Acta Pharmaceutica Sinica. B最新文献

Preclinical evaluation of a novel tetrazine probe within a pretargeted delivery system for theranostics in HER2-positive tumor-bearing mice models 一种新型四氮探针在her2阳性荷瘤小鼠模型的预先靶向递送系统中的临床前评估。

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-08-01 Epub Date: 2026-03-10 DOI: 10.1016/j.apsb.2026.03.004

Pengcheng Ma, Hui Tan, Qingyu Lin, Yuxia Liu, Hua Shen, Shuhua He, Hongxing Su, Zonghua Luo, Dai Shi, Dengfeng Cheng

{"title":"Preclinical evaluation of a novel tetrazine probe within a pretargeted delivery system for theranostics in HER2-positive tumor-bearing mice models","authors":"Pengcheng Ma, Hui Tan, Qingyu Lin, Yuxia Liu, Hua Shen, Shuhua He, Hongxing Su, Zonghua Luo, Dai Shi, Dengfeng Cheng","doi":"10.1016/j.apsb.2026.03.004","DOIUrl":"10.1016/j.apsb.2026.03.004","url":null,"abstract":"<div><div>The approval of radionuclide therapy strategies in nuclear medicine has revolutionized the treatment landscape for patients with advanced malignancies. Due to significant HER2 overexpression in some solid tumors, radionuclide therapy targeting HER2 is a viable strategy. The traditional monoclonal antibody (mAb) direct radiolabelling system may lead to off-target radiation exposure. To address this limitation, we employed the established inverse-electron demand Diels-Alder (IEDDA)-based pretargeting strategy and designed a novel tetrazine probe. First, we identified the optimal targeting molecule (Pertuzumab) and optimal metabolic time (48 h) through micro-positron emission tomography/computed tomography (PET/CT) scans and biodistribution studies of [<sup>89</sup>Zr]Zr-DFO-Per, [<sup>89</sup>Zr]Zr-DFO-Per-F(ab')<sub>2</sub> and [<sup>89</sup>Zr]Zr-DFO-Per-Fab. Next, TCO-Pertuzumab (TCO-Per) was administered to HER2-overexpressing SKOV3 tumor-bearing mice models, and after 48 h of circulation and clearance, a novel radiolabelled small molecule Tz ([<sup>131</sup>I]I-Tyr-<span>d</span>-peptide-PEG<sub>11</sub>-Tz) was introduced. Through a series of <em>in vivo</em> studies, we observed prolonged retention of [<sup>131</sup>I]I-Tyr-<span>d</span>-peptide-PEG<sub>11</sub>-Tz in SKOV3 tumors with rapid renal clearance, along with promising therapeutic efficacy. Our study demonstrates that the novel tetrazine probe within a pretargeting delivery system overcomes limitations of traditional strategies and shows promise for clinical translation.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 5424-5438"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mussel-inspired biphasic microneedle patch for long-acting hypothyroidism treatment 贻贝启发双相微针贴片治疗长效甲状腺功能减退。

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-08-01 Epub Date: 2026-04-22 DOI: 10.1016/j.apsb.2026.04.012

Wen Zhang, Hanqing Liu, Jinxuan Hou, Kai Lei, Jiapeng Lei, Yinli Jin, Chuang Chen, Jianying Huang, Wei Li

{"title":"Mussel-inspired biphasic microneedle patch for long-acting hypothyroidism treatment","authors":"Wen Zhang, Hanqing Liu, Jinxuan Hou, Kai Lei, Jiapeng Lei, Yinli Jin, Chuang Chen, Jianying Huang, Wei Li","doi":"10.1016/j.apsb.2026.04.012","DOIUrl":"10.1016/j.apsb.2026.04.012","url":null,"abstract":"<div><div>Hypothyroidism, caused by insufficient thyroid hormone production or impaired responsiveness, is typically managed with lifelong daily oral levothyroxine sodium (LT<sub>4</sub>). However, oral administration often suffers from variable gastrointestinal absorption and poor adherence. Here, we report a mussel-inspired biphasic microneedle (MN) patch integrating LT<sub>4</sub> microcrystals and a bioadhesive PDA-PAM hydrogel backing for sustained and patient-friendly hypothyroidism management. The biphasic MNs, composed of rapidly dissolving PVA/sucrose tips and a robust polystyrene base, efficiently deposit LT<sub>4</sub> microcrystals intradermally upon insertion, enabling gradual dissolution and sustained release. The hydrogel backing offered strong and flexible adhesion, ensuring reliable skin attachment during movement. <em>In vitro</em>, the patches exhibited first-order LT<sub>4</sub> release for 9 days. In hypothyroid rats, a single patch application maintained therapeutic plasma LT<sub>4</sub> concentrations for ∼6 days, with bioavailability comparable to intravenous injection. In a preliminary study in healthy volunteers (<em>n</em>= 13), placebo MN patches demonstrated high insertion efficiency, good short-term tolerability, and favorable user acceptability. While further studies are required to establish long-term safety and efficacy in patients with hypothyroidism, these findings support the feasibility of a minimally invasive, extended-interval LT<sub>4</sub> delivery strategy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 5439-5451"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy? hif：肿瘤的主要驱动因素及其在靶向治疗中的分子开关作用？

