Journal of Controlled Release最新文献_第7页

Inhalable stealth liposomes improve peptide delivery for pulmonary fibrosis treatment 可吸入的隐形脂质体改善肺纤维化治疗的肽递送

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2026-01-22 DOI: 10.1016/j.jconrel.2026.114655

Ruibo Lin , Zhengqing Li , Yuelan Sun , Jianhao Shen , Xiang Cao , Yongfang Lin , Chang Fu , Yugen Zhu , Chaoqun Wang , Zheng Tan , Jiabin Zhang , Yongzhuo Huang , Shiyang Shen

Pulmonary fibrosis is a life-threatening lung disease with limited therapeutic options and suboptimal clinical outcomes. Peptide-based agents such as CSP7, a heptapeptide derived from caveolin-1, have shown promising antifibrotic activity with low systemic toxicity. However, effective inhaled administration of CSP7 is impeded by physiological barriers in fibrotic lungs, including alveolar edema fluid and clearance by inflammatory macrophages. Here, we report a high-loading stealth liposomal system designed to enhance pulmonary delivery of CSP7 by inhalation. CSP7 was covalently conjugated to an aliphatic lipid moiety to generate a lipidated prodrug (l-CSP7), enabling markedly improved incorporation into PEGylated stealth liposomes (l-CSP7/Lips) with about 4-fold higher encapsulation efficiency and drug loading. The optimized formulation also exhibited enhanced penetration through edematous alveolar fluid and reduced macrophage clearance. After deposition in the alveoli and uptake by myofibroblasts, intracellular enzymes cleave l-CSP7 to release active CSP7, thereby attenuating profibrotic cellular phenotypes. In bleomycin-induced idiopathic pulmonary fibrosis and silica-induced silicosis animal models, inhaled l-CSP7/Lips achieved superior alveolar delivery and therapeutic outcomes compared with free CSP7 and clinical drug nintedanib, reversing fibrotic remodeling, improving respiratory function, and reducing inflammation and collagen deposition. These results introduce a modular and translatable nanocarrier platform for inhalable peptide therapeutics and support a localized treatment strategy for pulmonary fibrosis and potentially other lung diseases.

肺纤维化是一种危及生命的肺部疾病，治疗选择有限，临床结果不理想。基于肽的药物，如CSP7，一种衍生自小窝蛋白-1的七肽，已经显示出有希望的抗纤维化活性和低全身毒性。然而，CSP7的有效吸入给药受到纤维化肺中的生理障碍的阻碍，包括肺泡水肿液和炎性巨噬细胞的清除。在这里，我们报告了一种高负荷隐形脂质体系统，旨在通过吸入增强CSP7的肺部递送。CSP7与脂肪脂共价偶联，生成脂化前药（l-CSP7），可显著改善与聚乙二醇化隐形脂质体（l-CSP7/Lips）的结合，包封效率和载药量提高约4倍。优化后的配方还表现出通过水肿肺泡液的渗透增强和巨噬细胞清除减少。在肺泡沉积并被肌成纤维细胞摄取后，细胞内酶裂解l-CSP7，释放活性CSP7，从而减弱促纤维化细胞表型。在博莱霉素诱导的特发性肺纤维化和二氧化硅诱导的矽肺动物模型中，与游离CSP7和临床药物尼达尼布相比，吸入l-CSP7/Lips获得了更好的肺泡输送和治疗效果，逆转了纤维化重塑，改善了呼吸功能，减少了炎症和胶原沉积。这些结果为可吸入肽治疗提供了一个模块化和可翻译的纳米载体平台，并支持肺纤维化和潜在的其他肺部疾病的局部治疗策略。

{"title":"Inhalable stealth liposomes improve peptide delivery for pulmonary fibrosis treatment","authors":"Ruibo Lin , Zhengqing Li , Yuelan Sun , Jianhao Shen , Xiang Cao , Yongfang Lin , Chang Fu , Yugen Zhu , Chaoqun Wang , Zheng Tan , Jiabin Zhang , Yongzhuo Huang , Shiyang Shen","doi":"10.1016/j.jconrel.2026.114655","DOIUrl":"10.1016/j.jconrel.2026.114655","url":null,"abstract":"<div><div>Pulmonary fibrosis is a life-threatening lung disease with limited therapeutic options and suboptimal clinical outcomes. Peptide-based agents such as CSP7, a heptapeptide derived from caveolin-1, have shown promising antifibrotic activity with low systemic toxicity. However, effective inhaled administration of CSP7 is impeded by physiological barriers in fibrotic lungs, including alveolar edema fluid and clearance by inflammatory macrophages. Here, we report a high-loading stealth liposomal system designed to enhance pulmonary delivery of CSP7 by inhalation. CSP7 was covalently conjugated to an aliphatic lipid moiety to generate a lipidated prodrug (l-CSP7), enabling markedly improved incorporation into PEGylated stealth liposomes (l-CSP7/Lips) with about 4-fold higher encapsulation efficiency and drug loading. The optimized formulation also exhibited enhanced penetration through edematous alveolar fluid and reduced macrophage clearance. After deposition in the alveoli and uptake by myofibroblasts, intracellular enzymes cleave l-CSP7 to release active CSP7, thereby attenuating profibrotic cellular phenotypes. In bleomycin-induced idiopathic pulmonary fibrosis and silica-induced silicosis animal models, inhaled l-CSP7/Lips achieved superior alveolar delivery and therapeutic outcomes compared with free CSP7 and clinical drug nintedanib, reversing fibrotic remodeling, improving respiratory function, and reducing inflammation and collagen deposition. These results introduce a modular and translatable nanocarrier platform for inhalable peptide therapeutics and support a localized treatment strategy for pulmonary fibrosis and potentially other lung diseases.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"391 ","pages":"Article 114655"},"PeriodicalIF":11.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021824","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

