Journal of Controlled Release最新文献_第7页

Progress towards a prodrug/enzyme intranasal delivery system for rapid prevention/reversal of seizure emergency 用于快速预防/逆转癫痫紧急情况的前药/酶鼻内给药的进展

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-20 DOI: 10.1016/j.jconrel.2025.114250

Ronald A. Siegel , Davin Rautiola , Narsihmulu Cheryala , Gunda I. Georg , James C. Cloyd

{"title":"Progress towards a prodrug/enzyme intranasal delivery system for rapid prevention/reversal of seizure emergency","authors":"Ronald A. Siegel , Davin Rautiola , Narsihmulu Cheryala , Gunda I. Georg , James C. Cloyd","doi":"10.1016/j.jconrel.2025.114250","DOIUrl":"10.1016/j.jconrel.2025.114250","url":null,"abstract":"<div><div>Sporadic epileptic seizure emergencies (SEs) require rapid treatment to prevent the emergence of status epilepticus, a condition that can present morbidities and possible mortality. First-line treatment of SEs has involved IV administration of benzodiazepines (BZDs) to the patient in the emergency department of a hospital, outpatient buccal administration, or administration of an outpatient rectal gel. These therapies are suboptimal for a variety of reasons, and recently, BZD nasal sprays have been introduced. Such sprays must solve the problem of poor aqueous solubility of BZDs. The present sprays contain organic excipients, which can be irritating, and the BZDs show either moderate bioavailability or slow absorption. In this Perspective we review work on a purely aqueous formulation containing avizafone (AVF), a prodrug of the BZD diazepam (DZP), and the converting enzyme <em>human amino peptidase B</em> (APB). Mixing these two ingredients at the point of administration creates a supersaturated aqueous DZP solution, which is rapidly absorbed across the nasal mucosa without the irritation mentioned above. We review characterization of the enzyme reaction and <em>in vivo</em> studies in which Sprague-Dawley rats were administered the AVF/APB formulation intranasally. Tmax values of DZP in both plasma and brain were both about 8 min, and brain concentrations appear to have reached 70 ng/g, which is considered adequate for controlling seizures within 2 min. We also describe a method to ensure the long-term shelf stability of the ingredients. These results encourage further development of the AVF/APB formulation. Studies with APB and an alternative BZD, midazolam (MDZ), were not as promising due to a kinetic bottleneck following the enzyme reaction.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114250"},"PeriodicalIF":11.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093655","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

Synergistic enhancement of anti-migraine efficacy through supramolecular self-assembly of tizanidine with meloxicam 替扎尼定与美洛昔康超分子自组装协同增强抗偏头痛疗效

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-20 DOI: 10.1016/j.jconrel.2025.114248

Di Wu , Chen Chen , Wei Chen , Lin Fu , Gang Chen , Na Wang , Ting Wang , Xin Huang , Hongxun Hao

{"title":"Synergistic enhancement of anti-migraine efficacy through supramolecular self-assembly of tizanidine with meloxicam","authors":"Di Wu , Chen Chen , Wei Chen , Lin Fu , Gang Chen , Na Wang , Ting Wang , Xin Huang , Hongxun Hao","doi":"10.1016/j.jconrel.2025.114248","DOIUrl":"10.1016/j.jconrel.2025.114248","url":null,"abstract":"<div><div>Migraine, a debilitating medical condition that affects a significant portion of the population, presents a complex challenge in therapeutic management. Drug–drug cocrystallization based on supramolecular self-assembly offers a promising strategy, as it not only improves the physicochemical properties of active pharmaceutical ingredients, but also unlocks their synergistic clinical potential. In this study, supramolecular self-assemblies of tizanidine and meloxicam were designed through crystal engineering to explore their combined clinical value in anti-migraine therapy. The resulting multicomponent crystal, tizanidine-meloxicam, was thoroughly characterized by crystallography, spectroscopy, and thermal analysis. It forms a stable charge-assisted hydrogen bond supramolecular network, exhibiting ∼60 % improved solubility over tizanidine and ∼ 10-fold enhancement over meloxicam. In a rat migraine model, it achieved 100 % complete remission, with sustained analgesia 1.3 times greater than the physical mixture (<em>P</em> < 0.05). Furthermore, solution chemistry results indicate that the enhanced therapeutic performance of tizanidine-meloxicam salt can be attributed to its sustained release rate, higher equilibrium solubility, distinct molecular conformation, and stronger interactions between the two compounds. Additionally, tizanidine-meloxicam salt could form uniform and stable molecular clusters in aqueous solution, which could further enhance its efficacy and stability. This study demonstrates that pharmaceutical multicomponent crystals is a significant strategy for the development of novel formulations with improved efficacy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114248"},"PeriodicalIF":11.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093720","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

