Acta Pharmaceutica Sinica. B最新文献_第4页

Cannabidiol alleviates methamphetamine addiction via targeting ATP5A1 and modulating the ATP–ADO–A1R signaling pathway 大麻二酚通过靶向ATP5A1和调节ATP-ADO-A1R信号通路来缓解甲基苯丙胺成瘾

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.08.011

Sha Jin , Cong Lin , Peipei Li , Xue Wang , Yibo Wang , Cong Zhang , Xuenan Wang , Yinghua Peng , Haohong Li , Yuyuan Lu , Xiaohui Wang

{"title":"Cannabidiol alleviates methamphetamine addiction via targeting ATP5A1 and modulating the ATP–ADO–A1R signaling pathway","authors":"Sha Jin , Cong Lin , Peipei Li , Xue Wang , Yibo Wang , Cong Zhang , Xuenan Wang , Yinghua Peng , Haohong Li , Yuyuan Lu , Xiaohui Wang","doi":"10.1016/j.apsb.2025.08.011","DOIUrl":"10.1016/j.apsb.2025.08.011","url":null,"abstract":"<div><div>Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 <em>via</em> the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO–A1R signaling pathway.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 10","pages":"Pages 5261-5276"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229821","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

Imaging poly(ADP-ribose) polymerase-1 (PARP1) in vivo with 18F-labeled brain penetrant positron emission tomography (PET) ligand 用18f标记的脑渗透正电子发射断层扫描（PET）配体在体内成像聚（adp -核糖）聚合酶-1 （PARP1）

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.05.020

Xin Zhou , Jiahui Chen , Jimmy S. Patel , Wenqing Ran , Yinlong Li , Richard S. Van , Mostafa M.H. Ibrahim , Chunyu Zhao , Yabiao Gao , Jian Rong , Ahmad F. Chaudhary , Guocong Li , Junqi Hu , April T. Davenport , James B. Daunais , Yihan Shao , Chongzhao Ran , Thomas L. Collier , Achi Haider , David M. Schuster , Steven H. Liang

{"title":"Imaging poly(ADP-ribose) polymerase-1 (PARP1) in vivo with 18F-labeled brain penetrant positron emission tomography (PET) ligand","authors":"Xin Zhou , Jiahui Chen , Jimmy S. Patel , Wenqing Ran , Yinlong Li , Richard S. Van , Mostafa M.H. Ibrahim , Chunyu Zhao , Yabiao Gao , Jian Rong , Ahmad F. Chaudhary , Guocong Li , Junqi Hu , April T. Davenport , James B. Daunais , Yihan Shao , Chongzhao Ran , Thomas L. Collier , Achi Haider , David M. Schuster , Steven H. Liang","doi":"10.1016/j.apsb.2025.05.020","DOIUrl":"10.1016/j.apsb.2025.05.020","url":null,"abstract":"<div><div>Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood–brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its <sup>18</sup>F-isotopologue ([<sup>18</sup>F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and <em>in vivo</em> PET imaging evaluations in non-human primates, demonstrates the capacity of [<sup>18</sup>F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [<sup>18</sup>F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 10","pages":"Pages 5036-5049"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229925","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

Divergent activation patterns of BRS3 revealed by two Chinese herb-derived agonists 两种中草药衍生激动剂揭示BRS3的不同激活模式

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.06.025

Jie Li , Changyao Li , Qingtong Zhou , Wei Han , Mingzhu Fang , Youwei Xu , Yiting Mai , Yao Zhang , Jiahua Cui , H. Eric Xu , Yan Zhang , Wanchao Yin , Ming-Wei Wang

{"title":"Divergent activation patterns of BRS3 revealed by two Chinese herb-derived agonists","authors":"Jie Li , Changyao Li , Qingtong Zhou , Wei Han , Mingzhu Fang , Youwei Xu , Yiting Mai , Yao Zhang , Jiahua Cui , H. Eric Xu , Yan Zhang , Wanchao Yin , Ming-Wei Wang","doi":"10.1016/j.apsb.2025.06.025","DOIUrl":"10.1016/j.apsb.2025.06.025","url":null,"abstract":"<div><div>Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3–G<sub>q</sub> complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 10","pages":"Pages 5231-5243"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229914","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

The toxic components, toxicological mechanism and effective antidote for Gelsemium elegans poisoning 秀丽隐杆线虫中毒的毒性成分、毒理机制及有效解毒剂

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-09-01 DOI: 10.1016/j.apsb.2025.07.016