Self-assembled multicomponent prodrugs with GSH/ROS site-responsiveness enable spatiotemporally controlled release for treating resistant NSCLC 具有GSH/ROS位点响应性的自组装多组分前药可实现时空控制释放，用于治疗耐药NSCLC

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2026-01-22 DOI: 10.1016/j.jconrel.2026.114654

Chaozheng Zhang , Yao Chen , Xiaoke Shi , Yu Liu , Jingwei Zhou , Liang Leng , Tingting Zhang , Sijing Liu , Jin Liu , Tianbao Wang , Chuan Zheng , Chuantao Zhang , Yun Deng , Jinlin Guo , Jun Lu

The resistance of non-small cell lung cancer (NSCLC) to Paclitaxel (PTX) stems from the enhanced drug efflux mediated by ATP-binding cassette (ABC) transporters and the upregulated PARP1-dependent DNA repair pathway. To address this challenge, the present study constructed a self-assembled nanoprodrug, PSOTNs, featuring covalent conjugation of three therapeutic agents. Structurally, PTX was functionalized with a disulfide bond to confer GSH-responsive release, whereas Olaparib (OLP) was tethered via a thioketal linker for ROS-triggered liberation, and tetramethylpyrazine (TMP) was hydrophobically modified to drive self-assembly and facilitated mitochondria-specific targeting under acidic conditions. The delicate PSOTNs exhibited high drug loading, favorable colloidal stability, and enhanced tumor accumulation via the EPR effect. Upon cellular internalization, the elevated GSH level prompted rapid release of PTX, effectively inhibiting microtubule dynamics. Concurrently, TMP-mediated mitochondrial enrichment and the subsequent ROS-triggered cleavage released OLP along with cinnamaldehyde, which synergistically amplified oxidative stress, induced mitochondrial dysfunction, and suppressed P-glycoprotein-mediated drug efflux. In vitro assays demonstrated that PSOTNs significantly enhanced drug accumulation, induced DNA damage, provoked G2/M cell cycle arrest, and promoted apoptosis, outperforming both individual agents and the non-responsive control. Furthermore, PSOTNs revealed potent tumor growth inhibition in A549/Tax xenograft models, prolonged systemic circulation, and excellent biocompatibility. In summary, PSOTNs represent a novel nanotherapeutic strategy that overcomes PTX resistance through a triple synergistic mechanism of “microtubule disruption–DNA repair inhibition–mitochondrial function intervention,” offering a promising paradigm for the treatment of drug-resistant malignancies.

非小细胞肺癌（NSCLC）对紫杉醇（PTX）的耐药源于atp结合盒（ABC）转运体介导的药物外排增强和parp1依赖性DNA修复途径的上调。为了解决这一挑战，本研究构建了一种自组装的纳米前药PSOTNs，其特点是三种治疗剂的共价偶联。在结构上，PTX通过二硫键功能化以获得gsh响应释放，而奥拉帕尼（OLP）通过硫代连接物连接以获得ros触发的释放，而四甲基吡嗪（TMP）通过疏水修饰以驱动自组装并促进酸性条件下线粒体特异性靶向。精致的psotn表现出高药物负荷，良好的胶体稳定性，并通过EPR效应增强肿瘤积累。在细胞内化过程中，GSH水平升高促使PTX快速释放，有效抑制微管动力学。同时，tmp介导的线粒体富集和随后ros触发的裂解释放OLP和肉桂醛，协同放大氧化应激，诱导线粒体功能障碍，抑制p -糖蛋白介导的药物外排。体外实验表明，PSOTNs显著增强药物积累，诱导DNA损伤，引起G2/M细胞周期阻滞，促进细胞凋亡，优于单个药物和无反应对照。此外，PSOTNs在A549/Tax异种移植模型中显示出强大的肿瘤生长抑制作用，延长了体循环，并具有良好的生物相容性。总之，psotn代表了一种新的纳米治疗策略，通过“微管破坏- dna修复抑制-线粒体功能干预”三重协同机制克服PTX耐药性，为耐药恶性肿瘤的治疗提供了一个有希望的范例。