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-08-01 Epub Date: 2026-06-24 DOI: 10.1016/j.apsb.2026.06.040

Yi Peng, Ying Che, Yingqi Zhao, Zheng Wang, Zhanlei Pei, Yanyun Hu, Yuhang Yin, Xiaolong Pan, Xiaoyun Hu, Minjie Wei, Huizhe Wu

{"title":"HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?","authors":"Yi Peng, Ying Che, Yingqi Zhao, Zheng Wang, Zhanlei Pei, Yanyun Hu, Yuhang Yin, Xiaolong Pan, Xiaoyun Hu, Minjie Wei, Huizhe Wu","doi":"10.1016/j.apsb.2026.06.040","DOIUrl":"10.1016/j.apsb.2026.06.040","url":null,"abstract":"<div><div>Hypoxia-inducible factors (HIFs) serve as the central signaling hub within the hypoxic tumor microenvironment, coordinating tumor proliferation, metastasis, and therapy resistance. This protein family comprises HIF-1<em>α</em>, HIF-2<em>α</em>, HIF-3<em>α</em>, and HIF-1<em>β</em>, with distinct subcellular localization patterns reflecting their isoform-specific oxygen-sensing mechanisms. Tumor-associated HIF expression is regulated through a multifaceted network involving non-coding RNAs (ncRNAs), mitochondrial metabolites, and post-translational modifications (PTMs). These aberrantly expressed HIFs then orchestrate biologically important processes including metabolic reprogramming, angiogenesis, and pro-tumorigenic inflammation. It is important to note that current evidence regarding HIF-3<em>α</em> function remains limited and requires further validation <em>in vivo</em>. This review first systematically deciphers the mechanisms governing HIF dysregulation in tumors, before elucidating the key biological processes involved. We then synthesize advances in HIF-targeting inhibitors. These pivotal findings provide a solid theoretical foundation and novel insights for both anticancer therapies targeting this critical “molecular switch” and translational research focusing on HIFs as promising therapeutic targets.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 4808-4828"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of non-coding RNAs in regulating R-loop dynamics in cancer: Mechanisms and therapeutic implications 非编码rna在癌症中调节r环动力学的作用：机制和治疗意义。

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-08-01 Epub Date: 2026-06-17 DOI: 10.1016/j.apsb.2026.06.030

Sixiang Zheng, Junjie Li, Hong Lin, Xudong Zhang, Fangyi Long, Ting Wang

{"title":"The role of non-coding RNAs in regulating R-loop dynamics in cancer: Mechanisms and therapeutic implications","authors":"Sixiang Zheng, Junjie Li, Hong Lin, Xudong Zhang, Fangyi Long, Ting Wang","doi":"10.1016/j.apsb.2026.06.030","DOIUrl":"10.1016/j.apsb.2026.06.030","url":null,"abstract":"<div><div>R-loops, RNA:DNA hybrids formed during transcription, play critical roles in regulating gene expression and maintaining genome stability. Dysregulation of R-loop formation and resolution has been linked to genomic instability, a hallmark of cancer. Recent advances have highlighted the pivotal role of non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), in modulating R-loop dynamics, influencing tumorigenesis, and contributing to therapeutic resistance. These ncRNAs participate in the formation, stabilization, and resolution of R-loops, which in turn regulate critical processes such as transcriptional regulation, DNA repair, and chromatin architecture. For example, circRNAs such as circSMARCA5 and circDMD have been shown to induce R-loop formation, influencing gene expression and sensitizing cancer cells to chemotherapy. Conversely, lncRNAs such as TUG1 and NEAT1 regulate R-loop resolution, maintaining genome stability and enhancing tumor cell survival. The interaction between ncRNAs and R-loops offers promising avenues for targeted therapeutic strategies aimed at restoring R-loop balance to improve cancer treatment outcomes. This review provides an in-depth exploration of the molecular mechanisms by which ncRNAs modulate R-loop dynamics and discusses their potential as biomarkers and therapeutic targets in oncology. Furthermore, we highlight the challenges and future directions in translating these findings into clinical applications.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 4749-4769"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Telomere-associated non-malignant pulmonary diseases: Pathogenic mechanisms and therapeutic strategies 端粒相关的非恶性肺部疾病：致病机制和治疗策略

