Journal of Controlled Release最新文献

{"title":"Biodegradable nanofibrous scaffolds enhance standard of care for glioblastoma via localized targeted therapy","authors":"Ryan N. Woodring ,&nbsp;Elizabeth G. Graham-Gurysh ,&nbsp;Sophie E. Mendell ,&nbsp;Kevin E. Shilling ,&nbsp;Nicole Rose Lukesh ,&nbsp;Katie A. Hipp ,&nbsp;William C. Zamboni ,&nbsp;Eric M. Bachelder ,&nbsp;Kristy M. Ainslie","doi":"10.1016/j.jconrel.2025.114225","DOIUrl":"10.1016/j.jconrel.2025.114225","url":null,"abstract":"<div><div>Combination therapy is a well-established clinical strategy for treating aggressive cancers, but its success has not translated to patients with glioblastoma <em>multiforme</em> (GBM)—the most aggressive malignancy of the central nervous system. In this study, we evaluated the effects of combining temozolomide (TMZ), the standard chemotherapeutic agent for GBM, with several candidate targeted therapies to improve current outcomes in a mouse model of GBM resection and recurrence. In vitro, the EGFR inhibitor, erlotinib (ERL), emerged as the most promising combination drug across a diverse panel of GBM cells. In vivo, the therapeutic response was enhanced through localized delivery. ERL was encapsulated into electrospun acetalated dextran (Ace-DEX) scaffolds (Ace-ERL), a biodegradable and biocompatible polymer system that enables tunable degradation and controlled drug release. Local delivery of Ace-ERL to the resection cavity improved the pharmacokinetic profile and, when combined with systemic TMZ, significantly enhanced survival in a patient-derived xenograft mouse model. These findings support a novel translational approach to leverage combination therapy in GBM by pairing targeted delivery with standard chemotherapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114225"},"PeriodicalIF":11.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043101","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}

{"title":"Mucosal and transdermal delivery strategies for mRNA: Transforming the clinical applications","authors":"Lirong Wang ,&nbsp;Hongzhang Deng","doi":"10.1016/j.jconrel.2025.114221","DOIUrl":"10.1016/j.jconrel.2025.114221","url":null,"abstract":"<div><div>Messenger RNA (mRNA)-based therapies have demonstrated remarkable potential for the prevention and treatment of a wide range of diseases in clinical applications, owing to the unique properties of mRNA. In recent years, mRNA delivery has expanded beyond traditional needle-based injections, with the development of various non-invasive strategies aimed at enhancing patient compliance, reducing infection risks, and eliminating injection-related discomfort. Among them, mucosal delivery and transdermal delivery as two core non-invasive strategies, have become key directions for advancing the clinical translation of mRNA. In this review, we comprehensively summarize the existing mucosal and transdermal delivery mRNA delivery strategies, including transdermal, oral, pulmonary, nasal, and vaginal non-invasive delivery strategies, focusing on the unique advantages of each strategy, the physiological barriers it faces, and its latest research progress. Additionally, we present key biomedical applications of mRNA therapeutics currently in clinical trials, such as those targeting infectious diseases, cancers, and cardiovascular disorders. Finally, we offer a perspective on the remaining challenges and future directions for mucosal and transdermal delivery mRNA delivery. Despite these hurdles, we believe that advancing these strategies holds significant promise for transforming clinical practice and improving patient outcomes.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114221"},"PeriodicalIF":11.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025419","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}

{"title":"Neutrophil extracellular traps: Formation, pathological roles, and nanoparticle-based therapeutic targeting strategies","authors":"Nina Filipczak ,&nbsp;Satya Siva Kishan Yalamarty ,&nbsp;Xiang Li ,&nbsp;Tanvi Vinod Pathrikar ,&nbsp;Roshani Pinapati ,&nbsp;Bijal Vanjara ,&nbsp;Vladimir Torchilin","doi":"10.1016/j.jconrel.2025.114220","DOIUrl":"10.1016/j.jconrel.2025.114220","url":null,"abstract":"<div><div>Neutrophil extracellular traps (NETs) are large, web-like DNA structures released by neutrophils, coated with histones and antimicrobial proteins. They serve as a crucial defense mechanism for neutrophils against microbial invasion, playing a significant role in eliminating microorganisms such as bacteria, fungi, and viruses. While NETs are primarily recognized for their role in microbial defense, growing evidence indicates that excessive NET formation, triggered by physical and chemical stimuli, pathogens, or pathological factors, can worsen inflammation and cause organ damage. Understanding NETs' presence in various tissues and body fluids is crucial for elucidating their contribution to disease etiopathogenesis. By designing nanoparticles that can either prevent NET formation or facilitate their degradation, researchers aim to mitigate the harmful effects of excessive NETs. These nanotechnological interventions can be tailored to specifically target the molecular components of NETs, enhancing treatment precision and efficacy. Furthermore, nanoparticles can deliver therapeutic agents directly to inflammation sites, reducing systemic side effects and improving patient outcomes. This review summarizes the role of NETs in various pathologies, focusing on strategies to inhibit NETosis, including mechanisms of pathogen evasion, and the use of nanodelivery systems to enhance the efficiency of NETs inhibition or removal.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114220"},"PeriodicalIF":11.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043022","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}