{"title":"Self-assembled multicomponent prodrugs with GSH/ROS site-responsiveness enable spatiotemporally controlled release for treating resistant NSCLC","authors":"Chaozheng Zhang , Yao Chen , Xiaoke Shi , Yu Liu , Jingwei Zhou , Liang Leng , Tingting Zhang , Sijing Liu , Jin Liu , Tianbao Wang , Chuan Zheng , Chuantao Zhang , Yun Deng , Jinlin Guo , Jun Lu","doi":"10.1016/j.jconrel.2026.114654","DOIUrl":"10.1016/j.jconrel.2026.114654","url":null,"abstract":"<div><div>The resistance of non-small cell lung cancer (NSCLC) to Paclitaxel (PTX) stems from the enhanced drug efflux mediated by ATP-binding cassette (ABC) transporters and the upregulated PARP1-dependent DNA repair pathway. To address this challenge, the present study constructed a self-assembled nanoprodrug, PSOTNs, featuring covalent conjugation of three therapeutic agents. Structurally, PTX was functionalized with a disulfide bond to confer GSH-responsive release, whereas Olaparib (OLP) was tethered via a thioketal linker for ROS-triggered liberation, and tetramethylpyrazine (TMP) was hydrophobically modified to drive self-assembly and facilitated mitochondria-specific targeting under acidic conditions. The delicate PSOTNs exhibited high drug loading, favorable colloidal stability, and enhanced tumor accumulation via the EPR effect. Upon cellular internalization, the elevated GSH level prompted rapid release of PTX, effectively inhibiting microtubule dynamics. Concurrently, TMP-mediated mitochondrial enrichment and the subsequent ROS-triggered cleavage released OLP along with cinnamaldehyde, which synergistically amplified oxidative stress, induced mitochondrial dysfunction, and suppressed P-glycoprotein-mediated drug efflux. In vitro assays demonstrated that PSOTNs significantly enhanced drug accumulation, induced DNA damage, provoked G2/M cell cycle arrest, and promoted apoptosis, outperforming both individual agents and the non-responsive control. Furthermore, PSOTNs revealed potent tumor growth inhibition in A549/Tax xenograft models, prolonged systemic circulation, and excellent biocompatibility. In summary, PSOTNs represent a novel nanotherapeutic strategy that overcomes PTX resistance through a triple synergistic mechanism of “microtubule disruption–DNA repair inhibition–mitochondrial function intervention,” offering a promising paradigm for the treatment of drug-resistant malignancies.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"391 ","pages":"Article 114654"},"PeriodicalIF":11.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032812","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

Corrigendum to “Escherichia coli Nissle 1917 outer membrane vesicles encapsulating oncolytic virus remodel tumor-associated macrophages and kill prostate cancer cells” [Journal of Controlled Release Volume 390, 10 February 2026, 114514/ COREL-D-25-06760] “Escherichia coli Nissle 1917外膜囊泡包裹溶瘤病毒重塑肿瘤相关巨噬细胞并杀死前列腺癌细胞”的勘误表[Journal of control Release Volume 390, 2026年2月10日，114514/ corell - d -25-06760]

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2026-01-21 DOI: 10.1016/j.jconrel.2026.114633

Jian-Xuan Sun , Si-Yang Ma , Jing-Yu Xu , Maimaiti Abudureyimu , Ye An , Jin-Zhou Xu , Si-Han Zhang , Zi-Yi Zhang , Ci-Xiang Guo , Bin-Lei Liu , Shao-Gang Wang , Qi-Dong Xia

引用次数: 0

Probiotic biofilms: A novel encapsulation system for bioactive modalities 益生菌生物膜：一种具有生物活性的新型封装系统

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2026-01-21 DOI: 10.1016/j.jconrel.2026.114651

Haifu Jia , Jinghang Zhang , Yuanyuan Li , Bo Qu , Feng Zhao , Qianyu Zhao , Yujun Jiang

Bioactive modalities have garnered extensive research interest due to their potential in promoting human health. However, maintaining their biological activity during processing, storage, and digestion remains a significant challenge. Encapsulation has been recognized as an effective strategy to enhance the stability of these compounds. Conventional encapsulation techniques, however, often suffer from limited protective efficacy and inadequate intestinal adhesion. While biofilm-based encapsulation of probiotics provides a natural protective barrier for these microorganisms, its application has recently expanded beyond probiotics to include a wider range of bioactive modalities. Compared to traditional methods, probiotic biofilm-based encapsulation systems have emerged as a promising platform for the delivery of various bioactive modalities, owing to their superior stability, strong mucoadhesive properties, and excellent biocompatibility. This review outlines the types of bacterial biofilms and their beneficial functions, and discusses the advantages of probiotic biofilm-mediated encapsulation systems. It also comprehensively describes the composition and classification of biofilm encapsulation systems, and critically evaluates the strengths and limitations of different types of biofilm-based carriers. Furthermore, we summarize the applications of biofilm encapsulation systems in the fields of human health and food technology. Finally, we address the current key challenges facing the use of biofilm encapsulation for bioactive modalities and suggest potential.

生物活性模式因其促进人类健康的潜力而获得了广泛的研究兴趣。然而，在加工、储存和消化过程中保持其生物活性仍然是一个重大挑战。包封已被认为是提高这些化合物稳定性的有效策略。然而，传统的包封技术往往受到保护效果有限和肠道粘连不足的影响。虽然基于生物膜的益生菌包封为这些微生物提供了天然的保护屏障，但其应用最近已扩展到益生菌之外，包括更广泛的生物活性形式。与传统方法相比，基于益生菌生物膜的胶囊化系统由于其优越的稳定性、强黏附性能和优异的生物相容性，已成为一种有前景的平台，用于输送各种生物活性模式。本文综述了细菌生物膜的类型及其有益功能，并讨论了益生菌生物膜介导的包封系统的优点。它还全面描述了生物膜封装系统的组成和分类，并批判性地评估了不同类型的基于生物膜的载体的优势和局限性。综述了生物膜封装系统在人体健康和食品技术领域的应用。最后，我们解决了当前生物膜封装在生物活性模式中所面临的主要挑战，并提出了潜力。