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-08-01 Epub Date: 2026-06-21 DOI: 10.1016/j.apsb.2026.06.034

Hongyan Zhan, Ruifang Zheng, Yanyan Li, Xinyu Liu, Yujie Shi, Ruxuan Chen, Qi Hou, Hui Huang, Mingbao Lin

{"title":"Telomere-associated non-malignant pulmonary diseases: Pathogenic mechanisms and therapeutic strategies","authors":"Hongyan Zhan, Ruifang Zheng, Yanyan Li, Xinyu Liu, Yujie Shi, Ruxuan Chen, Qi Hou, Hui Huang, Mingbao Lin","doi":"10.1016/j.apsb.2026.06.034","DOIUrl":"10.1016/j.apsb.2026.06.034","url":null,"abstract":"<div><div>Telomeres and telomerase have been extensively implicated in the cellular processes of aging and inflammation. Recent studies have shown that telomere length (TL), the shelterin complex, and telomerase dysfunction are closely related to non-malignant pulmonary diseases, including interstitial lung diseases (ILD), chronic obstructive pulmonary disease (COPD), and asthma. Short telomere defects with or without mutations in telomere maintenance genes and telomerase are relatively common, affecting the progression of non-malignant pulmonary diseases, explaining disease susceptibility, and revealing clinically relevant manifestations. In this review, we examine the biological characteristics and functions of telomeres and telomerase, and investigate the intricate relationship between changes in TL and mutations in telomerase genes in non-malignant pulmonary diseases after a detailed associated literature review. Subsequently, we focus on the clinical features of non-malignant pulmonary diseases related to dysfunctional telomeres/telomerase, as well as the potential molecular mechanisms underlying these associations, along with the current status of therapeutic interventions. Finally, we delineate current knowledge gaps and transformative opportunities in telomere biology research, with a focus on bridging molecular discoveries to clinical innovations for telomere-associated non-malignant pulmonary diseases, aiming to accelerate the development of precision diagnostic tools and mechanism-based therapeutics.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 4829-4853"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exendin-4 alleviates anxiety-like behaviors in chronic restraint stress mice via regulating BLA GLP-1R/BDNF signaling Exendin-4通过调节BLA GLP-1R/BDNF信号通路减轻慢性约束应激小鼠的焦虑样行为。

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-08-01 Epub Date: 2026-06-01 DOI: 10.1016/j.apsb.2026.05.031