Harnessing engineered adaptive nanoparticles to modulate macrophages for treating corneal alkali burns 利用工程自适应纳米颗粒调节巨噬细胞治疗角膜碱烧伤

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-20 DOI: 10.1016/j.jconrel.2025.114253

Xianyan Qin , Luhan Zhang , Xinyu Wang , Jiayu Meng , Yang-Bao Miao , Qin Wang , Liang Zou , Qingwen Yang , Lingxi Jiang , Yi Shi

{"title":"Harnessing engineered adaptive nanoparticles to modulate macrophages for treating corneal alkali burns","authors":"Xianyan Qin , Luhan Zhang , Xinyu Wang , Jiayu Meng , Yang-Bao Miao , Qin Wang , Liang Zou , Qingwen Yang , Lingxi Jiang , Yi Shi","doi":"10.1016/j.jconrel.2025.114253","DOIUrl":"10.1016/j.jconrel.2025.114253","url":null,"abstract":"<div><div>Corneal alkali burns represent a severe ophthalmic emergency characterized by progressive inflammation, impaired epithelial regeneration, and pathological neovascularization, posing significant clinical challenges. Conventional topical therapies are hindered by rapid precorneal clearance and limited corneal penetration. To overcome these limitations, we designed adaptive nanoparticles (PDNPs) formed by the self-assembly of polysialic acid (PSA)-dexamethasone (Dex) <em>via</em> acid-sensitive hydrazone linkages. Upon topical administration, PSA-mediated Siglec-E recognition enabled selective anchoring of PDNPs to infiltrating corneal stromal macrophages, which then undergo chemotaxis-directed migration into deeper inflamed tissues, enhancing ocular surface retention and drug penetration. In the acidic microenvironment of the injured cornea, PDNPs undergo controlled Dex release, enabling precise spatiotemporally modulation of macrophages. In mice model of alkali injury, PDNPs significantly prolonged ocular surface retention and improved stromal drug distribution. Moreover, the treatment of PDNPs remarkedly accelerated corneal re-epithelialization, restored stromal transparency, reduce corneal edema and inhibit neovascularization. Mechanistic study indicated that PDNPs alleviated the corneal injury by effectively inhibited of the MAPK/NF-κB signaling pathway, a key axis in corneal inflammation. Overall, PDNPs demonstrated excellent therapeutic efficacy and tolerability for potential application as a novel platform for modulating inflammatory ocular surface diseases.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114253"},"PeriodicalIF":11.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089019","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

Probiotic encapsulation strategies for controlled intestinal delivery and microbiome dysbiosis therapy 控制肠道输送和微生物群失调治疗的益生菌包封策略

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-20 DOI: 10.1016/j.jconrel.2025.114252

Yilin You , Hongyun Lu , Yuxi Wang , Bijie Wang , Qihe Chen , Ying Shi

{"title":"Probiotic encapsulation strategies for controlled intestinal delivery and microbiome dysbiosis therapy","authors":"Yilin You , Hongyun Lu , Yuxi Wang , Bijie Wang , Qihe Chen , Ying Shi","doi":"10.1016/j.jconrel.2025.114252","DOIUrl":"10.1016/j.jconrel.2025.114252","url":null,"abstract":"<div><div>Probiotics have garnered significant interest due to their diverse and vital roles in promoting intestinal health. However, several challenges continue to impede their clinical efficacy, including the preservation of bioactivity during oral administration, effective targeting of intestinal lesions, modulation of the gut microenvironment, and extension of colonization time. This review offers a comprehensive overview of biomaterial-based encapsulation strategies for targeted probiotic delivery to the intestine. Particular attention is given to the factors that govern the selection of probiotic strains and to the role of microbial interactions in shaping the design of oral delivery systems. Furthermore, we highlight the critical challenges associated with oral delivery, summarize the functional materials and their underlying mechanisms, and provide a comparative analysis of their strengths and limitations. Key factors influencing probiotic strain selection and encapsulation methods are examined in detail. The review also highlights major gastrointestinal barriers—such as variable pH, digestive enzymes, reactive oxygen species (ROS), colonization resistance, rapid transit time, and mucus layer degradation—and outlines corresponding mitigation strategies. Recent progress in targeted delivery systems and immune modulation enabled by encapsulated probiotics is discussed, along with a survey of current therapeutic applications. Finally, emerging trends and ongoing challenges in the field are explored, emphasizing the promising potential of encapsulated probiotic systems in restoring microbiome homeostasis and treating dysbiosis-related disorders.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114252"},"PeriodicalIF":11.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089020","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