{"title":"Probiotic biofilms: A novel encapsulation system for bioactive modalities","authors":"Haifu Jia , Jinghang Zhang , Yuanyuan Li , Bo Qu , Feng Zhao , Qianyu Zhao , Yujun Jiang","doi":"10.1016/j.jconrel.2026.114651","DOIUrl":"10.1016/j.jconrel.2026.114651","url":null,"abstract":"<div><div>Bioactive modalities have garnered extensive research interest due to their potential in promoting human health. However, maintaining their biological activity during processing, storage, and digestion remains a significant challenge. Encapsulation has been recognized as an effective strategy to enhance the stability of these compounds. Conventional encapsulation techniques, however, often suffer from limited protective efficacy and inadequate intestinal adhesion. While biofilm-based encapsulation of probiotics provides a natural protective barrier for these microorganisms, its application has recently expanded beyond probiotics to include a wider range of bioactive modalities. Compared to traditional methods, probiotic biofilm-based encapsulation systems have emerged as a promising platform for the delivery of various bioactive modalities, owing to their superior stability, strong mucoadhesive properties, and excellent biocompatibility. This review outlines the types of bacterial biofilms and their beneficial functions, and discusses the advantages of probiotic biofilm-mediated encapsulation systems. It also comprehensively describes the composition and classification of biofilm encapsulation systems, and critically evaluates the strengths and limitations of different types of biofilm-based carriers. Furthermore, we summarize the applications of biofilm encapsulation systems in the fields of human health and food technology. Finally, we address the current key challenges facing the use of biofilm encapsulation for bioactive modalities and suggest potential.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"391 ","pages":"Article 114651"},"PeriodicalIF":11.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014290","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

Sequentially responsive nanogels enhance probiotic delivery and reprogram M2 macrophage polarization for synergistic alleviation of colitis 顺序反应纳米凝胶增强益生菌输送和重编程M2巨噬细胞极化，协同缓解结肠炎

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2026-01-20 DOI: 10.1016/j.jconrel.2026.114652

Weigang Zhong , Lei Xu , Xuehui Zhang , Xuming Deng , Xue Shen

The interplay of multiple pathologic features in inflammatory bowel disease (IBD) persistently disrupts M2 macrophage-mediated intestinal wound repair. Although probiotic therapy represents a sustainable treatment strategy for IBD, it is still limited by inefficient oral delivery and inability to simultaneously address multiple pathologic features. Accordingly, a multifunctional integrated nanogels (Se-MHA/BG NGs) with both sequential response and diverse bioactivities were designed for coating the model probiotic Escherichia coli Nissle 1917 (EcN@Se-MHA/BG) in this study. During digestion, EcN@Se-MHA/BG formed insoluble complexes to protect EcN against acidic pH conditions, while the diselenide-crosslinked NGs coating degraded rapidly in response to the high levels of reactive oxygen species (ROS) characteristic of inflammatory microenvironments, thereby improving the colonization efficiency of EcN by 560%. Moreover, the degraded NGs, functionalized with mannose moieties, promoted the uptake efficiency of M2 macrophages and inhibited their repolarization by alleviating IBD-related symptoms of epithelial barrier damage, cellular oxidative stress and inflammation. Based on these functions, EcN@Se-MHA/BG exerted both therapeutic and prophylactic effects to improve colonic pathological symptoms and positively regulate gut microbiota in a DSS-induced murine colitis model. Overall, Se-MHA/BG NGs demonstrated promising potential as a versatile coating system to enhance the clinical therapeutic performance of probiotic-based therapies for IBD.

炎症性肠病（IBD）中多种病理特征的相互作用持续破坏M2巨噬细胞介导的肠伤口修复。虽然益生菌治疗是IBD的一种可持续的治疗策略，但它仍然受到口服给药效率低下和无法同时解决多种病理特征的限制。因此，本研究设计了一种具有顺序反应和多种生物活性的多功能集成纳米凝胶（Se-MHA/BG ng），用于模型益生菌大肠杆菌尼索尔1917 （EcN@Se-MHA/BG）的包被。在消化过程中，EcN@Se-MHA/BG形成不溶性配合物，保护EcN免受酸性pH条件的影响，而二硒交联的NGs涂层在炎症微环境的高水平活性氧（ROS）特征下迅速降解，从而将EcN的定殖效率提高了560%。此外，被甘露糖功能化的降解的NGs通过减轻ibd相关的上皮屏障损伤、细胞氧化应激和炎症症状，提高了M2巨噬细胞的摄取效率，抑制了M2巨噬细胞的复极化。基于这些功能，EcN@Se-MHA/BG在dss诱导的小鼠结肠炎模型中具有改善结肠病理症状和正向调节肠道微生物群的治疗和预防作用。总的来说，Se-MHA/BG ng作为一种多功能涂层系统，在增强益生菌治疗IBD的临床治疗性能方面表现出了很大的潜力。