Ke Wei, Meng Yu, Lei Gao, Qiaoyue Zhang, Jianhua Ding, Qian Zhang, Gang Hu

{"title":"Exendin-4 alleviates anxiety-like behaviors in chronic restraint stress mice via regulating BLA GLP-1R/BDNF signaling","authors":"Ke Wei, Meng Yu, Lei Gao, Qiaoyue Zhang, Jianhua Ding, Qian Zhang, Gang Hu","doi":"10.1016/j.apsb.2026.05.031","DOIUrl":"10.1016/j.apsb.2026.05.031","url":null,"abstract":"<div><div>Clinical studies have suggested that exendin-4 (Ex-4) exhibits therapeutic potential for anxiety disorders, yet the molecular mechanisms underlying its efficacy remain largely unclear. Our study demonstrates that Ex-4 at specific doses ameliorates anxiety-like behaviors in mice. Mechanistically, Ex-4 could cross the blood–brain barrier and enter the central nervous system, where it exerts anxiolytic effects by activating glucagon-like peptide-1 receptor (GLP-1R) in the basolateral amygdala (BLA). Anterior dorsal bed nucleus of the stria terminalis (adBNST) as a downstream projection target of BLA neurons. Chemogenomic inhibition of the BLA-adBNST circuit induced anxiety-like phenotypes, which were rescued by Ex-4 treatment. Brain-derived neurotrophic factor (BDNF), a critical neurotrophin implicated in neuropsychiatric disorders including anxiety and depression, was functionally interrogated in this pathway. Furthermore, conditional knockdown of <em>Bdnf</em> in the BLA-adBNST circuit abolished the anxiolytic effects of Ex-4, indicating that the activation of GLP-1R in BLA neurons drives BDNF release into adBNST to mitigate anxiety. Taken together, these studies identify a central mechanism whereby Ex-4 attenuates anxiety-like behaviors by promoting BDNF release in the BLA-adBNST circuit.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 5168-5182"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Universal off-the-shelf TGF-β1-knockout whole-tumor cell vaccine overcomes immunotherapy resistance in pMMR/MSS tumors 通用的现成TGF-β1敲除全肿瘤细胞疫苗克服pMMR/MSS肿瘤的免疫治疗耐药

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-08-01 Epub Date: 2026-06-08 DOI: 10.1016/j.apsb.2026.06.001

Weixiao Yang, Zhexu Dong, Qi Xiong, Yushuang Ren, Lin Zhang, Yi Liu, Jiaqi Han, Tian Tian, Xiaolan Su, Gang Shi, Hongxin Deng

{"title":"Universal off-the-shelf TGF-β1-knockout whole-tumor cell vaccine overcomes immunotherapy resistance in pMMR/MSS tumors","authors":"Weixiao Yang, Zhexu Dong, Qi Xiong, Yushuang Ren, Lin Zhang, Yi Liu, Jiaqi Han, Tian Tian, Xiaolan Su, Gang Shi, Hongxin Deng","doi":"10.1016/j.apsb.2026.06.001","DOIUrl":"10.1016/j.apsb.2026.06.001","url":null,"abstract":"<div><div>Mismatch repair-proficient (pMMR)/microsatellite-stable (MSS) tumors, representing the majority of solid cancers, remain largely unresponsive to immune checkpoint inhibitors, highlighting the urgent need for effective therapeutic strategies. Tumor cell vaccines, serving as delivery platforms for a broad repertoire of tumor antigens, hold potential for eliciting systemic antitumor immunity, yet their clinical efficacy has remained limited. Here, we developed T<em>β</em>1KO/PolyIC-Vac, an off-the-shelf therapeutic whole-tumor cell vaccine generated by CRISPR-Cas9-mediated TGF-<em>β</em>1 knockout and formulated with the TLR3 agonist Poly(I:C). In therapeutic vaccination models, subcutaneous vaccination significantly suppressed distal tumor growth, reduced lung metastases, and delayed spontaneous colorectal tumor progression. It also synergized with anti-PD-1 blockade, enhancing complete response rates and establishing baseline antitumor immunity. Mechanistically, knockout of tumor-derived TGF-<em>β</em>1 reprogrammed immunity by reducing MDSC accumulation to relieve local immunosuppression and activate dendritic cells in draining lymph nodes, while intrinsically triggering the tumor STAT1–IL-15 axis to enhance vaccine immunogenicity. Poly(I:C) further enhanced cross-presentation and adaptive immunity, conferring long-term cross-protection against heterologous tumors. Together, these findings establish T<em>β</em>1KO/PolyIC-Vac as a universal tumor vaccine platform capable of efficiently delivering a comprehensive repertoire of tumor antigens and eliciting robust, durable, and cross-protective tumor-specific immunity in immunotherapy-resistant pMMR/MSS tumors.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 5405-5423"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting NAT10 with Remodelin reshapes the pro-fibrotic microenvironment in renal fibrogenesis via inhibiting exosome oversecretion from tubular cells 用重塑蛋白靶向NAT10，通过抑制小管细胞的外泌体过度分泌，重塑肾纤维化的促纤维化微环境。

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-08-01 Epub Date: 2026-05-22 DOI: 10.1016/j.apsb.2026.05.020

Yuqin Tan, Jiaojiao Zheng, Ruojiao Wang, Zhaozhong Zhong, Suxiang Chen, Shuo Lu, Jiayu Zheng, Yongrong Ye, Ning Na, Tong Zheng

