human and rat liver microsomes,and also exhibited a moderate half-life (T1/2=0.938 h) in ***,13n demonstrated effective antitumor effects in vivo in suppressing tumor growth in the MGC-803xenograft model (tumor growth inhibition （TGI） value was 76.4%at the dosage of 30 mg kg-1day-1)with a good safety ***,these results revealed that 13n represents a promising tubulin polymerization inhibitor that deserves further investigation for its efficacy in treating gastric cancers.

关键词： Antiproliferative activities CA-4 Colchicine binding site N-Benzyl arylamide Tubulin

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Towards Improved Steroid Hormone Analysis: The Shift from Immunoassays to Mass Spectrometry

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Journal of Analysis and Testing 2025年第01期 118-135页

作者： Bowen Deng Mengxin Bi Yuanyuan Zheng Dilshad Hussain Sen Yang Di Chen Henan Key laboratory of Nanomedicine for targeting Diagnosis and Treatment Zhengzhou University International Center for Chemical and Biological Sciences HEJ Research Institute of Chemistry University of Karachi

Steroid hormones, synthesized from cholesterol via cytochrome P450 enzymes, are categorized into adrenocortical hormones and sex hormones. Their monitoring is crucial in clinical and research settings for evaluating disease risk and physiological shifts, as well as for managing medical conditions. The structural similarity and concentration differences of steroid hormones in biological samples create significant challenges for analysis. Traditional immunoassays(IAs) are now less effective due to cross-reactivity and other limitations. Advances in mass spectrometry(MS), especially liquid chromatography-tandem mass spectrometry, have become preferred for steroid hormone detection, establishing a new “gold standard” in the field. The paper examines the influence of various pretreatment methods on the sensitivity and detection limits of steroid hormones,including protein precipitation, liquid–liquid extraction, solid-phase extraction, cold-induced phase separation technique,and derivatization technique, providing a crucial reference for clinical steroid detection. This paper reviews IAs and MS methods used recently(2013–2023) for detecting endogenous steroid hormones, highlighting their analytical strengths and limitations. It also discusses recent advancements and future prospects in both IA and MS methodologies.

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Advancements in proteogenomics for preclinical targeted cancer therapy research

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Biophysics Reports 2025年第01期11卷 56-76页

作者： Yuying Suo Yuanli Song Yuqiu Wang Qian Liu Henry Rodriguez Hu Zhou Department of Analytical Chemistry State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences University of Chinese Academy of Sciences Department of Otolaryngology Eye & ENT Hospital Fudan University Office of cancer Clinical Proteomics research National Cancer Institute National Institutes of Health

Advancements in molecular characterization technologies have accelerated targeted cancer therapy research at unprecedented resolution and dimensionality. Integrating comprehensive multi-omic molecular profiling of a tumor, proteogenomics, marks a transformative milestone for preclinical cancer research. In this paper, we initially provided an overview of proteogenomics in cancer research,spanning genomics, transcriptomics, and proteomics. Subsequently, the applications were introduced and examined from different perspectives, including but not limited to genetic alterations, molecular quantifications, single-cell patterns, different post-translational modification levels, subtype signatures,and immune landscape. We also paid attention to the combined multi-omics data analysis and pancancer analysis. This paper highlights the crucial role of proteogenomics in preclinical targeted cancer therapy research, including but not limited to elucidating the mechanisms of tumorigenesis, discovering effective therapeutic targets and promising biomarkers, and developing subtype-specific therapies.

关键词： Proteogenomics Targeted cancer therapy Integrated omics analysis

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Plasma metabolomics combined with mass spectrometry imaging reveals crosstalk between tumor and plasma in gastric cancer genesis and metastasis

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Chinese Chemical Letters 2025年第1期36卷 506-512页

