Acta Pharmaceutica Sinica. B最新文献

A neurotensin receptor type 1-derived pepducin acts as a biased allosteric modulator to regulate target receptor function 神经紧张素受体1型衍生肽肽作为偏倚变构调节剂调节靶受体功能

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2025-12-30 DOI: 10.1016/j.apsb.2025.12.043

Rebecca L. Brouillette , Frédérique Lussier , Émile Breault , Nathan Meneboo , Malihe Hassanzadeh , Victoria Tremblay , Magali Chartier , Élora Midavaine , Laurence Ulrich , Jérôme Côté , Véronique Blais , Christine E. Mona , Jean-Michel Longpré , Michel Grandbois , Pierre-Luc Boudreault , Martin Audet , Élie Besserer-Offroy , Philippe Sarret

{"title":"A neurotensin receptor type 1-derived pepducin acts as a biased allosteric modulator to regulate target receptor function","authors":"Rebecca L. Brouillette , Frédérique Lussier , Émile Breault , Nathan Meneboo , Malihe Hassanzadeh , Victoria Tremblay , Magali Chartier , Élora Midavaine , Laurence Ulrich , Jérôme Côté , Véronique Blais , Christine E. Mona , Jean-Michel Longpré , Michel Grandbois , Pierre-Luc Boudreault , Martin Audet , Élie Besserer-Offroy , Philippe Sarret","doi":"10.1016/j.apsb.2025.12.043","DOIUrl":"10.1016/j.apsb.2025.12.043","url":null,"abstract":"<div><div>Pepducins are synthetic membrane-tethered lipopeptides designed to allosterically modulate G protein-coupled receptor (GPCR) signaling. Here, we characterize a series of pepducins targeting the neurotensin receptor type 1 (NTSR1), revealing their complex and multifaceted modulation properties. Using BRET-based biosensors, we show that PP-001, a pepducin derived from NTSR1’s first intracellular loop, preferentially activates G protein over <em>β</em>-arrestin signaling while inhibiting NT binding, NT-induced <em>β</em>-arrestin recruitment, and NTSR1 internalization, thereby acting as biased allosteric agonist and negative allosteric modulator. PP-001 also promotes the formation of both homo- and heteromeric multi-receptor complexes. <em>In vivo</em>, PP-001 elicits potent, sustained hypotensive effects, reversible by the NTSR1 antagonist SR48692. Although the precise mechanism of pepducin-receptor interaction remains unclear, we identify a critical N-terminal RKK motif for PP-001’s biological activity. Finally, thermodenaturation assays using purified NTSR1, combined with mutagenesis and molecular docking, provide evidence for the role of the receptor’s H8 domain in direct pepducin interaction. Together, these findings highlight pepducins as versatile modulators of GPCR function and as valuable pharmacological tools for GPCR-targeted drug development.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2396-2419"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipid-based nanosystems for atherosclerosis treatment: Evolving approaches and novel therapeutic strategies 基于脂质的纳米系统用于动脉粥样硬化治疗：不断发展的方法和新的治疗策略

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2025-11-05 DOI: 10.1016/j.apsb.2025.11.001

Lijun Li , Mengran Guo , Zhangyu Wang , Mingxuan Yu , Dian Cai , Yuqi Xu , Zhi Liu , Can Huang , Zhaohui Jin , Yongmei Xie , Xiangrong Song , Xinxin Zhang

{"title":"Lipid-based nanosystems for atherosclerosis treatment: Evolving approaches and novel therapeutic strategies","authors":"Lijun Li , Mengran Guo , Zhangyu Wang , Mingxuan Yu , Dian Cai , Yuqi Xu , Zhi Liu , Can Huang , Zhaohui Jin , Yongmei Xie , Xiangrong Song , Xinxin Zhang","doi":"10.1016/j.apsb.2025.11.001","DOIUrl":"10.1016/j.apsb.2025.11.001","url":null,"abstract":"<div><div>Atherosclerosis, the leading cause of cardiovascular diseases, has become increasingly prevalent worldwide, driving the need for innovative therapeutic strategies to improve clinical outcomes. Lipid-based nanosystems have emerged as promising drug delivery platforms due to their biocompatibility, versatility, and proven clinical track records. Among them, traditional systems such as liposomes have been extensively applied in atherosclerosis therapy, primarily for their well-established safety profile and their capacity to deliver both hydrophilic and hydrophobic agents. However, emerging research has expanded the scope of lipid-based nanosystems to include lipid nanoparticles, lipoprotein-based nanosystems, cell membrane-coated nanosystems, and so on. These systems have demonstrated great promise in addressing the complex and heterogeneous nature of the disease. This review aims to provide a comprehensive overview of lipid-based nanosystems, from traditional formulations to cutting-edge innovations, and their evolving applications in the treatment of atherosclerosis. We also discuss the challenges associated with the clinical translation of these systems, as well as future prospects for developing more effective and personalized therapeutic strategies. In conclusion, lipid-based nanosystems provide a promising option for atherosclerosis treatment, potentially driving the progress of novel therapeutic strategies.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2153-2173"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GEMap: A comprehensive gene essentiality map for drug discovery GEMap：用于药物发现的综合性基因本质图谱