{"title":"Targeting NAT10 with Remodelin reshapes the pro-fibrotic microenvironment in renal fibrogenesis via inhibiting exosome oversecretion from tubular cells","authors":"Yuqin Tan, Jiaojiao Zheng, Ruojiao Wang, Zhaozhong Zhong, Suxiang Chen, Shuo Lu, Jiayu Zheng, Yongrong Ye, Ning Na, Tong Zheng","doi":"10.1016/j.apsb.2026.05.020","DOIUrl":"10.1016/j.apsb.2026.05.020","url":null,"abstract":"<div><div>Renal fibrosis induces irreversible renal failure and lacks therapies. The tubular epithelial cells (TEC) largely depend on exosomes to create a pro-fibrotic microenvironment, initiating fibroblast activation. However, how exosome secretion of TEC is over-activated during renal fibrogenesis remains unknown. Herein, <em>in vitro</em> high-throughout screen uncovered acetyltransferase NAT10 as promising target to interfere with TEC-fibroblast communication. Further experiments showed that NAT10 was upregulated mainly in the TEC of fibrotic kidneys, and its conditional depletion in TEC alleviated renal fibrosis <em>in vivo</em>. Mechanistically, nuclear NAT10 coordinated with cytoplasmic NAT10 to promote exosome secretion of TEC to induce fibroblast activation <em>via</em> combining mRNA ac4C modification and lysine acetylation (Kac). Moreover, NAT10 upregulated the abundance of exosomal Gli in TEC, which were vital for fibroblast activation. In summary, NAT10-mediated orchestration of ac4C and Kac modifications is the mechanism of over-activated exosome secretion of TEC during renal fibrogenesis. And targeting NAT10 with Remodelin is a promising therapy for renal.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 5328-5350"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phase change nanodroplets: Challenges and clinical potential 相变纳米液滴：挑战和临床潜力。

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-08-01 Epub Date: 2026-05-28 DOI: 10.1016/j.apsb.2026.05.030

Xiaoyu Wang, Roman Barmin, Roger Molto Pallares, Anne Rix, Fabian Kiessling

{"title":"Phase change nanodroplets: Challenges and clinical potential","authors":"Xiaoyu Wang, Roman Barmin, Roger Molto Pallares, Anne Rix, Fabian Kiessling","doi":"10.1016/j.apsb.2026.05.030","DOIUrl":"10.1016/j.apsb.2026.05.030","url":null,"abstract":"<div><div>Phase change nanodroplets (PCND) consist of a liquid fluorocarbon core, which vaporizes into gas upon energy excitation, and a stabilizing shell. Through this phase-change property, PCND combine nanoparticle-like stability and pharmacokinetics, such as tissue extravasation and uptake by the mononuclear phagocyte system, with distinctive microbubble-like capabilities, namely ultrasound contrast enhancement and energy-triggered therapeutic action. PCND serve both as highly sensitive imaging agents, from molecular imaging to high-resolution vascular mapping, and as versatile therapeutics, used for example for thrombolysis, tissue ablation, biofilm removal, immunomodulation, and drug delivery. This review article provides a focused review of the biological behavior of PCND, including blood half-life, biodistribution, clearance pathways, and tumor accumulation, following a brief overview of the key physicochemical features that shape their <em>in vivo</em> fate. By comparing data across studies, we identify major inconsistencies in reported pharmacokinetics and highlight critical knowledge gaps, particularly regarding safety data. We further summarize advances in PCND-enabled imaging and therapy, and propose strategies to strengthen formulation design, biological evaluation, and stimulation protocols to support future clinical translation. Overall, PCND hold strong potential as a versatile theranostic platform. Continued systematic and clinically focused research is expected to accelerate their path toward clinical translation.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 8","pages":"Pages 4998-5015"},"PeriodicalIF":14.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metal-drug coordinated nanozymes for ROS scavenging and Kupffer cell polarization to alleviate drug-induced liver injury 金属-药物协同纳米酶清除ROS和Kupffer细胞极化以减轻药物性肝损伤。

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-08-01 Epub Date: 2026-05-15 DOI: 10.1016/j.apsb.2026.05.006

Xiayun Chen, Ziqi Liang, Lichong Lu, Zhouchuan Shao, Wenhui Tang, Yiqi Liu, Jianqiao Li, Baizhong Chen, Enping Lai, Guodong Zheng, Minyan Wei, Shiying Li

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