作者： Yanhua Chen Xian Ding Jun Zhou Zhaoying Wang Yunhai Bo Ying Hu Qingce Zang Jing Xu Ruiping Zhang Jiuming He Fen Yang Zeper Abliz Key laboratory of Mass Spectrometry Imaging and Metabolomics(State Ethnic Affairs Commission) Center for Imaging and Systems BiologyCollege of Life and Environmental SciencesMinzu University of ChinaBeijing 100081China State Key laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100050China Key laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational research(Ministry of Education) Center of Drug Clinical TrialPeking University Cancer Hospital and InstituteBeijing 100142China Beijing Engineering research Center of Food Environment and Public Health Minzu University of ChinaBeijing 100081China Key laboratory of Ethnomedicine of Ministry of Education School of PharmacyMinzu University of ChinaBeijing 100081China Key laboratory of Carcinogenesis and Translational research(Ministry of Education) Department of BioBankPeking University Cancer Hospital and InstituteBeijing 100142China Pharmacy Department of Beijing Chao–Yang Hospital Capital Medical UniversityBeijing 100020China

Gastric Carcinoma(GC)is a highly fatal malignant tumor with a poor *** elevated mortality rates are primarily due to its proclivity for late-stage *** the metabolic interactions between tumor microenvironment and the systemic bloodstream could help to clearly understand the mechanisms and identify precise biomarkers of tumor growth,proliferation,and *** this study,an integrative approach that combines plasma metabolomics with mass spectrometry imaging of tumor tissue was developed to investigate the global metabolic landscape of GC tumorigenesis and *** results showed that the oxidized glutathione to glutathione ratio(GSSH/GSH)became increased in non-distal metastatic GC(M0),which means an accumulation of oxidative stress in tumor ***,it was found that the peroxidation of polyunsaturated fatty acids,such as 9,10-EpOMe,9-HOTrE,etc.,were accelerated in both plasma and tumor tissues of distal metastatic GC(M1).These changes were further confirmed the potential effect of CYP2E1 and GGT1 in metastatic potential of GC by mass spectrometry imaging(MSI)and immunohistochemistry(IHC).Collectively,our findings reveal the integrated multidimensional metabolomics approach is a clinical useful method to unravel the bloodtumor metabolic crosstalk,illuminate reprogrammed metabolic networks,and provide reliable circulating biomarkers.

关键词： Metabolomics Spatial-resolved metabolomics Gastric cancer Blood-tumor metabolic crosstalk Lipid peroxidation

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Antimicrobial resistance crisis:could artificial intelligence be the solution?

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Military Medical research 2025年第1期12卷 72-95页

作者： Guang-Yu Liu Dan Yu Mei-Mei Fan Xu Zhang Ze-Yu Jin Christoph Tang Xiao-Fen Liu Department of Immunology and Pathogen Biology School of Basic Medical SciencesHangzhou Normal UniversityKey Laboratory of Aging and Cancer Biology of Zhejiang ProvinceKey Laboratory of Inflammation and Immunoregulation of HangzhouHangzhou Normal UniversityHangzhou 311121China National Key Discipline of Pediatrics Key laboratory of Major Diseases in Children Ministry of Education Laboratory of DermatologyBeijing Pediatric Research InstituteBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijing 100045China Robert and Arlene Kogod Center on aging Mayo ClinicRochesterMN 55905USA Department of Biochemistry and Molecular Biology Mayo ClinicRochesterMN 55905USA Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Sir William Dunn School of Pathology University of OxfordOxford OX13REUK Institute of Antibiotics Huashan HospitalFudan UniversityKey Laboratory of Clinical Pharmacology of AntibioticsNational Health Commission of the People’s Republic of ChinaNational Clinical Research Centre for Aging and MedicineHuashan HospitalFudan UniversityShanghai 200040China

Antimicrobial resistance is a global public health threat,and the World Health Organization(WHO)has announced a priority list of the most threatening pathogens against which novel antibiotics need to be *** discovery and introduction of novel antibiotics are time-consuming and *** to WHO’s report of antibacterial agents in clinical development,only 18 novel antibiotics have been approved since ***,novel antibiotics are critically *** intelligence(AI)has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel ***,we first summarized recently marketed novel antibiotics,and antibiotic candidates in clinical *** addition,we systematically reviewed the involvement of AI in antibacterial drug development and utilization,including small molecules,antimicrobial peptides,phage therapy,essential oils,as well as resistance mechanism prediction,and antibiotic stewardship.

关键词： Antibiotic Artificial intelligence(AI) Clinical development Machine learning(ML) Antimicrobial peptide Phage therapy Antibiotic stewardship

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