Asian Journal of Pharmaceutical Sciences最新文献

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A novel mRNA nanovaccine with dual immunoregulation ameliorates rheumatoid arthritis and associated pneumonia 一种具有双重免疫调节的新型mRNA纳米疫苗改善类风湿关节炎和相关肺炎
IF 11.9 1区 医学
Asian Journal of Pharmaceutical Sciences Pub Date : 2026-02-01 Epub Date: 2026-01-10 DOI: 10.1016/j.ajps.2026.101120
Jingjing Su , Wenguang Huang , Wenying Zhang , Ziyi Wang , Hongzhou Gu , Pengchao Sun , Yongxing Zhao
{"title":"A novel mRNA nanovaccine with dual immunoregulation ameliorates rheumatoid arthritis and associated pneumonia","authors":"Jingjing Su ,&nbsp;Wenguang Huang ,&nbsp;Wenying Zhang ,&nbsp;Ziyi Wang ,&nbsp;Hongzhou Gu ,&nbsp;Pengchao Sun ,&nbsp;Yongxing Zhao","doi":"10.1016/j.ajps.2026.101120","DOIUrl":"10.1016/j.ajps.2026.101120","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) as a systemic autoimmune disease, frequently triggers various extra-articular symptoms, particularly the RA-associated pneumonia. Unfortunately, the RA-associated pneumonia has garnered insufficient attention, and conventional RA therapies may exacerbate pneumonia-related complications, thereby complicating the treatment process. Herein, a novel dual immunoregulatory mRNA nanovaccine (MPDA@RC@HM) is designed for the efficient treatment of RA and RA-associated pneumonia simultaneously. This innovative mRNA nanovaccine represents a highly organized nanostructure that integrates the rapamycin-loaded mesoporous polydopamine (MPDA) with mRNA encoding the epitope of type Ⅱ collagen, and the surface is modified with hyaluronic acid and dendritic cell membrane. After intravenous injection into collagen-induced arthritis mice, the mRNA nanovaccine exhibits effective distribution and transfection within the spleen and lung, subsequently exerting potent immunoregulation in both organs, thereby yielding a dual therapeutic effect. This study presents a versatile mRNA nanovaccine platform for the treatment of autoimmune diseases and provides an innovative approach for addressing RA and RA-associated pneumonia.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"21 1","pages":"Article 101120"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098727","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
From bench to bedside: Unveiling the background and benefits of nanovaccines tested in clinics 从实验室到床边:揭示纳米疫苗在临床试验的背景和益处
IF 11.9 1区 医学
Asian Journal of Pharmaceutical Sciences Pub Date : 2026-02-01 Epub Date: 2026-01-09 DOI: 10.1016/j.ajps.2026.101116
Vera S. Egorova , Ekaterina P. Kolesova , Maya V. Voronina , Evgenya R. Denisova , Anastasiia O. Syrocheva , Tatiana Pallaeva , Mazdak G. Hakemi , Andrey A. Zamyatnin , Konstantin I. Ivanov , Dmitry Kostyushev , Sergey Brezgin , Anastasiia Kostyusheva , Alessandro Parodi
{"title":"From bench to bedside: Unveiling the background and benefits of nanovaccines tested in clinics","authors":"Vera S. Egorova ,&nbsp;Ekaterina P. Kolesova ,&nbsp;Maya V. Voronina ,&nbsp;Evgenya R. Denisova ,&nbsp;Anastasiia O. Syrocheva ,&nbsp;Tatiana Pallaeva ,&nbsp;Mazdak G. Hakemi ,&nbsp;Andrey A. Zamyatnin ,&nbsp;Konstantin I. Ivanov ,&nbsp;Dmitry Kostyushev ,&nbsp;Sergey Brezgin ,&nbsp;Anastasiia Kostyusheva ,&nbsp;Alessandro Parodi","doi":"10.1016/j.ajps.2026.101116","DOIUrl":"10.1016/j.ajps.2026.101116","url":null,"abstract":"<div><div>Despite the growing body of literature on nanovaccines, focused analyses of platforms tested in and undergoing clinical investigation remain limited. This review addresses this gap by critically examining recent advancements and highlighting nanovaccine technologies that have undergone human clinical trials. Using an extensive search on <span><span>clinicaltrials.org</span><svg><path></path></svg></span>, we explored the diverse applications of nanovaccines, including leading SARS-CoV-2 candidates and platforms targeting other infectious diseases and cancers. We also highlighted foundational research that has enabled clinical investigation of nanovaccines over the past decade, highlighting their potential to address a range of medical