{"title":"Organoids as predictive platforms: advancing disease modeling, therapeutic innovation, and drug delivery systems","authors":"Ting Huang ,&nbsp;Weitao Huang ,&nbsp;Qiong Bian","doi":"10.1016/j.jconrel.2025.114222","DOIUrl":"10.1016/j.jconrel.2025.114222","url":null,"abstract":"<div><div>As three-dimensional (3D), physiologically relevant models, organoids are rapidly becoming revolutionary platforms in biomedical research. With their ability to recapitulate tissue architecture, disease heterogeneity, and patient-specific therapeutic responses, organoids have revolutionized applications from disease modeling to precision medicine. In this review, we discuss recent advancements in engineering organoids through integrations with microfluidics, genetic editing, bioprinting, and artificial intelligence, which can collectively enhance microenvironmental control, functional maturation, and scalability. The multifaceted biomedical applications of organoids across disease modeling, regenerative medicine, drug evaluation, and precision oncology are also summarized. We further highlight the role of organoids in advancing drug delivery systems by validating targeting efficiency, therapeutic efficacy, and safety profiles. Finally, we address persistent challenges in vascularization, immune integration, and standardization while outlining future strategies for interdisciplinary innovation to harness organoids' full potential in reshaping biomedicine.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114222"},"PeriodicalIF":11.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043384","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}

{"title":"Effects of nanoparticle physicochemical properties on macrophage polarization","authors":"Haochen Lin ,&nbsp;Zheng Li ,&nbsp;Ivan V. Zelepukin ,&nbsp;Sergey M. Deyev ,&nbsp;Xiangliang Yang ,&nbsp;Zifu Li","doi":"10.1016/j.jconrel.2025.114215","DOIUrl":"10.1016/j.jconrel.2025.114215","url":null,"abstract":"<div><div>Tumor-associated macrophages (TAMs) are crucial in regulating tumor immune microenvironment (TIME), tumor development and tumor therapy. Nanoparticles, as traditional tumor targeting drug delivery systems, of which the intrinsic immunomodulatory potential has been gradually explored by modulating physicochemical properties. This review systematically summarizes advancements in polarizing macrophages by regulating physicochemical properties of nanoparticles including size, morphology, surface properties, stiffness, and other factors. Furthermore, the polarization mechanisms are expounded via biochemical and mechanical signaling pathways. Size of nanoparticles affects macrophage polarization through lysosomal stress and membrane interaction; morphology of nanoparticles impacts macrophage polarization through inducing membrane curvature or modulating cellular metabolism; surface properties of nanoparticles effects macrophage polarization through enhancing nanoparticle binding ability to cell membrane; stiffness of nanoparticles polarize macrophages through activating mechanosensitive ion channels and inducing deformation of membrane; other properties of nanoparticles effects macrophage polarization via glycolysis, oxidative phosphorylation, etc. These outcomes contribute to the optimization of nanomedicine physicochemical properties for tumor immunotherapy by regulating polarization of TAMs and reshaping the immunosuppressive TIME, thereby driving the development of precision immuno-oncology for various malignancies.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114215"},"PeriodicalIF":11.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017167","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}