Expression of concern to “Mannosylated solid lipid nanoparticles as vectors for site-specific delivery of an anti-cancer drug” [Journal of Controlled Release (2010, DOI: 10.1016/j.jconrel.2010.09.003] 表达对“甘露糖基化固体脂质纳米颗粒作为抗癌药物位点特异性递送载体”的关注[Journal of control Release (2010, DOI: 10.1016/j.jconrel.2010.09.003]

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-09-19 DOI: 10.1016/j.jconrel.2025.114249

引用次数: 0

Hierarchical ROS-scavenging platform breaks vicious cycle of stem cell senescence, angiogenesis arrest, and immune dysregulation in diabetic wounds 分层ros清除平台打破了糖尿病创面干细胞衰老、血管生成停滞和免疫失调的恶性循环

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-19 DOI: 10.1016/j.jconrel.2025.114247

Shuo Wang , Jiaheng Liang , Rui Ding , Weihao Zhao , Jianhong Zhang , Pandi Peng , Jin Chai , Yibo Yan , Peng Li

{"title":"Hierarchical ROS-scavenging platform breaks vicious cycle of stem cell senescence, angiogenesis arrest, and immune dysregulation in diabetic wounds","authors":"Shuo Wang , Jiaheng Liang , Rui Ding , Weihao Zhao , Jianhong Zhang , Pandi Peng , Jin Chai , Yibo Yan , Peng Li","doi":"10.1016/j.jconrel.2025.114247","DOIUrl":"10.1016/j.jconrel.2025.114247","url":null,"abstract":"<div><div>Diabetic chronic wounds represent a formidable clinical challenge, driven by a pathological vicious cycle of reactive oxygen species (ROS)-induced oxidative stress, stem cell senescence, angiogenesis arrest, and immune dysregulation. Herein, we developed a hierarchical ROS-scavenging platform integrating nanoscale calcium hydride (CaH₂) within a microneedle (MN) patch to disrupt this degenerative cascade. Upon dissolution in wound exudate, CaH₂ nanoparticles react with water to generate sustained release of hydrogen gas (H₂) and calcium ions (Ca<sup>2+</sup>). The liberated H₂ directly neutralizes cytotoxic ROS, thereby reversing stem cell senescence and restoring their paracrine secretion of pro-angiogenic factors, while concomitantly reprogramming macrophages toward pro-regenerative M2 phenotypes. Simultaneously, Ca<sup>2+</sup> synergizes with H₂ to activate endothelial cell migration and tubulogenesis, fostering robust vascular network formation. By concurrently resolving oxidative stress, stem cell senescence, angiogenesis arrest, and immune dysregulation, the CaH₂-MN system breaks the vicious cycle to reshape the wound microenvironment into a pro-regenerative state. In diabetic murine models, this approach accelerated wound closure, enhanced neovascularization, and reduced inflammatory infiltration. This multiscale intervention paradigm provides a blueprint for intercepting pathological cascades in diabetic wounds.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114247"},"PeriodicalIF":11.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084282","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

FormulationMM: A universal computer-driven drug formulation platform FormulationMM：一个通用的计算机驱动药物配方平台

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-19 DOI: 10.1016/j.jconrel.2025.114237

Yunsen Zhang , Chenyu Lin , Zhongmin Zhao , Zheng Wu , Hao Zhong , Nannan Wang , Tianshu Lu , Huanle Xu , Defang Ouyang

