Acta Pharmaceutica Sinica. B最新文献_第2页

Anti-CD24 antibody-nitric oxide donor conjugates bearing a self-bioorthogonal cleavable linker 抗cd24抗体-一氧化氮供体偶联物携带自生物正交可切割连接

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.07.037

Jianbing Wu , Tianyue Cheng , Jiajun Xie , Ziyu Qian , Linhua Huang , Xun Yuan , Libang Zhang , Shan Yang , Yihua Zhang , Tonglin Xu , Juan Zhang , Zhangjian Huang

{"title":"Anti-CD24 antibody-nitric oxide donor conjugates bearing a self-bioorthogonal cleavable linker","authors":"Jianbing Wu , Tianyue Cheng , Jiajun Xie , Ziyu Qian , Linhua Huang , Xun Yuan , Libang Zhang , Shan Yang , Yihua Zhang , Tonglin Xu , Juan Zhang , Zhangjian Huang","doi":"10.1016/j.apsb.2025.07.037","DOIUrl":"10.1016/j.apsb.2025.07.037","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed <em>via</em> chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody–drug conjugate (ADC), named <strong>HN03</strong>, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. <strong>HN03</strong> specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. <strong>HN03</strong> also exhibited potent <em>in vitro</em> and <em>in vivo</em> antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 10","pages":"Pages 5366-5386"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229908","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

Spatiotemporally delivery of Cas9 ribonucleoprotein/DNAzyme logic systems using near-infrared upconversion nanomachine for precise immunotherapy 利用近红外上转换纳米机器时空递送Cas9核糖核蛋白/DNAzyme逻辑系统用于精确免疫治疗

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.07.010

Chao Chen , Shiyu Du , Qianglan Lu , Xueting Shen , Shuai Ding , Lihua Qu , Yamei Gao , Zhiqiang Yin , Zhe Li , Yujun Song , Xin Han

{"title":"Spatiotemporally delivery of Cas9 ribonucleoprotein/DNAzyme logic systems using near-infrared upconversion nanomachine for precise immunotherapy","authors":"Chao Chen , Shiyu Du , Qianglan Lu , Xueting Shen , Shuai Ding , Lihua Qu , Yamei Gao , Zhiqiang Yin , Zhe Li , Yujun Song , Xin Han","doi":"10.1016/j.apsb.2025.07.010","DOIUrl":"10.1016/j.apsb.2025.07.010","url":null,"abstract":"<div><div>Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1–PC linker–C2 (C<sub>2</sub>P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn<sup>2+</sup> ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS–STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C<sub>2</sub>P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS–STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 10","pages":"Pages 5431-5443"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229912","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

Progress and challenges of functionalized bacterial encapsulation: A novel biotechnology for next-generation biotherapeutics 功能化细菌包封的进展与挑战：下一代生物治疗的新生物技术

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.07.028

Ying Zhang , Yuwei Wu , Xinyu Zhao , Qinghua Ye , Lulu Cao , Ming Liu , Bao Gao , Qinya Niu , Nuo Chen , Zixuan Duan , Yu Ding , Juan Wang , Moutong Chen , Ying Li , Qingping Wu

{"title":"Progress and challenges of functionalized bacterial encapsulation: A novel biotechnology for next-generation biotherapeutics","authors":"Ying Zhang , Yuwei Wu , Xinyu Zhao , Qinghua Ye , Lulu Cao , Ming Liu , Bao Gao , Qinya Niu , Nuo Chen , Zixuan Duan , Yu Ding , Juan Wang , Moutong Chen , Ying Li , Qingping Wu","doi":"10.1016/j.apsb.2025.07.028","DOIUrl":"10.1016/j.apsb.2025.07.028","url":null,"abstract":"<div><div>The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 10","pages":"Pages 5167-5191"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145230046","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

Discovery of novel radioligand [18F]AZD9574 for selective imaging of PARP1 in the CNS 新放射配体AZD9574在中枢神经系统PARP1选择性成像中的发现[18F]

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.09.021

Xiaoyun Zhou , Kai Chen

引用次数: 0

Discovery of orally active and serine-targeting covalent inhibitors against hCES2A for ameliorating irinotecan-triggered gut toxicity 发现针对hCES2A的口服活性和丝氨酸靶向共价抑制剂，以改善伊立替康引发的肠道毒性

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.08.007

Ya Zhang , Yufan Fan , Yunqing Song , Guanghao Zhu , Xinjuan Li , Jian Huang , Xinrui Guo , Changhai Luan , Dongning Kang , Lu Chen , Zhangping Xiao , Zhaobin Guo , Hairong Zeng , Dapeng Chen , Zhipei Sang , Guangbo Ge