conditions. While many technologies have been developed to combat SARS-CoV-2, several key innovations targeted a broader spectrum of diseases. This review details these technologies, focusing on their materials and mechanisms of action in inducing immune protection, while also exploring how nanomedicine facilitates nanovaccine development and introduces novel adjuvant concepts. Finally, we provided a retrospective analysis of the development journey of these platforms, offering insights into the intellectual and technological efforts behind their clinical translation. By bridging the gap between research and application, this review aims to give readers a comprehensive understanding of how nanovaccines progress from the laboratory to clinical practice.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"21 1","pages":"Article 101116"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147385413","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 evolution of lipid nanoparticles: Paving the way for next-generation nucleic acid medicines 脂质纳米颗粒的进化:为下一代核酸药物铺平道路
IF 11.9 1区 医学
Asian Journal of Pharmaceutical Sciences Pub Date : 2026-02-01 Epub Date: 2026-01-21 DOI: 10.1016/j.ajps.2026.101121
Xuan Lin , Hongguang Xiang , Jiong Wu , Ruixi Liao , Yuhao Li , Bohui Xu , Ying Xu , Yan Shen , Qian Li , Yu Tian
{"title":"The evolution of lipid nanoparticles: Paving the way for next-generation nucleic acid medicines","authors":"Xuan Lin ,&nbsp;Hongguang Xiang ,&nbsp;Jiong Wu ,&nbsp;Ruixi Liao ,&nbsp;Yuhao Li ,&nbsp;Bohui Xu ,&nbsp;Ying Xu ,&nbsp;Yan Shen ,&nbsp;Qian Li ,&nbsp;Yu Tian","doi":"10.1016/j.ajps.2026.101121","DOIUrl":"10.1016/j.ajps.2026.101121","url":null,"abstract":"<div><div>Nucleic acid-based therapies have emerged as promising strategies for the regulation of gene expression and the production of therapeutic antigens or proteins for a series of diseases, including cancers, rare diseases, and infectious diseases. However, their clinical application faces challenges. These include high molecular weight, limited cellular uptake, and susceptibility to enzymatic degradation by nucleases <em>in vivo</em>. Both viral and non-viral delivery vectors have been developed as a means of addressing these limitations, including lipid nanoparticles (LNPs), exosomes, polymers, and inorganic nanoparticles. Among these, LNPs have garnered significant attention due to their superior biocompatibility, high delivery efficiency and customizable design potential, as demonstrated by the clinical success of the FDA-approved siRNA drug Onpattro®. The critical role of nucleic acid drug carriers is discussed in this review. It also outlines the major types of carriers under development and examines the advancements and applications in LNP-based systems for nucleic acid delivery. By conducting a review of recent advancements in LNP design, delivery mechanisms, and clinical applications, this article aims to clarify the ways in which LNPs overcome delivery barriers, compare LNPs with other carriers, and identify key trends that can inform the development of next-generation LNP platforms for nucleic acid therapeutics.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"21 1","pages":"Article 101121"},"PeriodicalIF":11.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147385428","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 frontier of oral nanomedicine in colorectal cancer therapy: Folate-targeted 5FU-Nisin-Selenium conjugates and probiotic-rich diets as a novel approach 探索口服纳米药物在结直肠癌治疗中的前沿:叶酸靶向5fu - nisin -硒缀合物和富含益生菌的饮食是一种新方法
IF 11.9 1区 医学
Asian Journal of Pharmaceutical Sciences Pub Date : 2025-12-01 Epub Date: 2025-11-22 DOI: 10.1016/j.ajps.2025.101106
Mozhgan Derakhshan-sefidi , Bita Bakhshi , Aliakbar Rasekhi , Roya Saeidnejad