{"title":"FormulationMM: A universal computer-driven drug formulation platform","authors":"Yunsen Zhang , Chenyu Lin , Zhongmin Zhao , Zheng Wu , Hao Zhong , Nannan Wang , Tianshu Lu , Huanle Xu , Defang Ouyang","doi":"10.1016/j.jconrel.2025.114237","DOIUrl":"10.1016/j.jconrel.2025.114237","url":null,"abstract":"<div><div>Classical computer-aided drug design answers “Will this ligand bind?”, whereas computer-driven drug formulation answers the downstream but equally critical question “How can this drug be physically formulated and delivered?”, thereby bridging the long-standing gap between molecular modeling and drug formulation science through physics-based and fully automated multiscale simulation. To build this bridge, we introduce FormulationMM, an innovative platform utilizing real-world driven molecular modeling to explore drug formulation mechanisms. FormulationMM features a pharmaceutical formulation algorithm, an integrated excipient database, and robust modeling protocols, ensuring a streamlined workflow for the generation, simulation, and analysis of drug formulation. It automatically generates force field parameters for drug molecules and excipients, supporting six formulation types: cyclodextrin-drug inclusion, micelles, liposomes, solid dispersions, self-assembling drug nanoparticles, and transmembrane drug delivery systems. Our results closely match experimental findings and demonstrate high predictive accuracy and reliability. FormulationMM, accessible through a continuously updated website (<span><span>https://formulationmm.computpharm.org</span><svg><path></path></svg></span>), offers a practical platform to support drug formulation research and development, with the potential to advance the growing field of computer-driven drug formulation.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114237"},"PeriodicalIF":11.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084168","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 general nanoplatform for nucleotide drug delivery: From molecular binding to antiviral therapy 核苷酸药物传递的通用纳米平台：从分子结合到抗病毒治疗

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-18 DOI: 10.1016/j.jconrel.2025.114245

Zheng Zhou , Fan Zhang , Xiang Li , Yina Zhang , Xiahong Xie , Qifan Liu , Pingan Xia , Xinping Wang , Mingzhou Ye

{"title":"A general nanoplatform for nucleotide drug delivery: From molecular binding to antiviral therapy","authors":"Zheng Zhou , Fan Zhang , Xiang Li , Yina Zhang , Xiahong Xie , Qifan Liu , Pingan Xia , Xinping Wang , Mingzhou Ye","doi":"10.1016/j.jconrel.2025.114245","DOIUrl":"10.1016/j.jconrel.2025.114245","url":null,"abstract":"<div><div>Nucleoside-based agents represent an important class of therapeutics for viral infections and malignancies. Their pharmacologically active forms, nucleoside triphosphates (TPs), exhibit high polarity and negative charge severely limiting cellular uptake and intracellular utilization. While prodrug strategies used in clinical practice often exhibit limited activation and efficacy, nanocarrier-based TP delivery offers a promising alternative; however, efficient encapsulation of these highly hydrophilic small molecules remains a great challenge. To address this, we developed a rationally designed polymeric carrier PGB, featuring alternating phenylboronic acid and guanidinium groups that bind to conserved nucleotide motifs through multivalent interactions. This design achieves an association constant up to 5.19 × 10<sup>8</sup> with ATP at pH 7.4, facilitates efficient cytosolic delivery, and enhances antiviral efficacy across multiple viral infection models. In an H1N1-infected mouse model, the nanoparticle formulation demonstrated a markedly improved pharmacokinetic profile compared to the antiviral drug Molnupiravir, effectively suppressed viral replication, reduced pulmonary inflammatory cell infiltration, and preserved lung structure and function. Our study successfully achieved the efficient loading and intracellular delivery of hydrophilic molecules, providing a versatile and broadly applicable platform for nucleotide drug delivery.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114245"},"PeriodicalIF":11.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084169","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

An ionic liquid nanoemulsion transdermal delivery system for targeted melanoma therapy 靶向黑色素瘤治疗的离子液体纳米乳透皮给药系统

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-18 DOI: 10.1016/j.jconrel.2025.114243

Rongtian Lin , Wenjuan Ding , Chuang Lei , Weiliang Liu , Jiahao Li , Jianling Hu , Jiaping Qian , Huijing Li , Yanchao Wu , Jiaheng Zhang