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2026-02-06 DOI: 10.1016/j.apsb.2026.02.004

Saisai Tian , Yixue Liang , Jinbo Zhang , Weishan Liang , Jinyuan Lu , Jiajia Ren , Bojian Lin , Ruijun Wu , Chengyang Guo , Weidong Zhang

{"title":"GEMap: A comprehensive gene essentiality map for drug discovery","authors":"Saisai Tian , Yixue Liang , Jinbo Zhang , Weishan Liang , Jinyuan Lu , Jiajia Ren , Bojian Lin , Ruijun Wu , Chengyang Guo , Weidong Zhang","doi":"10.1016/j.apsb.2026.02.004","DOIUrl":"10.1016/j.apsb.2026.02.004","url":null,"abstract":"<div><div>Gene essentiality (synonymous with dependency) mapping reveals therapeutic vulnerabilities for intractable oncogenes, yet integrated platforms bridging CRISPR functional genomics with drug discovery remain limited. To address this gap, we developed GEMap, A Gene Essentiality-Guided Platform for Drug Discovery, by combining genome-wide CRISPR-Cas9 essentiality profiles (1912 screens across 1135 cancer cell lines) with multi-omics annotations, drug profiles and drug targets information (20,000+ compounds). GEMap can be used to (1) explore multimodal gene data (Dependency/Expression/CNV/Mutation) across cell lines and tissues; (2) prioritize context-specific therapeutic targets by quantifying differential genetic dependencies in molecularly stratified cancers, such as <em>KRAS</em> mutant-cancers; and (3) discover tailored treatments and drug candidates targeting particular gene using large-scale drug perturbation data and drug physical targets. To the best of our knowledge, GEMap represents the first platform bridging CRISPR-derived genetic dependencies with pharmacological responses and biological networks and establishes an open-access paradigm for accelerating precision oncology against undruggable targets. GEMap is available at <span><span>https://web.biotcm.net/GEMap/</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2299-2316"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FTO-mediated m6A depletion drives prenatal prednisone exposure-induced cortical neurogenesis deficits and long-term anxiety-depression-like behaviors in offspring fto介导的m6A耗损驱动产前强的松暴露诱导的皮质神经发生缺陷和后代长期焦虑抑郁样行为

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2026-01-23 DOI: 10.1016/j.apsb.2026.01.026

Cuiping Qi , Juanjuan Guo , Sen Zhu , Keshu Liu , Yifan Liu , Mingcui Luo , Xiuping Jin , Gaole Dai , Pu Yang , Shouyi Wang , Xiong Chen , Huijun Chen , Hui Wang , Dan Xu