{"title":"Sequentially responsive nanogels enhance probiotic delivery and reprogram M2 macrophage polarization for synergistic alleviation of colitis","authors":"Weigang Zhong , Lei Xu , Xuehui Zhang , Xuming Deng , Xue Shen","doi":"10.1016/j.jconrel.2026.114652","DOIUrl":"10.1016/j.jconrel.2026.114652","url":null,"abstract":"<div><div>The interplay of multiple pathologic features in inflammatory bowel disease (IBD) persistently disrupts M2 macrophage-mediated intestinal wound repair. Although probiotic therapy represents a sustainable treatment strategy for IBD, it is still limited by inefficient oral delivery and inability to simultaneously address multiple pathologic features. Accordingly, a multifunctional integrated nanogels (Se-MHA/BG NGs) with both sequential response and diverse bioactivities were designed for coating the model probiotic <em>Escherichia coli Nissle 1917</em> (EcN@Se-MHA/BG) in this study. During digestion, EcN@Se-MHA/BG formed insoluble complexes to protect EcN against acidic pH conditions, while the diselenide-crosslinked NGs coating degraded rapidly in response to the high levels of reactive oxygen species (ROS) characteristic of inflammatory microenvironments, thereby improving the colonization efficiency of EcN by 560%. Moreover, the degraded NGs, functionalized with mannose moieties, promoted the uptake efficiency of M2 macrophages and inhibited their repolarization by alleviating IBD-related symptoms of epithelial barrier damage, cellular oxidative stress and inflammation. Based on these functions, EcN@Se-MHA/BG exerted both therapeutic and prophylactic effects to improve colonic pathological symptoms and positively regulate gut microbiota in a DSS-induced murine colitis model. Overall, Se-MHA/BG NGs demonstrated promising potential as a versatile coating system to enhance the clinical therapeutic performance of probiotic-based therapies for IBD.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"391 ","pages":"Article 114652"},"PeriodicalIF":11.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014327","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

Bioinspired nanomicelles with octopus-like adhesion for microenvironmental reprogramming in periodontitis 具有章鱼样黏附的仿生纳米胶束用于牙周炎的微环境重编程

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2026-01-20 DOI: 10.1016/j.jconrel.2026.114649

Yingke Liu , Jiaxin Li , Rong Guo , Zhipeng Tian , Yang Wang , Man Li , Guanyin Zhu , Zhihe Zhao

Periodontitis is a multifactorial disease characterized by bacterial infection, inflammation, oxidative stress, and dysregulated bone remodeling, for which current treatments remain limited. Effective treatment requires not only antimicrobial action but also coordinated modulation of immune and regenerative pathways within the periodontal microenvironment. Here, this study reports a bioinspired “octopus-like” nanomicelle platform with mucoadhesive tentacles and immune-targeting surfaces, designed to enhance drug retention, selective delivery, and multifunctional therapeutic performance. Phenylboronic acid modification enables high-affinity binding to sialic acids in mucosal glycoproteins, prolonging local retention, while fucoidan decoration directs nanomicelles to scavenger receptors on macrophages and neutrophils, the key effector cells in periodontitis. As cannabidiol was used as a potential therapeutic payload, the nanomicelles exhibited potent antibacterial activity against Staphylococcus aureus and Porphyromonas gingivalis, immune microenvironment remodeling and enhanced osteogenic differentiation in vivo. This dual-targeting strategy suppresses macrophage inflammation and oxidative stress via modulating Toll-like receptor, janus kinase-signal transducer and activator of transcription (JAK–STAT), and advanced glycation end products-Receptor for AGEs (AGE–RAGE) pathways, while also reducing neutrophil extracellular traps formation via regulation of apoptosis, mitochondrial depolarization, and calcium signaling. In a mouse periodontitis model, the platform achieved superior therapeutic outcomes compared to free drug. Together, this multifunctional adhesive nanoplatform integrates mucoadhesion, immune modulation, antimicrobial activity, and bone regeneration, offering a versatile and generalizable strategy for periodontitis therapy and broader microenvironmental reprogramming in chronic inflammatory diseases.

牙周炎是一种多因素疾病，以细菌感染、炎症、氧化应激和骨重塑失调为特征，目前的治疗方法仍然有限。有效的治疗不仅需要抗菌作用，还需要在牙周微环境中协调调节免疫和再生途径。在这里，本研究报告了一种具有黏附触须和免疫靶向表面的生物启发的“章鱼状”纳米胶束平台，旨在增强药物保留，选择性递送和多功能治疗性能。苯基硼酸修饰可以与粘膜糖蛋白中的唾液酸高亲和力结合，延长局部滞留时间，而岩藻聚糖修饰可以引导纳米胶束到达巨噬细胞和中性粒细胞（牙周炎的关键效应细胞）上的清道夫受体。由于大麻二酚被用作潜在的治疗有效载荷，纳米胶束在体内表现出对金黄色葡萄球菌和牙龈卟啉单胞菌的有效抗菌活性，免疫微环境重塑和增强成骨分化。这种双靶向策略通过调节toll样受体、janus激酶信号转导和转录激活因子（JAK-STAT）和晚期糖基化终产物- AGEs受体（AGE-RAGE）途径抑制巨噬细胞炎症和氧化应激，同时通过调节凋亡、线粒体去极化和钙信号传导减少中性粒细胞胞外陷阱的形成。在小鼠牙周炎模型中，与游离药物相比，该平台取得了更好的治疗效果。总之，这种多功能黏附纳米平台集成了黏附、免疫调节、抗菌活性和骨再生，为牙周炎治疗和慢性炎症疾病的微环境重编程提供了一种通用的策略。