{"title":"Lipid nanoparticle mediated delivery of dsDNA to the murine retina","authors":"Rachel L. Fehrman ,&nbsp;Deepak Sahel ,&nbsp;Gaurav Sahay ,&nbsp;Daniel M. Lipinski ,&nbsp;Renee C. Ryals","doi":"10.1016/j.jconrel.2025.114194","DOIUrl":"10.1016/j.jconrel.2025.114194","url":null,"abstract":"<div><div>Gene therapy has become a successful tool for treating inherited retinal diseases (<strong>IRDs</strong>). To date, recombinant adeno-associated virus (<strong>rAAV</strong>)- mediated delivery is the preferred method for gene transfer; however, its limited payload capacity restricts its use for treatment to causative loci under 5 kb. Recent advances in gene therapy tools have demonstrated the success of non-viral delivery vectors with lipid-based nanoparticles (<strong>LNPs</strong>) at the forefront. Owing to the SARS-CoV-2 vaccine, LNPs have already demonstrated clinical safety, however in regard to IRDs, the LNPs are limited to RPE and Muller glia cells, and their application has been limited to transient RNA delivery. Previously, we have reported that the introduction of N-Hydroxysuccinamide (NHS) functionalized PEG lipid (DSPE-PEG2K-NHS) to the LNPs (called LNPx) improved their overall transfection rate and widened their transfection efficiency to include not only RPE but photoreceptor cells. Taken together, this could expand LNP utility and allow for the treatment of many prevalent IRDs. Herein, we utilized LNPx to demonstrate the feasibility and safety of dsDNA delivery after subretinal injection into the murine retina, through a combination of multimodal in vivo imaging and post-mortem histology.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114194"},"PeriodicalIF":11.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017547","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}

{"title":"Novel TNF-α-targeting mRNA therapy for sustained psoriasis treatment and relapse prevention by suppressing IL-15-TRM signaling","authors":"Xi Li ,&nbsp;Xianyu Shao ,&nbsp;Xiangzheng Li ,&nbsp;Qingqing Chen ,&nbsp;Yu Zang ,&nbsp;Jingyi Wang ,&nbsp;Yong Yang ,&nbsp;Lei Qiang ,&nbsp;Ang Lin ,&nbsp;Yuan He","doi":"10.1016/j.jconrel.2025.114218","DOIUrl":"10.1016/j.jconrel.2025.114218","url":null,"abstract":"<div><div>Psoriasis is an autoimmune skin disease that substantially impairs patients' quality of life and presents clinical challenges due to frequent relapses and adverse effects associated with conventional therapies, including glucocorticoids and immunosuppressants. Although tumor necrosis factor-alpha (TNF-α) inhibitors are widely used as front-line treatments, safer alternatives remain imperative. Here, RET-1-mRNA-LNP, a novel mRNA-based TNF-α inhibitor, was developed and comprehensively evaluated for its therapeutic efficacy in imiquimod (IMQ)-induced psoriasis and relapse mouse model. RET-1-mRNA-LNP demonstrated superior efficacy in reducing erythema, scaling, and epidermal hyperplasia, along with a significant suppression of Th17 cell activity and other immune cell infiltration into lesional skin. Mechanistically, RET-1-mRNA-LNP delayed psoriasis recurrence by suppressing IL-15 production and generation of tissue-resident memory T (T_RM) cells. These findings provide novel insights and a theoretical foundation for developing TNF-α-targeting mRNA-based therapeutics for psoriasis treatment, evoking potential applications in other autoimmune diseases characterized by excessive TNF-α production.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114218"},"PeriodicalIF":11.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017548","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}

{"title":"Hydrodynamic focusing to synthesize lipid-based nanoparticles: Computational and experimental analysis of chip design and formulation parameters","authors":"Mahmoud Abdelkarim ,&nbsp;Amr Abostait ,&nbsp;Samuel Czitrom ,&nbsp;Sarah McColman ,&nbsp;Ilhaan Ahmed ,&nbsp;Charles Chan Wai Wong ,&nbsp;Dario Bogojevic ,&nbsp;Mohamed Abdelgawad ,&nbsp;Hagar I. Labouta","doi":"10.1016/j.jconrel.2025.114192","DOIUrl":"10.1016/j.jconrel.2025.114192","url":null,"abstract":"<div><div>Microfluidic hydrodynamic focusing (HF) has emerged as a powerful platform for the controlled synthesis of lipid nanoparticles (LNPs) and liposomes, offering superior precision, reproducibility, and scalability compared to traditional batch methods. However, the impact of HF inlet configuration and channel geometry on nanoparticle formation remains poorly understood. In this study, we present a comprehensive experimental and computational analysis comparing 2-inlet (2-way) and 4-inlet (4-way) HF designs across various sheath inlet angles (45°, 90°, 135°) and cross-sectional geometries (square vs. circular), assessing their influence on particle size, polydispersity index (PDI), and percentage encapsulation efficiency (%EE) of siRNA and FITC-Dextran. Using 3D-printed microfluidic chips, empty and loaded liposomes and LNPs were synthesized across a range of lipid concentrations (1–8 mg/mL) and total flow rates (0.12–16 mL/min). Computational fluid dynamics (CFD) simulations revealed significant differences in mixing profiles and ethanol diffusion across configurations, correlating with observed nanoparticle properties. Interestingly, 2-way focusing outperformed 4-way designs at low flow rates due to broader diffusive interfaces, while 4-way 45° configurations provided superior control over nanoparticle formation at high flow rates. Circular channels produced smaller, more uniform nanoparticles than square channels, likely due to symmetric flow patterns and reduced stagnation zones. Higher lipid concentrations decreased PDI and improved encapsulation, particularly for siRNA-loaded LNPs. Encapsulation efficiencies were similar across most configurations; however, a statistically significant increase was observed in the 4-way 135° design at 4 mL/min. This likely reflects size-related effects rather than a specific advantage of the configuration. Furthermore, LNPs produced at higher flow rates exhibited enhanced cellular uptake, attributed to their smaller particle size. Overall, our results demonstrate that optimal nanoparticle synthesis via HF is governed by an interplay of flow rate, inlet geometry, and formulation parameters (nanoparticle type and lipid concentration) rather than the number of inlets alone. This study provides a design framework for selecting HF configurations tailored to specific throughput and encapsulation requirements in therapeutic nanocarrier production.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114192"},"PeriodicalIF":11.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009331","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}