Niping Li , Yaorong Yang , Shengyuan Zhang , Bin Jiang , Wei Zhang , Haibo Wang , Lixin Chen , Liwei Wang , Yiyi Li , Lei Shi , Wencai Ye , Lei Wang

{"title":"The toxic components, toxicological mechanism and effective antidote for Gelsemium elegans poisoning","authors":"Niping Li , Yaorong Yang , Shengyuan Zhang , Bin Jiang , Wei Zhang , Haibo Wang , Lixin Chen , Liwei Wang , Yiyi Li , Lei Shi , Wencai Ye , Lei Wang","doi":"10.1016/j.apsb.2025.07.016","DOIUrl":"10.1016/j.apsb.2025.07.016","url":null,"abstract":"<div><div><em>Gelsemium elegans</em> (<em>G. elegans</em>) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. <em>G. elegans</em> poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of <em>G. elegans</em>, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure–toxicity relationship of <em>Gelsemium</em> alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (<strong>1</strong>), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (<strong>1</strong>) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA<sub>A</sub> receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA<sub>A</sub> receptor antagonists successively reversed action potential firing in gelsenicine (<strong>1</strong>)-treated VRG neurons. Importantly, the GABA<sub>A</sub> receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of <em>G. elegans</em> toxicity, and should assist the development of effective emergency treatments for <em>G. elegans</em> poisoning.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4872-4885"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108348","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

KRAS mutant colon cancer-targeted induction of ferroptosis via photocatalytic activation of BiVO4-embedded silica nano with cascadic downregulation of GPX4/xCT axis 通过光催化激活bivo4包埋二氧化硅纳米并级联下调GPX4/xCT轴，KRAS突变体结肠癌靶向诱导铁凋亡

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-09-01 DOI: 10.1016/j.apsb.2025.06.024

Yixin Jiang , Ratchapol Jenjob , Dahee Ryu , Zheyu Shen , Su-Geun Yang

{"title":"KRAS mutant colon cancer-targeted induction of ferroptosis via photocatalytic activation of BiVO4-embedded silica nano with cascadic downregulation of GPX4/xCT axis","authors":"Yixin Jiang , Ratchapol Jenjob , Dahee Ryu , Zheyu Shen , Su-Geun Yang","doi":"10.1016/j.apsb.2025.06.024","DOIUrl":"10.1016/j.apsb.2025.06.024","url":null,"abstract":"<div><div>Kirsten rat sarcoma virus (<em>KRAS</em>) is a common oncogene in human cancers. Approximately 40% of the patients diagnosed with colorectal cancer (CRC) have <em>KRAS</em> mutations that exhibit strong resistance to targeted molecular therapy and EGFR antibody treatment. In this study, we present photocatalytic silica nanoparticles (A6-FS/BiVO<sub>4</sub> DMSNs) for targeted therapy of <em>KRAS</em> mutant CRC with the induction of cascadic ferroptosis events. Dendritic mesoporous silica nanoparticles (DMSNs) were impregnated with photocatalytic BiVO<sub>4</sub>, loaded with ferroptotic agents (benzoyl ferrocene: B and sorafenib: S), and encoded with CD44-targeting A6 peptides. For the targeting design, we observed CD44 overexpression in <em>KRAS</em> mutant CRC cells using CPTAC data analysis. Upon laser irradiation, A6-FS/BiVO<sub>4</sub> DMSNs generate electron–hole pairs (e<sup>−</sup>/h<sup>+</sup>), which produce hydroxyl radical (OH<sup>·</sup>) and superoxide anions (O<sub>2</sub><sup>·</sup><sup>−</sup>). Laser irradiation simultaneously initiates the dissociation of iron (Fe<sup>2+</sup>) from benzoyl ferrocene and the release of sorafenib. This cascade induces ferroptosis in <em>KRAS</em> mutant CRC cells, especially under conditional inhibition of redox-regulating proteins (cystine/glutamate antiporter and glutathione peroxidase 4), and significantly inhibits tumor growth in a <em>KRAS</em> mutant CRC xenograft animal model.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4932-4944"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108381","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

Yeast-two-hybrid based high-throughput screening to discover SARS-CoV-2 fusion inhibitors by targeting the HR1/HR2 interaction 基于酵母-双杂交的高通量筛选发现针对HR1/HR2相互作用的SARS-CoV-2融合抑制剂

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-09-01 DOI: 10.1016/j.apsb.2025.06.029