{"title":"Bioinspired nanomicelles with octopus-like adhesion for microenvironmental reprogramming in periodontitis","authors":"Yingke Liu , Jiaxin Li , Rong Guo , Zhipeng Tian , Yang Wang , Man Li , Guanyin Zhu , Zhihe Zhao","doi":"10.1016/j.jconrel.2026.114649","DOIUrl":"10.1016/j.jconrel.2026.114649","url":null,"abstract":"<div><div>Periodontitis is a multifactorial disease characterized by bacterial infection, inflammation, oxidative stress, and dysregulated bone remodeling, for which current treatments remain limited. Effective treatment requires not only antimicrobial action but also coordinated modulation of immune and regenerative pathways within the periodontal microenvironment. Here, this study reports a bioinspired “octopus-like” nanomicelle platform with mucoadhesive tentacles and immune-targeting surfaces, designed to enhance drug retention, selective delivery, and multifunctional therapeutic performance. Phenylboronic acid modification enables high-affinity binding to sialic acids in mucosal glycoproteins, prolonging local retention, while fucoidan decoration directs nanomicelles to scavenger receptors on macrophages and neutrophils, the key effector cells in periodontitis. As cannabidiol was used as a potential therapeutic payload, the nanomicelles exhibited potent antibacterial activity against <em>Staphylococcus aureus</em> and <em>Porphyromonas gingivalis</em>, immune microenvironment remodeling and enhanced osteogenic differentiation <em>in vivo</em>. This dual-targeting strategy suppresses macrophage inflammation and oxidative stress <em>via</em> modulating Toll-like receptor, janus kinase-signal transducer and activator of transcription (JAK–STAT), and advanced glycation end products-Receptor for AGEs (AGE–RAGE) pathways, while also reducing neutrophil extracellular traps formation <em>via</em> regulation of apoptosis, mitochondrial depolarization, and calcium signaling. In a mouse periodontitis model, the platform achieved superior therapeutic outcomes compared to free drug. Together, this multifunctional adhesive nanoplatform integrates mucoadhesion, immune modulation, antimicrobial activity, and bone regeneration, offering a versatile and generalizable strategy for periodontitis therapy and broader microenvironmental reprogramming in chronic inflammatory diseases.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114649"},"PeriodicalIF":11.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014302","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

Next generation CAR-T cells to tackle solid tumors 下一代CAR-T细胞治疗实体瘤

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2026-01-20 DOI: 10.1016/j.jconrel.2026.114650

Teresa Abreu , Ana Godinho-Santos , Ana Teresa Amaral , Artur Paiva , João Nuno Moreira , Joao Goncalves

The genetic modification of human T cells to express chimeric antigen receptors (CAR-T cells) has revolutionized cancer immunotherapy by redirecting their cytotoxicity towards specific tumor antigens. While CAR-T cell therapies have demonstrated remarkable success in hematological malignancies, their translation to solid tumors remains limited by several challenges. These include the lack of exclusive tumor antigens and intrinsic tumor heterogeneity, which contribute to suboptimal targeting and increase the risk of on-target, off-tumor effects. Additionally, solid tumors present a complex and hostile tumor microenvironment (TME), characterized by multiple physical barriers and immunosuppressive mechanisms that severely hinder CAR-T cells trafficking, persistence, and anti-tumor activity. A deeper understanding of these obstacles has fueled the development of next-generation CAR designs equipped with advanced synthetic biology approaches. Improved antigen specificity with logic-gated systems, multiple-input CAR designs, co-expression of cytokine receptors, armored CARs, and engineered resistance to immunosuppressive cues in the form of chimeric switch or dominant negative receptors have emerged in response. In this context, this review provides a stepwise and comparative overview of the major biological and structural challenges limiting CAR T-cells efficacy in solid tumors. It critically discusses the innovative CAR constructs developed to overcome each of these obstacles – from antigen selection to trafficking and TME remodeling - offering a forward-looking framework to guide future research and accelerate the translation of CAR-T therapies beyond blood cancers.

通过对人类T细胞进行基因修饰以表达嵌合抗原受体（CAR-T细胞），将其细胞毒性转向特定的肿瘤抗原，从而彻底改变了癌症免疫治疗。虽然CAR-T细胞疗法在血液系统恶性肿瘤中取得了显著的成功，但它们向实体肿瘤的转化仍然受到一些挑战的限制。这些因素包括缺乏特异性的肿瘤抗原和固有的肿瘤异质性，这些因素会导致非最佳靶向，并增加靶向、非肿瘤效应的风险。此外，实体肿瘤呈现出复杂和敌对的肿瘤微环境（TME），以多种物理屏障和免疫抑制机制为特征，严重阻碍CAR-T细胞的运输、持久性和抗肿瘤活性。对这些障碍的深入了解推动了下一代CAR设计的发展，这些设计配备了先进的合成生物学方法。通过逻辑门控系统、多输入CAR设计、细胞因子受体的共表达、装甲CAR以及嵌合开关或显性阴性受体形式的免疫抑制信号的工程化抗性，抗原特异性得到了改善。在此背景下，本综述提供了限制CAR - t细胞在实体瘤中疗效的主要生物学和结构挑战的逐步和比较概述。它批判性地讨论了为克服这些障碍而开发的创新CAR结构-从抗原选择到运输和TME重塑-提供了一个前瞻性的框架，以指导未来的研究并加速CAR- t疗法超越血癌的转化。