{"title":"FTO-mediated m6A depletion drives prenatal prednisone exposure-induced cortical neurogenesis deficits and long-term anxiety-depression-like behaviors in offspring","authors":"Cuiping Qi , Juanjuan Guo , Sen Zhu , Keshu Liu , Yifan Liu , Mingcui Luo , Xiuping Jin , Gaole Dai , Pu Yang , Shouyi Wang , Xiong Chen , Huijun Chen , Hui Wang , Dan Xu","doi":"10.1016/j.apsb.2026.01.026","DOIUrl":"10.1016/j.apsb.2026.01.026","url":null,"abstract":"<div><div>Prednisone is widely used to treat pregnancy-complicated autoimmune diseases, but the impact of prenatal prednisone exposure (PPE) on offspring neurodevelopment is unclear. Clinical follow-up using the Ages and Stages Questionnaires (ASQ:SE-2 and ASQ-3) revealed a strong association between PPE and neurodevelopmental abnormalities. In a rat model, PPE significantly inhibited the proliferation and differentiation of cortical radial glial cells (RGCs), impairing cortical neurogenesis and leading to anxiety- and depression-like behaviors. Mechanistically, PPE upregulated fat mass and obesity-associated protein (FTO) nuclear recruitment in RGCs, depleting <em>N</em><sup>6</sup>-methyladenosine (m<sup>6</sup>A) modifications and stabilizing <em>Crebbp</em>/<em>Ep3</em>00 mRNA, which activated genes related to cell cycle arrest and neuronal differentiation <em>via</em> histone 3 at lysine 27 acetylation (H3K27ac) modifications. The key role of FTO in PPE-induced neurodevelopmental impairments was confirmed using <em>Ep3</em>00 shRNA, <em>Fto</em> overexpression lentivirus, and a conditional <em>Fto</em> knockout mouse model (<em>Fto</em><sup><em>fl/fl</em></sup>; Nestin-Cre). Notably, early postnatal neuregulin-1 supplementation promoted RGCs proliferation and alleviated behavioral abnormalities.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2375-2395"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generative active learning guided discovery of a tobramycin and ciprofloxacin adjuvant against multidrug-resistant Pseudomonas aeruginosa infections 生成式主动学习指导了妥布霉素和环丙沙星佐剂对抗多重耐药铜绿假单胞菌感染的发现

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2026-02-06 DOI: 10.1016/j.apsb.2026.02.002

Siyu Zhao , Jie Tang , Ziyang Du , Yujie Li , Yingbo Zhou , Wenqian Liu , Xiao Wu , Xibing Hu , Xin Long , Dengchao Lian , Jinglin Xie , Tiantian Xie , Shuo Dai , Daxi He , Jiahui Su , Youfeng Zhu , Yiqun Chang , Junxia Zheng , Jun Liu , Pinghua Sun

{"title":"Generative active learning guided discovery of a tobramycin and ciprofloxacin adjuvant against multidrug-resistant Pseudomonas aeruginosa infections","authors":"Siyu Zhao , Jie Tang , Ziyang Du , Yujie Li , Yingbo Zhou , Wenqian Liu , Xiao Wu , Xibing Hu , Xin Long , Dengchao Lian , Jinglin Xie , Tiantian Xie , Shuo Dai , Daxi He , Jiahui Su , Youfeng Zhu , Yiqun Chang , Junxia Zheng , Jun Liu , Pinghua Sun","doi":"10.1016/j.apsb.2026.02.002","DOIUrl":"10.1016/j.apsb.2026.02.002","url":null,"abstract":"<div><div>Biofilm-mediated resistance in multidrug-resistant (MDR) <em>Pseudomonas aeruginosa</em> infections severely compromise antibiotic efficacy in clinical applications. Antibacterial adjuvants represent a promising strategy to restore antibiotic sensitivity and reduce therapeutic dosages. To identify new antibacterial adjuvants with unique structure and mechanism, we established a generative active learning workflow integrating an in-house compound repository of 725 biofilm inhibitors and a library of potential antibiofilm targets. The most potent compound STY17 was identified with sub-micromolar antibiofilm activity (IC<sub>50</sub> = 0.29 ± 0.01 μmol/L). In clinically isolated MDR <em>Pseudomonas aeruginosa</em>, STY17 significantly inhibited biofilm formation, potently synergized with tobramycin and ciprofloxacin, and suppressed the resistance development of these antibiotics. Furthermore, mechanistic studies indicated that STY17 inhibited succinate dehydrogenase to disrupt biofilm formation. <em>In vivo</em>, STY17 significantly enhanced the antibacterial activity of tobramycin and ciprofloxacin in <em>Galleria mellonella</em> and the mouse wound infection model with favorable safety profiles. These findings validated the utility of machine learning to discover novel antibacterial adjuvants, revealing STY17 as a promising candidate for antibacterial adjuvants against MDR <em>Pseudomonas aeruginosa</em> infections.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2444-2473"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Artificial intelligence for drug delivery: Yesterday, today and tomorrow 人工智能给药：昨天、今天和明天

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2025-09-17 DOI: 10.1016/j.apsb.2025.09.022

Yiyang Wu , Nannan Wang , Ping Xiong , Ruifeng Wang , Jiayin Deng , Defang Ouyang