{"title":"Discovery of orally active and serine-targeting covalent inhibitors against hCES2A for ameliorating irinotecan-triggered gut toxicity","authors":"Ya Zhang , Yufan Fan , Yunqing Song , Guanghao Zhu , Xinjuan Li , Jian Huang , Xinrui Guo , Changhai Luan , Dongning Kang , Lu Chen , Zhangping Xiao , Zhaobin Guo , Hairong Zeng , Dapeng Chen , Zhipei Sang , Guangbo Ge","doi":"10.1016/j.apsb.2025.08.007","DOIUrl":"10.1016/j.apsb.2025.08.007","url":null,"abstract":"<div><div>Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed <em>via</em> three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (<strong>B7</strong>) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine <strong>B7</strong> carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, <strong>C3</strong> showed the most potent time-dependent inhibition on hCES2A (IC<sub>50</sub> = 0.56 nmol/L), excellent specificity and favorable drug-like properties. <strong>C3</strong> could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while <strong>C3</strong> emerges as a promising orally active drug candidate for ameliorating ITGT.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 10","pages":"Pages 5312-5326"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229900","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

Nucleic acid-based delivery system delivering platinum drugs cooperates with siRNA for potentiated chemo-immunotherapy by reducing phosphatidylserine exposure and activating the cGAS–STING pathway 基于核酸的铂类药物递送系统通过减少磷脂酰丝氨酸暴露和激活cGAS-STING通路，与siRNA合作进行强化化学免疫治疗

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.07.027

Jianqin Yan , Zijian Zhao , Dengshuai Wei , Huapeng Zheng , Bin He , Yong Sun

{"title":"Nucleic acid-based delivery system delivering platinum drugs cooperates with siRNA for potentiated chemo-immunotherapy by reducing phosphatidylserine exposure and activating the cGAS–STING pathway","authors":"Jianqin Yan , Zijian Zhao , Dengshuai Wei , Huapeng Zheng , Bin He , Yong Sun","doi":"10.1016/j.apsb.2025.07.027","DOIUrl":"10.1016/j.apsb.2025.07.027","url":null,"abstract":"<div><div>Chemotherapeutic drugs, such as cisplatin and phenanthriplatin (PhenPt), as STING agonists to induce DNA damage and activate the cyclic GMP–AMP synthase-stimulator of interferon genes (cGAS–STING) signaling pathway provides a potential strategy for clinical chemo-immunotherapy. However, treatment with Pt-based drugs leads to irreversible ectopia of phosphatidylserine (PS), a major component of the intracellular membrane, to the surface of the cancer cells by enzymes (Xkr8). Exposed PS can bind to immune cell receptors and inhibit the presentation of tumor antigens, leading to immunosuppression and attenuation of chemotherapy. Herein, we report a novel approach to enhance chemo-immunotherapy by constructing siRNA targeted Xkr8 (siXkr8)-mediated tetrahedral framework nucleic acid nanogel structure concurrently loaded with PhenPt (siXkr8-FNG/PhenPt) for co-delivery of siRNA and Pt-based drugs. The results showed that siXkr8-FNG/PhenPt can not only be used as an efficient delivery carrier to deliver siXkr8, block the expression of Xkr8, reduce the exposure of PS on the cancer cells surface, but also act as an immune stimulant to activate cGAS–STING pathway, effectively improve the immunosuppressive microenvironment, produce antitumor immune response, and inhibit tumor growth and metastasis. Overall, this new delivery system is important for improving the effect of Pt-based drug chemotherapy, inducing immune enhancement and nucleic acid drug delivery.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 10","pages":"Pages 5444-5457"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229913","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

Small-sized twin-nanoparticles normalize tumor vasculature to enhance tumor accumulation and penetration for potent eradication of cancer stem-like cells 小尺寸的双纳米颗粒使肿瘤血管系统正常化，促进肿瘤的积累和渗透，从而有效地根除癌症干细胞

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.08.001

Changshun Zhao , Wei Wang , Zhengchun Huang , Yuqing Wan , Rui Xu , Junmei Zhang , Bingbing Zhao , Ke Wang , Suchen Wen , Yinan Zhong , Dechun Huang , Wei Chen

{"title":"Small-sized twin-nanoparticles normalize tumor vasculature to enhance tumor accumulation and penetration for potent eradication of cancer stem-like cells","authors":"Changshun Zhao , Wei Wang , Zhengchun Huang , Yuqing Wan , Rui Xu , Junmei Zhang , Bingbing Zhao , Ke Wang , Suchen Wen , Yinan Zhong , Dechun Huang , Wei Chen","doi":"10.1016/j.apsb.2025.08.001","DOIUrl":"10.1016/j.apsb.2025.08.001","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 10","pages":"Pages 5458-5473"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229915","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

PROTAC-loaded nanocapsules degrading BRD4 for radio-chemotherapy sensitization in glioblastoma 载protac纳米胶囊降解BRD4对胶质母细胞瘤的放化疗增敏

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.03.018

Yun Guo , Mingzhu Fang , Shilin Zhang , Zheng Zhou , Zonghua Tian , Haoyu You , Yun Chen , Jingyi Zhou , Xiaobao Yang , Yunke Bi , Chen Jiang , Tao Sun