{"title":"Next generation CAR-T cells to tackle solid tumors","authors":"Teresa Abreu , Ana Godinho-Santos , Ana Teresa Amaral , Artur Paiva , João Nuno Moreira , Joao Goncalves","doi":"10.1016/j.jconrel.2026.114650","DOIUrl":"10.1016/j.jconrel.2026.114650","url":null,"abstract":"<div><div>The genetic modification of human T cells to express chimeric antigen receptors (CAR-T cells) has revolutionized cancer immunotherapy by redirecting their cytotoxicity towards specific tumor antigens. While CAR-T cell therapies have demonstrated remarkable success in hematological malignancies, their translation to solid tumors remains limited by several challenges. These include the lack of exclusive tumor antigens and intrinsic tumor heterogeneity, which contribute to suboptimal targeting and increase the risk of on-target, off-tumor effects. Additionally, solid tumors present a complex and hostile tumor microenvironment (TME), characterized by multiple physical barriers and immunosuppressive mechanisms that severely hinder CAR-T cells trafficking, persistence, and anti-tumor activity. A deeper understanding of these obstacles has fueled the development of next-generation CAR designs equipped with advanced synthetic biology approaches. Improved antigen specificity with logic-gated systems, multiple-input CAR designs, co-expression of cytokine receptors, armored CARs, and engineered resistance to immunosuppressive cues in the form of chimeric switch or dominant negative receptors have emerged in response. In this context, this review provides a stepwise and comparative overview of the major biological and structural challenges limiting CAR T-cells efficacy in solid tumors. It critically discusses the innovative CAR constructs developed to overcome each of these obstacles – from antigen selection to trafficking and TME remodeling - offering a forward-looking framework to guide future research and accelerate the translation of CAR-T therapies beyond blood cancers.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"391 ","pages":"Article 114650"},"PeriodicalIF":11.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014297","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

Perfluorohexane/hemoglobin nano-oxygen carriers enhance transplanted islet graft survival via hypoxia alleviation and mitochondrial repair 全氟己烷/血红蛋白纳米氧载体通过缺氧缓解和线粒体修复提高移植胰岛移植物存活

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2026-01-19 DOI: 10.1016/j.jconrel.2026.114646

Di Huang , Ying Zhang , Zhuoxun Huang , Xiaoyue Chen , Yifei Yang , Yang Cheng , Yifan Qiu , Yixuan Zhu , Jie Dong , Haoxiong Guan , Yannan Shi , Qing Yao

Islet cell transplantation offers a promising therapeutic approach for type 1 diabetes by restoring endogenous, real-time blood glucose regulation. Despite its clinical potential, widespread application remains limited due to critical challenges such as donor scarcity, the need for lifelong immunosuppression, and significant graft loss caused by immediate blood-mediated inflammatory responses and ischemia/hypoxia at the transplantation site. To address these issues, we developed a novel nano‑oxygen delivery platform based on perfluorohexane/hemoglobin nanoparticles (PFH/Hb NPs). In this system, PFH enhances oxygen-carrying capacity while hemoglobin improves the biocompatibility of the perfluorinated core, enabling effective oxygen delivery within the hypoxic microenvironment. The PFH/Hb NPs synergistically alleviated oxidative stress and inflammatory responses, promoted early-stage neovascularization, and restored mitochondrial homeostasis by regulating fusion-fission dynamics. These effects collectively improved the survival and function of transplanted islets in vivo. This study provides a translationally relevant strategy to optimize graft microenvironments, offering new prospects for safer and more efficient minimally invasive islet transplantation to potentially cure diabetes.

胰岛细胞移植通过恢复内源性的实时血糖调节，为1型糖尿病提供了一种很有前途的治疗方法。尽管其具有临床潜力，但由于供体稀缺、需要终身免疫抑制、移植部位立即血液介导的炎症反应和缺血/缺氧引起的严重移植物损失等关键挑战，其广泛应用仍然受到限制。为了解决这些问题，我们开发了一种基于全氟己烷/血红蛋白纳米颗粒（PFH/Hb NPs）的新型纳米氧气输送平台。在该系统中，PFH增强了携氧能力，而血红蛋白提高了全氟核心的生物相容性，从而在缺氧微环境中实现了有效的氧气输送。PFH/Hb NPs协同缓解氧化应激和炎症反应，促进早期新生血管形成，并通过调节融合-裂变动力学恢复线粒体稳态。这些作用共同提高了移植胰岛的存活和体内功能。本研究提供了一种翻译相关的策略来优化移植微环境，为更安全、更有效的微创胰岛移植治疗糖尿病提供了新的前景。

{"title":"Perfluorohexane/hemoglobin nano-oxygen carriers enhance transplanted islet graft survival via hypoxia alleviation and mitochondrial repair","authors":"Di Huang , Ying Zhang , Zhuoxun Huang , Xiaoyue Chen , Yifei Yang , Yang Cheng , Yifan Qiu , Yixuan Zhu , Jie Dong , Haoxiong Guan , Yannan Shi , Qing Yao","doi":"10.1016/j.jconrel.2026.114646","DOIUrl":"10.1016/j.jconrel.2026.114646","url":null,"abstract":"<div><div>Islet cell transplantation offers a promising therapeutic approach for type 1 diabetes by restoring endogenous, real-time blood glucose regulation. Despite its clinical potential, widespread application remains limited due to critical challenges such as donor scarcity, the need for lifelong immunosuppression, and significant graft loss caused by immediate blood-mediated inflammatory responses and ischemia/hypoxia at the transplantation site. To address these issues, we developed a novel nano‑oxygen delivery platform based on perfluorohexane/hemoglobin nanoparticles (PFH/Hb NPs). In this system, PFH enhances oxygen-carrying capacity while hemoglobin improves the biocompatibility of the perfluorinated core, enabling effective oxygen delivery within the hypoxic microenvironment. The PFH/Hb NPs synergistically alleviated oxidative stress and inflammatory responses, promoted early-stage neovascularization, and restored mitochondrial homeostasis by regulating fusion-fission dynamics. These effects collectively improved the survival and function of transplanted islets in vivo. This study provides a translationally relevant strategy to optimize graft microenvironments, offering new prospects for safer and more efficient minimally invasive islet transplantation to potentially cure diabetes.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"391 ","pages":"Article 114646"},"PeriodicalIF":11.5,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000574","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