{"title":"Artificial intelligence for drug delivery: Yesterday, today and tomorrow","authors":"Yiyang Wu , Nannan Wang , Ping Xiong , Ruifeng Wang , Jiayin Deng , Defang Ouyang","doi":"10.1016/j.apsb.2025.09.022","DOIUrl":"10.1016/j.apsb.2025.09.022","url":null,"abstract":"<div><div>The global pharmaceutical drug delivery market is forecasted to grow to USD 2546.0 billion by 2029. The expanding pharmaceutical market urgently needs a more efficient drug research and development paradigm. Artificial intelligence (AI) is revolutionizing drug delivery by offering alternatives to traditional trial-and-error experimental approaches. This review systematically traces the technological evolution from early simple models to current advanced AI algorithms in various applications, ranging from formulation optimization to the prediction of critical formulation parameters and <em>de novo</em> material design. To enhance the reliability of AI applications in drug delivery, we present comprehensive guidelines and “Rule of Five” (Ro5) principles to systematically direct researchers in utilizing AI in formulation development. This “Ro5” includes the following criteria: a formulation dataset containing at least 500 entries, coverage of a minimum of 10 drugs and all significant excipients, appropriate molecular representations for both drugs and excipients, inclusion of all critical process parameters, and utilization of suitable algorithms and model interpretability. The review concludes with insights into emerging trends and future directions, including the utilization of large language models, multidisciplinary collaboration opportunities, talent development, and culture transformation, aimed at facilitating a paradigm shift toward AI-driven drug formulation development.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2068-2092"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the therapeutic potential of cannabidiol in soft tissue wound healing: Delivery strategies and anti-inflammatory pathways 探索大麻二酚在软组织伤口愈合中的治疗潜力：递送策略和抗炎途径

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2025-10-10 DOI: 10.1016/j.apsb.2025.10.001

Arita Dubnika , Inga Jurgelane , Andra Grava-Ceplite , Selay Tornaci , Natalia N. Porfiryeva , Diana Solovyov , Nabanita Saha , Nibedita Saha , Elina Kelle , Dagnija Loca , Ebru Toksoy Öner , Alejandro Sosnik

{"title":"Exploring the therapeutic potential of cannabidiol in soft tissue wound healing: Delivery strategies and anti-inflammatory pathways","authors":"Arita Dubnika , Inga Jurgelane , Andra Grava-Ceplite , Selay Tornaci , Natalia N. Porfiryeva , Diana Solovyov , Nabanita Saha , Nibedita Saha , Elina Kelle , Dagnija Loca , Ebru Toksoy Öner , Alejandro Sosnik","doi":"10.1016/j.apsb.2025.10.001","DOIUrl":"10.1016/j.apsb.2025.10.001","url":null,"abstract":"<div><div>This review explores the molecular and cellular pathways of soft tissue wound healing and the potential therapeutic use of the non-psychotropic cannabinoid cannabidiol (CBD), integrating findings from <em>in vitro</em> and <em>in vivo</em> preclinical studies as well as completed and ongoing clinical trials. It provides a comprehensive summary of the next steps in new CBD-based product development by analyzing current trends in dosage optimization, treatment guidance, delivery systems, ranging from liposomes, microemulsions to hydrogels. Additionally, the review examines clinical trials related to CBD formulations, delivery routes, and participant outcomes, offering a deeper understanding of the mechanisms guiding the activity beyond binding to cannabinoid 1 (CB1) and CB2 receptors. Furthermore, it highlights challenges and future perspectives in CBD formulation studies, presenting both currently studied approaches and emerging possibilities for innovation. Therapeutic potential of CBD has proved itself in the recent years and only regulatory issues and clarity in treatment and delivery routes will limit its widespread use in soft tissue healing.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2174-2195"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted intestinal barrier repair via probiotic-derived engineered outer membrane vesicles: A 3A1M strategy with antioxidant, anti-inflammatory, anti-ferroptotic, and microbiome modulation effects 通过益生菌衍生的工程外膜小泡进行肠道屏障修复：一种具有抗氧化、抗炎、抗铁腐蚀和微生物组调节作用的3A1M策略

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2026-01-28 DOI: 10.1016/j.apsb.2026.01.031

Li Yu , He Zhang , Chengge Shi , Qiang Zhou , Jiayu Li , Bin Lu , Hongyang Lu , Ting Jin , Yinci Zhu , Tianci Zuo , Mengzhu Xu , Mingli Su , Yanmei Zhang , Quazi T.H. Shubhra , Xiaowen Hu , Hui Deng , Xiaojun Cai