{"title":"An ionic liquid nanoemulsion transdermal delivery system for targeted melanoma therapy","authors":"Rongtian Lin , Wenjuan Ding , Chuang Lei , Weiliang Liu , Jiahao Li , Jianling Hu , Jiaping Qian , Huijing Li , Yanchao Wu , Jiaheng Zhang","doi":"10.1016/j.jconrel.2025.114243","DOIUrl":"10.1016/j.jconrel.2025.114243","url":null,"abstract":"<div><div>Melanoma is the deadliest form of skin malignancy. The existing transdermal treatment strategies are difficult to achieve effective concentration of drugs in deep-seated tumors, which seriously affects the effect of percutaneous treatment. The low efficacy of medications for treating melanoma and their percutaneous penetration into tumor tissues are the urgent problems to be solved in percutaneous treatment of skin malignancies. In this work, two dacarbazine/benzothiocycloheptane (DTIC/<strong>14</strong>) couplets were designed and synthesized, among which compound HIT-1 exhibited significantly cytotoxicity to B16-F10 (IC<sub>50</sub> = 7.86 μM), and 10.3-fold stronger than DTIC. HIT-1 could significantly induce apoptosis and G0/G1 phase arrest of B16-F10 cells, showing a good anti-melanoma effect. Three self-assembled nanoemulsions (HIT-1/PM-MEs) were prepared on the basis of molecular simulation, among which HIT-1/PM-ME-1-1 had the best transdermal drug delivery effect. HIT-1/PM-ME-1-1 was not only 11.8-fold stronger than DTIC in terms of anti-B16-F10 activity, but also a good regulator of mRNA and protein expression of DNAJB1, HSPA1B, p53, Bcl-2 and Cleaved-caspase 3. Furthermore, the HIT-1/PM-ME-1-1 transdermal delivery system showed optimal antitumor effects and stimulated antitumor immune response. Altogether, these results strongly support that this transdermal drug delivery system provides a valuable new strategy for the treatment of cutaneous melanoma.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114243"},"PeriodicalIF":11.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084375","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

Fluorinated albumin nanocages dually target CAFs and tumor cells to potentiate bladder cancer chemoimmunotherapy 氟化白蛋白纳米笼双重靶向caf和肿瘤细胞，以增强膀胱癌的化学免疫治疗

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-17 DOI: 10.1016/j.jconrel.2025.114246

Zhijun Miao , Anan Xu , Gang Shen , Siyi Tang , Jie Luo , Jiajian Yang , Zhe Chen , Jinxian Pu , Tao Yang

{"title":"Fluorinated albumin nanocages dually target CAFs and tumor cells to potentiate bladder cancer chemoimmunotherapy","authors":"Zhijun Miao , Anan Xu , Gang Shen , Siyi Tang , Jie Luo , Jiajian Yang , Zhe Chen , Jinxian Pu , Tao Yang","doi":"10.1016/j.jconrel.2025.114246","DOIUrl":"10.1016/j.jconrel.2025.114246","url":null,"abstract":"<div><div>Immunogenic cell death (ICD) induced by chemotherapeutics holds promise for cancer therapy, but limited drug penetration across the bladder mucosa and an immune-excluded tumor microenvironment (TME) have hindered success in bladder cancer. Here, we develop fluorinated albumin nanocages as transmucosal delivery vesicles that concurrently target cancer-associated fibroblasts (CAFs) and tumor cells to potentiate chemoimmunotherapy. Surface fluorination enables mucosal penetration, while recognition of secreted protein acidic and cysteine-rich (SPARC) protein ensures selective uptake by CAFs and tumor cells. Encapsulated chemotherapeutics enhance ICD through inhibition of the Bcl-2 pathway, promoting tumor cell death. Simultaneous CAF disruption reduces stromal fibrosis, facilitating anti–PD-L1 antibody delivery and T-cell infiltration. This dual-targeting strategy synergizes ICD with immune checkpoint blockade to eradicate bladder tumors by recruiting cytotoxic T cells and suppressing immunosuppressive phenotypes. <em>Ex vivo</em> studies in freshly resected human bladder tumors further validated the translational potential. Our findings highlight the fluorinated albumin nanocages as a versatile transmucosal platform to remodel the tumor–stroma axis and amplify chemoimmunotherapy in bladder cancer.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114246"},"PeriodicalIF":11.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077350","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