Corrigendum to ‘An injectable thermoresponsive-hydrogel for lamellar keratoplasty: In-situ releases celastrol and hampers corneal scars [Journal of Controlled Release 369 (2024) 604–616] 一种用于板层角膜移植术的可注射热反应水凝胶的勘误：原位释放celastrol和阻碍角膜疤痕[Journal of control Release 369 (2024) 604-616]

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2026-01-19 DOI: 10.1016/j.jconrel.2026.114616

Zhanrong Li , Ruixing Liu , Xiacong Zhang , Zhihua Guo , Xingchen Geng , Dandan Chu , Haohao Cui , Afang Zhang , Wen Li , Lei Zhu , Jingguo Li

引用次数: 0

Dual-biomimetic Nanodecoys reprogram cardiac macrophages by suppressing STING signaling for heart repair 双仿生纳米诱饵通过抑制心脏修复的STING信号重编程心脏巨噬细胞

IF 11.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release

Pub Date : 2026-01-19 DOI: 10.1016/j.jconrel.2026.114647

Peng Wang , Ruobing Li , Jinjin Ni , Duanbin Li , Mei Hua Ting , Kai Ma , Guosheng Fu , Junbo Ge , Shenggang Zhao , Wenbin Zhang , Ning Zhang , Xianglan Liu

Myocardial infarction (MI) initiates sterile inflammation through the release of cytosolic DNA from necrotic cardiomyocytes, which aberrantly activates the cGAS-STING pathway in infiltrating macrophages and drives their polarization toward a pro-inflammatory M1 phenotype. Although the immunosuppressive oligodeoxynucleotide A151 can antagonize cGAS activation, its therapeutic utility is limited by enzymatic instability and inefficient cellular delivery. Here, we report a dual-biomimetic nanodecoy (A151@APPL) that integrates platelet membrane vesicles for infarct-specific targeting with arginine-modified phosphatidylserine lipids to promote macrophage uptake and enable nitric oxide-driven propulsion in redox-enriched tissue. This construct achieves efficient cytosolic delivery of A151 to lesional macrophages, suppressing the cGAS-STING axis, reducing pro-inflammatory cytokine expression, and reprogramming macrophages toward a reparative M2-like state. In a murine MI model, A151@APPL treatment attenuated ventricular inflammation, limited fibrotic remodeling, and restored cardiac performance. These findings establish a context-responsive delivery strategy that selectively modulates innate immune signaling and promotes cardiac repair following ischemic injury.

心肌梗死（MI）通过坏死心肌细胞释放胞质DNA引发无菌炎症，从而异常激活浸润性巨噬细胞中的cGAS-STING通路，并推动其向促炎M1表型极化。尽管免疫抑制寡脱氧核苷酸A151可以拮抗cGAS激活，但其治疗效用受到酶的不稳定性和细胞递送效率低下的限制。在这里，我们报道了一种双仿生纳米诱饵（A151@APPL），它将用于梗死特异性靶向的血小板膜泡与精氨酸修饰的磷脂酰丝氨酸脂结合起来，促进巨噬细胞摄取，并在氧化还原富集的组织中实现一氧化氮驱动的推进。该结构实现了A151向病变巨噬细胞的有效胞质递送，抑制cGAS-STING轴，减少促炎细胞因子表达，并将巨噬细胞重编程为修复性m2样状态。在小鼠心肌梗死模型中，A151@APPL治疗减轻了心室炎症，限制了纤维化重塑，恢复了心脏功能。这些发现建立了一种情境响应递送策略，选择性地调节先天免疫信号并促进缺血性损伤后的心脏修复。

{"title":"Dual-biomimetic Nanodecoys reprogram cardiac macrophages by suppressing STING signaling for heart repair","authors":"Peng Wang , Ruobing Li , Jinjin Ni , Duanbin Li , Mei Hua Ting , Kai Ma , Guosheng Fu , Junbo Ge , Shenggang Zhao , Wenbin Zhang , Ning Zhang , Xianglan Liu","doi":"10.1016/j.jconrel.2026.114647","DOIUrl":"10.1016/j.jconrel.2026.114647","url":null,"abstract":"<div><div>Myocardial infarction (MI) initiates sterile inflammation through the release of cytosolic DNA from necrotic cardiomyocytes, which aberrantly activates the cGAS-STING pathway in infiltrating macrophages and drives their polarization toward a pro-inflammatory M1 phenotype. Although the immunosuppressive oligodeoxynucleotide A151 can antagonize cGAS activation, its therapeutic utility is limited by enzymatic instability and inefficient cellular delivery. Here, we report a dual-biomimetic nanodecoy (A151@APPL) that integrates platelet membrane vesicles for infarct-specific targeting with arginine-modified phosphatidylserine lipids to promote macrophage uptake and enable nitric oxide-driven propulsion in redox-enriched tissue. This construct achieves efficient cytosolic delivery of A151 to lesional macrophages, suppressing the cGAS-STING axis, reducing pro-inflammatory cytokine expression, and reprogramming macrophages toward a reparative M2-like state. In a murine MI model, A151@APPL treatment attenuated ventricular inflammation, limited fibrotic remodeling, and restored cardiac performance. These findings establish a context-responsive delivery strategy that selectively modulates innate immune signaling and promotes cardiac repair following ischemic injury.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"391 ","pages":"Article 114647"},"PeriodicalIF":11.5,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000572","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