{"title":"Exploring the frontier of oral nanomedicine in colorectal cancer therapy: Folate-targeted 5FU-Nisin-Selenium conjugates and probiotic-rich diets as a novel approach","authors":"Mozhgan Derakhshan-sefidi ,&nbsp;Bita Bakhshi ,&nbsp;Aliakbar Rasekhi ,&nbsp;Roya Saeidnejad","doi":"10.1016/j.ajps.2025.101106","DOIUrl":"10.1016/j.ajps.2025.101106","url":null,"abstract":"<div><div>This study aimed to assess the therapeutic potential of nisin, 5-fluorouracil (5FU) and selenium encapsulated in folate-conjugated thiolated chitosan nanoparticles (N/5FU/Se@FTCsNPs), combined with a probiotic cocktail of <em>Lactobacillus acidophilus</em> and <em>Bifidobacterium bifidum</em>, against colorectal cancer (CRC). The nanoparticles (277 nm, +9.2 mV) exhibited high drug loading efficiencies (5FU: 89.11 %, nisin: 70.68 %) and pH-responsive release, with minimal drug release under gastric conditions and ∼60.7 % release at colonic pH, facilitating targeted delivery. The formulation remained stable for over 40 d at −20 °C and 4 °C, demonstrating excellent biocompatibility (&lt;2 % hemolysis) and exhibiting strong mucoadhesive and mucus-penetrating abilities. <em>In vitro</em>, N/5FU/Se@FTCsNPs selectively targeted CT26 colon cancer cells (IC₅₀: 1.57 µg/ml) with minimal effects on healthy cells, enhanced cellular uptake, and induced ROS-mediated apoptosis. <em>In vivo</em>, oral administration—especially with probiotics—significantly reduced tumor volume, improved survival rates and alleviated chemotherapy-related side effects such as diarrhea and weight loss. Biodistribution studies confirmed increased tumor targeting and decreased off-target exposure. Mechanistically, the treatment downregulated oncogenes and inflammatory markers (2- to 12.5-fold), including <em>β-catenin, mTOR, COX-2</em> and <em>VEGF-α</em>, while upregulating tumor suppressors and protective genes (4 to 14.8 fold), such as <em>PTEN, CASP9</em> and <em>Mucin 2</em> (<em>P</em> &lt; 0.0001). This indicates inhibition of proliferation, metastasis, inflammation, and angiogenesis, along with improved gut barrier function. Cytokine profiling and histological analysis further confirmed reduced systemic inflammation and maintained hematological safety. These findings highlight N/5FU/Se@FTCsNPs combined with probiotics as a promising, safe and effective oral therapy for CRC, leveraging microbiota modulation and targeted delivery.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 6","pages":"Article 101106"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691629","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
Integrating CRISPR/Cas technology with clinical trials: Principles, progress and challenges CRISPR/Cas技术与临床试验的整合:原理、进展与挑战
IF 11.9 1区 医学
Asian Journal of Pharmaceutical Sciences Pub Date : 2025-12-01 Epub Date: 2025-05-28 DOI: 10.1016/j.ajps.2025.101068
Piao Yang , Mohadeseh Khoshandam , Iman Bhia , Sevil Raji , Hossein Soltaninejad , Saman Hosseinkhani , Mehdi Sani , Amir Ali Hamidieh , Mohsen Sheykhhasan
{"title":"Integrating CRISPR/Cas technology with clinical trials: Principles, progress and challenges","authors":"Piao Yang ,&nbsp;Mohadeseh Khoshandam ,&nbsp;Iman Bhia ,&nbsp;Sevil Raji ,&nbsp;Hossein Soltaninejad ,&nbsp;Saman Hosseinkhani ,&nbsp;Mehdi Sani ,&nbsp;Amir Ali Hamidieh ,&nbsp;Mohsen Sheykhhasan","doi":"10.1016/j.ajps.2025.101068","DOIUrl":"10.1016/j.ajps.2025.101068","url":null,"abstract":"<div><div>CRISPR represent a groundbreaking genome-editing technology that has revolutionized genetic modification. This innovative tool offers an unparalleled revolution in the future treatment of genetic disorders, neurological diseases, infectious diseases and cancer. Despite the rapid expansion of CRISPR applications, its clinical use in humans is still relatively limited, with only 69 active clinical trials and 6 completed studies reported so far. This review examined current clinical trials and their processes in addressing various diseases via the CRISPR/Cas system. While earlier literatures have focused mainly on delivery methods and materials for CRISPR/Cas9, our review emphasized innovative targeting conditions and approaches for novel and functional therapeutic designs. In addition, we reviewed recent research to increase the efficiency of CRISPR editing in the management of genetic disorders and cancer, while exploring their future challenges and potential. This review provided a unique perspective on the advancement of CRISPR technology. By addressing these aspects, we aim to contribute to ongoing efforts to improve CRISPR-based therapies and expand their clinical applications, ultimately striving to transform the future of medical treatment.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 6","pages":"Article 101068"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622883","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