{"title":"PROTAC-loaded nanocapsules degrading BRD4 for radio-chemotherapy sensitization in glioblastoma","authors":"Yun Guo , Mingzhu Fang , Shilin Zhang , Zheng Zhou , Zonghua Tian , Haoyu You , Yun Chen , Jingyi Zhou , Xiaobao Yang , Yunke Bi , Chen Jiang , Tao Sun","doi":"10.1016/j.apsb.2025.03.018","DOIUrl":"10.1016/j.apsb.2025.03.018","url":null,"abstract":"<div><div>Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood–brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL<sub>(SS)</sub>P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-<span>l</span>-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL<sub>(SS)</sub>P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 10","pages":"Pages 5050-5070"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229926","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 cutting-edge progress of novel biomedicines in ovulatory dysfunction therapy 新生物医学在排卵功能障碍治疗中的前沿进展

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.08.008

Xuzhi Liang , Shiyu Zhang , Dahai Li , Hao Liang , Yueping Yao , Xiuhong Xia , Hang Yu , Mingyang Jiang , Ying Yang , Ming Gao , Lin Liao , Jiangtao Fan

{"title":"The cutting-edge progress of novel biomedicines in ovulatory dysfunction therapy","authors":"Xuzhi Liang , Shiyu Zhang , Dahai Li , Hao Liang , Yueping Yao , Xiuhong Xia , Hang Yu , Mingyang Jiang , Ying Yang , Ming Gao , Lin Liao , Jiangtao Fan","doi":"10.1016/j.apsb.2025.08.008","DOIUrl":"10.1016/j.apsb.2025.08.008","url":null,"abstract":"<div><div>Ovulatory dysfunction (OD) is one of the main causes of infertility in women of childbearing age, which not only affects their reproductive ability, but also physical and mental health. Traditional treatment strategies have limited efficacies, and the emergence of biomedicines provides a promising alternative solution <em>via</em> the strategies of combining engineered design with modern advanced technology. This review explores the pathophysiological characteristics and related induction mechanisms of OD, and evaluates the current cutting-edge advances in its treatments. It emphasizes the potentials of biomedicines strategies such as hydrogels, nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy. By mimicking natural physiological processes, and achieving controlled drug release, these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming, tissue repair, and metabolic and immune regulation. Despite the promising progress, there are still challenges in terms of biomedical complexity, differences between animal models and human physiology, and the demand for intelligent drug carriers in the therapy of OD. Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration, promoting the development of reproductive regenerative medicine.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 10","pages":"Pages 5145-5166"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145230045","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

Cerium single-atom catalysts-armed Lactobacillus reuteri for multipronged anti-inflammatory/anti-fibrotic therapy of inflammatory bowel disease 铈单原子催化剂武装罗伊氏乳杆菌用于炎症性肠病的多管齐下抗炎/抗纤维化治疗

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-10-01 DOI: 10.1016/j.apsb.2025.06.022

Yinying Pu , Shaorong Huang , Shuang Gao , Yangying Duan , Wenhao Li , Qiyue Li , Han Lin , Kun Zhang , Min Zhou , Wencheng Wu

{"title":"Cerium single-atom catalysts-armed Lactobacillus reuteri for multipronged anti-inflammatory/anti-fibrotic therapy of inflammatory bowel disease","authors":"Yinying Pu , Shaorong Huang , Shuang Gao , Yangying Duan , Wenhao Li , Qiyue Li , Han Lin , Kun Zhang , Min Zhou , Wencheng Wu","doi":"10.1016/j.apsb.2025.06.022","DOIUrl":"10.1016/j.apsb.2025.06.022","url":null,"abstract":"<div><div>Simultaneous management of intestinal mucosal barrier dysfunction and gut microbiota dysregulation represents a significant challenge in the treatment of inflammatory bowel disease (IBD). Herein, we report a novel system that integrates multi-enzyme mimicking cerium single-atom nanocatalysts (CeSACs) with <em>Lactobacillus reuteri</em> probiotics (LR@CeSACs) for multipronged management of IBD. In this system, CeSACs demonstrate robust multi-enzyme activities across a broad pH range, effectively scavenging elevated reactive oxygen species, downregulating pro-inflammatory cytokines, and suppressing the expression of fibrosis-related genes. Moreover, probiotics promote the targeting and retention of the CeSACs for sustained catalytic antioxidant therapy. In turn, the inflammation relief enabled by CeSACs promotes bacterial viability, allowing for the rapid reshaping of intestinal barrier function and the restoration of gut microbiota. Therefore, LR@CeSACs exhibit excellent catalytic anti-inflammatory and anti-fibrotic therapeutic effects, as well as a certain prophylactic effect, as demonstrated in several murine models.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 10","pages":"Pages 5400-5415"},"PeriodicalIF":14.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229910","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