{"title":"Targeted intestinal barrier repair via probiotic-derived engineered outer membrane vesicles: A 3A1M strategy with antioxidant, anti-inflammatory, anti-ferroptotic, and microbiome modulation effects","authors":"Li Yu , He Zhang , Chengge Shi , Qiang Zhou , Jiayu Li , Bin Lu , Hongyang Lu , Ting Jin , Yinci Zhu , Tianci Zuo , Mengzhu Xu , Mingli Su , Yanmei Zhang , Quazi T.H. Shubhra , Xiaowen Hu , Hui Deng , Xiaojun Cai","doi":"10.1016/j.apsb.2026.01.031","DOIUrl":"10.1016/j.apsb.2026.01.031","url":null,"abstract":"<div><div>Intestinal barrier disruption, driven by oxidative stress, ferroptosis, immune imbalance, and gut microbiota dysbiosis, plays a crucial role in inflammatory bowel disease (IBD) pathogenesis. Current treatments are often ineffective and cause side effects, emphasizing the need for novel therapies. Here, we have developed an engineered probiotic-derived outer membrane vesicle (OMV), GDO@CM, combining antioxidant gallic acid (GA) and anti-inflammatory H<sub>2</sub>S for targeted intestinal barrier repair. Constructed from <em>Escherichia coli</em> Nissle 1917 (EcN)-derived OMVs, GA and diallyl trisulfide (DATS) are incorporated into the hydrophilic inner cavity and lipid bilayer, respectively, while mannose-decorated chitosan (CM) is electrostatically attached to the OMVs surface, enhancing stability and enabling targeted delivery to damaged colonic lesions. GDO@CM efficiently enters activated immune cells and epithelial cells, where GA scavenges reactive oxygen species and inhibits ferroptosis, while H<sub>2</sub>S amplifies anti-inflammatory effects. OMVs further synergize with GA and DATS to suppress pathogenic bacteria. These combined actions facilitate effective barrier repair and alleviate IBD symptoms. Single-cell RNA sequencing reveals that GDO@CM reduces inflammation, increases the proportion of reparative M2 macrophages and intestinal stem cells, and promotes epithelial cell proliferation <em>via</em> the APP/CD74 axis. Our findings establish GDO@CM as a promising multi-target therapeutic for IBD, offering a novel strategy for intestinal barrier restoration.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2527-2552"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering the biological fate of mRNA-LNP-based biologics: A perspective from tissue to intracellular distribution 解读基于mrna - lnp的生物制剂的生物学命运：从组织到细胞内分布的视角

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2025-11-19 DOI: 10.1016/j.apsb.2025.11.023

Xin Xu , Lili Cui , Yong Zhang , Jingkai Gu

{"title":"Deciphering the biological fate of mRNA-LNP-based biologics: A perspective from tissue to intracellular distribution","authors":"Xin Xu , Lili Cui , Yong Zhang , Jingkai Gu","doi":"10.1016/j.apsb.2025.11.023","DOIUrl":"10.1016/j.apsb.2025.11.023","url":null,"abstract":"<div><div>The remarkable clinical success of mRNA-lipid nanoparticle (mRNA-LNP) vaccines, particularly evidenced by their pandemic-era impact and subsequent 2023 Nobel Prize recognition, has intensified global efforts to expand their application toward therapeutic biologics. Despite showing strong preventive effects, there are still fundamental knowledge gaps in comprehensively defining the hierarchical biological trajectory of mRNA-LNP formulations, which spans from initial systemic exposure, tissue-specific biodistribution, and intracellular delivery to ultimate protein expression dynamics. These unresolved mechanistic questions pose significant constraints on the rational design of next-generation mRNA-LNP therapeutics, which face increased demands for precision dosing, therapeutic efficacy optimization, and enhanced safety profiles. This review discusses the <em>in vivo</em> fate of mRNA-LNP, focusing specifically on blood/tissue/cellular distribution and kinetics/exposure profiles of both intact mRNA-LNP and dissociated components post-administration. It discusses key factors influencing the distribution of expressed protein and summarizes the corresponding research toolkits along with their advantages and disadvantages. Additionally, it compiles strategies to enhance delivery efficacy, tissue tropism, and safety profiles of mRNA-LNP. We anticipate a better understanding of the biological processes and dynamic pattern of mRNA-LNP, which will accelerate the development of next-generation mRNA biologics with predictable safety and delivery efficiency.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 1943-1970"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Astrocytes in predictive processing of emotion: Kir4.1 as precision modulator of social interaction 星形胶质细胞在情绪预测加工中的作用：Kir4.1作为社会互动的精确调节器

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2026-04-17 DOI: 10.1016/j.apsb.2026.03.043

Aakash Basu , Alfred P. Kaye

引用次数: 0