Jing Zhang , Dongsheng Li , Wenwen Zhou , Chao Liu , Peirong Wang , Baoqing You , Bingjie Su , Keyu Guo , Wenjing Shi , Tin Mong Timothy Yung , Richard Yi Tsun Kao , Peng Gao , Yan Li , Shuyi Si

{"title":"Yeast-two-hybrid based high-throughput screening to discover SARS-CoV-2 fusion inhibitors by targeting the HR1/HR2 interaction","authors":"Jing Zhang , Dongsheng Li , Wenwen Zhou , Chao Liu , Peirong Wang , Baoqing You , Bingjie Su , Keyu Guo , Wenjing Shi , Tin Mong Timothy Yung , Richard Yi Tsun Kao , Peng Gao , Yan Li , Shuyi Si","doi":"10.1016/j.apsb.2025.06.029","DOIUrl":"10.1016/j.apsb.2025.06.029","url":null,"abstract":"<div><div>The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction <em>in vitro</em> and inhibits SARS-CoV-2-S-mediated cell–cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4829-4843"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108346","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

Cover Story 封面故事

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-09-01 DOI: 10.1016/S2211-3835(25)00541-6

引用次数: 0

Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects 基于脑卒中进展时间轴的缺血性脑卒中和干预策略：回顾与展望

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-09-01 DOI: 10.1016/j.apsb.2025.07.026

Anning Xu , Honghua Zhang , Yihua Zhang , Jianbing Wu , Zhangjian Huang

{"title":"Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects","authors":"Anning Xu , Honghua Zhang , Yihua Zhang , Jianbing Wu , Zhangjian Huang","doi":"10.1016/j.apsb.2025.07.026","DOIUrl":"10.1016/j.apsb.2025.07.026","url":null,"abstract":"<div><div>Ischemic stroke (IS), a leading cause of morbidity and mortality worldwide, primarily results from blood clot formation in cerebral vessels, leading to vessel occlusion, reduced cerebral blood flow, and subsequent tissue ischemia. While thrombolytic therapies and mechanical thrombectomy remain cornerstone treatments for restoring blood flow, their clinical efficacy is significantly limited by the narrow therapeutic window, which underscores the critical need for novel, safe, and effective therapeutic strategies. In this review, we present an intensive analysis of four pathophysiological stages of IS progression and their intervention targets, and evaluate both established and emerging therapeutic strategies with the molecular mechanisms underpinning these methods, aiming to enhance the understanding of IS intervention. Additionally, we discuss current challenges in IS therapy, emphasizing the importance of timely, stage-specific approaches to optimize therapeutic outcomes. Finally, we highlight some promising research directions and innovations to advance IS field.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4543-4581"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108383","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

Chemical and genetic molecular glues to degrade CoREST corepressors 化学和遗传分子胶降解CoREST辅抑制因子

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-09-01 DOI: 10.1016/j.apsb.2025.07.006

Ying-Qi Song , Qingjun Li , Chunquan Sheng

引用次数: 0

A novel dual-targeting strategy of nanobody-driven protein corona modulation for glioma therapy 纳米体驱动蛋白电晕调节治疗胶质瘤的一种新的双靶向策略

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-09-01 DOI: 10.1016/j.apsb.2025.07.014

Yupei Zhang , Shugang Qin , Tingting Song , Zhiying Huang , Zekai Lv , Yang Zhao , Xiangyu Jiao , Min Sun , Yinghan Zhang , Guang Xie , Yuting Chen , Xuli Ruan , Ruyue Liu , Haixing Shi , Chunli Yang , Siyu Zhao , Zhongshan He , Hai Huang , Xiangrong Song

{"title":"A novel dual-targeting strategy of nanobody-driven protein corona modulation for glioma therapy","authors":"Yupei Zhang , Shugang Qin , Tingting Song , Zhiying Huang , Zekai Lv , Yang Zhao , Xiangyu Jiao , Min Sun , Yinghan Zhang , Guang Xie , Yuting Chen , Xuli Ruan , Ruyue Liu , Haixing Shi , Chunli Yang , Siyu Zhao , Zhongshan He , Hai Huang , Xiangrong Song","doi":"10.1016/j.apsb.2025.07.014","DOIUrl":"10.1016/j.apsb.2025.07.014","url":null,"abstract":"<div><div>Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood–brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a “Hitchhiking Effect” mechanism, facilitating efficient <em>trans</em>-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 9","pages":"Pages 4917-4931"},"PeriodicalIF":14.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108258","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