Biomaterials-mediated sequential drug delivery: Emerging trends for wound healing 生物材料介导的顺序给药:伤口愈合的新趋势
IF 11.9 1区 医学
Asian Journal of Pharmaceutical Sciences Pub Date : 2025-12-01 Epub Date: 2025-08-25 DOI: 10.1016/j.ajps.2025.101088
Yuchuan Shi , Shuaichen Guo , Jiayi Tian , Xi Xie , Jie Shi , Xing Zhang , Chenchao Wang
{"title":"Biomaterials-mediated sequential drug delivery: Emerging trends for wound healing","authors":"Yuchuan Shi ,&nbsp;Shuaichen Guo ,&nbsp;Jiayi Tian ,&nbsp;Xi Xie ,&nbsp;Jie Shi ,&nbsp;Xing Zhang ,&nbsp;Chenchao Wang","doi":"10.1016/j.ajps.2025.101088","DOIUrl":"10.1016/j.ajps.2025.101088","url":null,"abstract":"<div><div>Wound healing is a series of complex biological events that are tightly coordinated by the body. However, this physiological process is compromised in a pathological setting and underlie conditions including diabetic complications, infectious diseases and chronic inflammatory conditions. Clinically, this translates to multiple pathological features collectively exhibited (microbial colonization, chronic inflammation and impaired regenerative processes). Due to these pathological features, modern wound care approaches have changed from simple passive coverage products to advanced dressing systems which incorporate multifunctional therapies. To comprehensively elucidate recent advancements in advanced wound dressings for drug delivery applications, this review systematically examines material-driven drug release strategies through multiple analytical dimensions. The discussion encompasses structurally engineered controlled-release systems featuring bilayer architectures, layer-by-layer assembly techniques and porous matrix designs, as well as intelligent stimulus-responsive mechanisms based on physicochemical properties, including physical condition modulation, swelling/degradation behavior control, dynamic chemical bond engineering and crosslinking network optimization. Through critical analysis of these cutting-edge technologies, this article provides insightful perspectives on their clinical translation potential and future trajectories.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 6","pages":"Article 101088"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691627","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 strategies and advances of mRNA translation booster mRNA翻译促进剂的策略与进展
IF 11.9 1区 医学
Asian Journal of Pharmaceutical Sciences Pub Date : 2025-12-01 Epub Date: 2025-09-02 DOI: 10.1016/j.ajps.2025.101090
Yingying Shi , Kedong Sun , Yilong Hu , Zeliang Lou , Yi Wang , Jian You
{"title":"The strategies and advances of mRNA translation booster","authors":"Yingying Shi ,&nbsp;Kedong Sun ,&nbsp;Yilong Hu ,&nbsp;Zeliang Lou ,&nbsp;Yi Wang ,&nbsp;Jian You","doi":"10.1016/j.ajps.2025.101090","DOIUrl":"10.1016/j.ajps.2025.101090","url":null,"abstract":"<div><div>The therapeutic efficacy and safety of mRNA-based drugs in immunological and nonimmunological applications are critically dependent on the translated protein yield, which requires precise modulation of mRNA expression kinetics. Among the factors influencing mRNA translation, immunogenicity and stability are pivotal in determining the longevity of protein production. Current optimization strategies have integrated (1) molecular engineering (<em>e.g.</em>, modified nucleotides), (2) advanced delivery systems (<em>e.g.