{"title":"Self-immolative fluorinated nanotheranostics amplifying 19F MRI signals for tumor-specific imaging and photodynamic therapy","authors":"Ruling Zhang ,&nbsp;Kai Wang ,&nbsp;Wenqing Xiao ,&nbsp;Dalin Wu ,&nbsp;Zhong Cao","doi":"10.1016/j.jconrel.2025.114217","DOIUrl":"10.1016/j.jconrel.2025.114217","url":null,"abstract":"<div><div>Fluorine-19 magnetic resonance imaging (¹⁹F MRI) offers distinct advantages, including background-free signal detection, quantitative analysis, and deep tissue penetration. However, its application is currently limited by challenges associated with existing ¹⁹F MRI contrast agents, such as short transverse relaxation times (T₂), limited imaging sensitivity, and suboptimal biocompatibility. To overcome these limitations, a glutathione (GSH)-responsive triblock copolymer (PB7), featuring self-immolative characteristics, has been developed. In aqueous solution, PB7 can spontaneously self-assemble into a ¹⁹F MRI contrast agent (SPTF), which exhibits a long T₂ relaxation time and GSH-responsive T₂ prolongation. Notably, during the self-assembly process of PB7, the photosensitizer Chlorin e6 (Ce6) can be encapsulated inside of the hydrophobic domain of SPTF, resulting in the formation of a multifunctional nanotheranostic agent (Ce6@SPTF). Ce6@SPTF is able to undergo structural disintegration in response to elevated GSH levels at the tumor site, leading to the dissociation of fluorinated segments and a marked amplification of the ¹⁹F MRI signal. Concurrently, the controlled release of Ce6 generates high levels of reactive oxygen species (ROS) under laser irradiation, enabling effective <em>in vivo</em> ablation of breast tumors. This study presents a promising strategy to effectively combine ¹⁹F MRI with therapeutic interventions.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114217"},"PeriodicalIF":11.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009356","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}

{"title":"Pulmonary delivery of small circular RNA vaccines for influenza prevention","authors":"Yu Zhang ,&nbsp;You Xu ,&nbsp;Wei Tang ,&nbsp;Shurong Zhou ,&nbsp;Xiang Liu ,&nbsp;Zitong Wang ,&nbsp;Guizhi Zhu","doi":"10.1016/j.jconrel.2025.114198","DOIUrl":"10.1016/j.jconrel.2025.114198","url":null,"abstract":"<div><div>Lipid nanoparticles (LNPs) have played an instrumental role in the delivery of RNA therapeutics and vaccines, including the emerging class of synthetic circular RNA (circRNA). Pulmonary vaccines hold the potential to prevent various respiratory infectious diseases, such as influenza caused by influenza infection. Here, we report the pulmonary delivery of LNPs loaded with highly stable small circRNA vaccine for influenza prevention. Upon intratracheal (<em>i.t.</em>) instillation of circRNA LNPs into mice, circRNA was efficiently retained in the lung and was delivered to antigen-presenting cells (APCs). To elicit immune responses against influenza, we designed and synthesized a small circRNA-M2e encoding matrix protein 2 ectodomain (M2e), a highly conserved but poorly immunogenic antigen from influenza A. <em>I.t.</em> administration of circRNA-M2e LNPs elicited robust anti-M2e immunity in both young adult mice and 18-month-old aged mice. As a result, pulmonary delivery of LNPs loaded with circRNA-M2e vaccine protected mice from lethal influenza challenge, without significant adverse side effects. Collectively, these results demonstrate the potential of pulmonary circRNA vaccines for respiratory infectious diseases such as influenza.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114198"},"PeriodicalIF":11.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009420","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}