</em>, lipid nanoparticles), and (3) adjuvant drug synergy. This review focuses on co-delivered adjuvant drugs and introduces the concept of \"mRNA translation boosters\" for the first time. mRNA translation boosters are classified as small-molecule compounds and macromolecular agents that improve translational fidelity through mechanisms including blockade of pattern recognition receptors, modulation of inflammatory cascades, facilitation of endosomal escape, and protection against enzymatic degradation. As clinically validated with COVID-19 mRNA vaccines, these boosters have now demonstrated expanded utility in gene editing therapies and protein replacement applications. This review addresses the immunological challenges encountered during mRNA transfection and translation while summarizing existing mRNA translation boosters that optimize protein expression kinetics. By establishing a mechanistic framework for booster selection and employment, this work provides translational guidance for advancing nucleic acid therapeutics towards their maximum clinical potential.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 6","pages":"Article 101090"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691628","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
A ROS/photo dual-responsive prodrug unimolecular micelle for boosted cancer immunotherapy 一种ROS/光双反应的前药单分子胶束用于增强癌症免疫治疗
IF 11.9 1区 医学
Asian Journal of Pharmaceutical Sciences Pub Date : 2025-12-01 Epub Date: 2025-11-16 DOI: 10.1016/j.ajps.2025.101104
Zeqian Huang , Congjun Xu , Yaqing Ding , Zishan Zeng , Huanxin Lin , Yong Luo , Xiaoyu Xu , Yanjuan Huang , Chunshun Zhao
{"title":"A ROS/photo dual-responsive prodrug unimolecular micelle for boosted cancer immunotherapy","authors":"Zeqian Huang ,&nbsp;Congjun Xu ,&nbsp;Yaqing Ding ,&nbsp;Zishan Zeng ,&nbsp;Huanxin Lin ,&nbsp;Yong Luo ,&nbsp;Xiaoyu Xu ,&nbsp;Yanjuan Huang ,&nbsp;Chunshun Zhao","doi":"10.1016/j.ajps.2025.101104","DOIUrl":"10.1016/j.ajps.2025.101104","url":null,"abstract":"<div><div>Integrating photodynamic therapy (PDT) with immunosuppression reversal represents a promising synergistic approach to boost cancer immunotherapy. However, the complicated components and cumbersome preparation procedures of the currently developed nano drug delivery systems heavily hinder their further clinical translation. Herein, a reactive oxygen species (ROS)/photo dual-responsive amphipathic prodrug (denoted as PPTN) was designed and synthesized by linking NLG919, an indoleamine-2,3-dioxygenase (IDO) inhibitor, with the photosensitizer protoporphyrin IX (PpIX) by a thioketal moiety, and further modifying with mPEG<sub>2k</sub>. PPTN could self-assemble into nanoscale unimolecular micelles in aqueous solution without additional excipients, increasing tumor accumulation while effectively addressing the pronounced hydrophobicity challenge of PpIX. Upon light exposure, PPTN generated ROS, not only directly damaging cancer cells, but also trigger the breakage of thioketal bond to accelerate simultaneous release of NLG919. Therefore, PPTN potentially act as a promising ROS/photo dual-responsive carrier-free prodrug delivery system for controllable drug release and specific tumor therapy. Moreover, PPTN induced simultaneous PDT-triggered immunogenic cell death (ICD) effect and specific IDO blockade to boost immune response, exhibiting potent suppression efficacy against primary and distant tumors. Overall, with the superiorities of easily controllable preparation procedures, synchronous drug delivery and ROS/photo dual-responsiveness, such a prodrug unimolecular micelle may represent a promising nanoplatform for photoactivated-immunotherapy.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 6","pages":"Article 101104"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691624","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
Development and preclinical evaluation of a novel FGFR3-targeted antibody-drug conjugate in bladder cancer 一种新型靶向fgfr3的膀胱癌抗体-药物偶联物的开发和临床前评估
IF 11.9 1区 医学
Asian Journal of Pharmaceutical Sciences Pub Date : 2025-12-01 Epub Date: 2025-10-13 DOI: 10.1016/j.ajps.2025.101095
Guangrui Fan , Xiongfei Luo , Kun Li , Ze Zhang , Chaohu Chen , Yibo Shi , Shu Cui , Yingru Wang , Dengtuo Wang , Zhijun Zhang , Zhilong Dong , Junqiang Tian , Liang Cheng , Juan Wang , Zhenxing Zhai , Yingqian Liu , Zhiping Wang
{"title":"Development and preclinical evaluation of a novel FGFR3-targeted antibody-drug conjugate in bladder cancer","authors":"Guangrui Fan ,&nbsp;Xiongfei Luo ,&nbsp;Kun Li ,&nbsp;Ze Zhang ,&nbsp;Chaohu Chen ,&nbsp;Yibo Shi ,&nbsp;Shu Cui ,&nbsp;Yingru Wang ,&nbsp;Dengtuo Wang ,&nbsp;Zhijun Zhang ,&nbsp;Zhilong Dong ,&nbsp;Junqiang Tian ,&nbsp;Liang Cheng ,&nbsp;Juan Wang ,&nbsp;Zhenxing Zhai ,&nbsp;Yingqian Liu ,&nbsp;Zhiping Wang","doi":"10.1016/j.ajps.2025.101095","DOIUrl":"10.1016/j.ajps.2025.101095","url":null,"abstract":"<div><div>Given the critical shortage of antibody-drug conjugates (ADCs) for bladder cancer (BCa), we developed a novel FGFR3-targeted ADC, LZU-WZLYFG001, composed of a humanized anti-FGFR3 IgG1 monoclonal antibody, a cleavable GGFG linker, and the payload DXD. The antibody was engineered in 293 cells and conjugated via thiol-based chemistry, achieving a drug-to-antibody ratio (DAR) of eight. Comprehensive preclinical assessments, including <em>in vitro</em> and <em>in vivo</em> studies using BCa cells, organoids, cell-derived xenograft and patient-derived xenograft (PDX) models, were conducted to evaluate efficacy, targeting ability, mechanism, safety and tissue distribution. LZU-WZLYFG001 demonstrated high purity, targeting specificity and low endotoxin levels, and it significantly inhibited BCa cell proliferation, migration and invasion at nanomolar concentrations, with efficacy strongly associated with FGFR3 expression levels. Mechanistic studies showed binding to FGFR3, internalization and lysosomal release of LZU-WZLYFG001. In organoid and xenograft models, LZU-WZLYFG001 exhibited superior efficacy compared with the gemcitabine + cisplatin (GC) regimen, particularly in GC-resistant PDX tumors, while also showing robust 3D penetration, a bystander effect, and no significant short-term toxicity. Collectively, these findings demonstrate that LZU-WZLYFG001 exhibits excellent preclinical efficacy and safety, and its superiority over GC, together with its activity in resistant tumors, highlights its potential as a novel therapeutic option for BCa.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 6","pages":"Article 101095"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622882","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
Critical Quality Attributes of Lipid Nanoparticles and In Vivo Fate 脂质纳米颗粒的关键质量属性和体内命运
IF 11.9 1区 医学
Asian Journal of Pharmaceutical Sciences Pub Date : 2025-12-01 Epub Date: 2025-09-01 DOI: 10.1016/j.ajps.2025.101092
Jiaxing Di , Yuhong Xu , Tonglei Li
{"title":"Critical Quality Attributes of Lipid Nanoparticles and In Vivo Fate","authors":"Jiaxing Di ,&nbsp;Yuhong Xu ,&nbsp;Tonglei Li","doi":"10.1016/j.ajps.2025.101092","DOIUrl":"10.1016/j.ajps.2025.101092","url":null,"abstract":"<div><div>Lipid nanoparticles (LNPs) have emerged as versatile carriers for the delivery of genetic medicines and small-molecule drugs, offering desired benefits for therapeutic applications. Optimization of the treatment efficacy of nanocarriers necessitates a thorough understanding of the connection between pharmacokinetics and physicochemical properties. This review consolidates scientific efforts to elucidate how LNP’s physicochemical attributes influence their <em>in vivo</em> fate, emphasizing particle size and shape, surface electric potential and ligand-binding chemistry. By examining the interplay between LNPs and biological barriers across various administration routes, this review provides insights into tailoring LNP properties for optimal delivery and reduced off-target effects. Recommendations for future research are provided to advance the study of LNP <em>in vivo</em> behaviors and offer a practical framework for optimizing <em>in vivo</em> performance through product design parameters.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 6","pages":"Article 101092"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594583","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
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