Journal of Controlled Release最新文献

{"title":"Large and low-PEG lipid nanoparticles enable efficient dendritic cell targeting for potent mRNA Cancer vaccines","authors":"Xiaolan Xu ,&nbsp;Jiahao An ,&nbsp;Dan Bai ,&nbsp;Yuanchao Xu ,&nbsp;Tingting Wu ,&nbsp;Hua Yang ,&nbsp;Yueyue Yan ,&nbsp;Shaojun Yang ,&nbsp;Zifan Wei ,&nbsp;Yuchen Yao ,&nbsp;Qian Liu ,&nbsp;Tao Xu ,&nbsp;Lan Zhu","doi":"10.1016/j.jconrel.2026.114680","DOIUrl":"10.1016/j.jconrel.2026.114680","url":null,"abstract":"<div><div>Efficient delivery of messenger RNA (mRNA) to dendritic cells (DCs) remains a major challenge limiting the efficacy of mRNA cancer vaccines. Here, we report a large-sized lipid nanoparticle (LLNP) platform specifically engineered for enhanced DC targeting. By reducing PEG–lipid content to 0.3% and proportionally increasing the concentrations of structural lipids and mRNA sixfold relative to the Moderna classic formulation, we generated LLNPs with enlarged size and optimized surface properties that favor DC uptake. Following intravenous administration, LLNPs achieved markedly enhanced mRNA expression in DCs, with ∼82% of GFP⁺ cells identified as DCs and ∼ 44% of CD11c⁺ DCs expressing GFP. LLNPs also promoted DC maturation and antigen presentation. LLNP-mediated delivery of HPV16 E6E7 mRNA elicited robust effector and memory cytotoxic T lymphocyte responses, enabling effective tumor regression at doses as low as 1 μg. Both conventional type 1 dendritic cells (cDC1) and conventional type 2 dendritic cells contributed to antigen presentation, with cDC1 playing the predominant role. Compared with BioNTech's RNA–lipoplex delivery platform, LLNPs demonstrated superior DC transfection, T cell activation, and antitumor efficacy. Collectively, these findings establish LLNPs as a robust and versatile platform for next-generation mRNA cancer vaccines with enhanced therapeutic potential.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114680"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098412","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":"Translational m-PBPK Modeling reveals active transcytosis as the pivotal mechanism for nanoparticle tumor delivery: Implications for dose optimization","authors":"Jinwei Zhu ,&nbsp;Hui Lin ,&nbsp;Kejie Wang ,&nbsp;Sasa Zhang ,&nbsp;Hua He ,&nbsp;Kun Hao","doi":"10.1016/j.jconrel.2026.114684","DOIUrl":"10.1016/j.jconrel.2026.114684","url":null,"abstract":"<div><div>The long-held assumption that passive diffusion governs nanomedicine entry into the tumors has been increasingly challenged, with accumulating evidence implicating transcytosis as an important route for nanoparticle transport across the tumor endothelium. However, quantitative comparisons of their relative contributions remain scarce. To address this gap, this study developed a minimal physiologically based pharmacokinetic (m-PBPK) model that integrates in vitro cellular kinetic data to quantitatively describe to tumor delivery of nanoparticles and to assess the relative contributions of diffusion- and transcytosis-mediated transport within a model-based context. The framework was evaluated using PEGylated gold nanoparticles (AuNPs) spanning a range of particle sizes and incorporated empirical size-parameter relationships to enable in vitro<em>-</em>in vivo translational analysis. Model simulations suggested that transcytosis-mediated processes account for the majority of tumor AuNP accumulation under the modeled physiological conditions (99.0 %, 95 % CI: 94.7 %–99.8 %), whereas passive diffusion contributed a smaller fraction under most conditions examined. Dose-dependent analysis further indicated a capacity-limited tumor accumulation behavior, with a threshold around 18 mg, beyond which increasing the dose to 100 mg resulted in only a modest (∼15 %) increase in tumor accumulation. Sensitivity analyses indicated that systemic exposure and endothelial intracellular trafficking behavior are key determinants influencing tumor delivery, whereas enhanced intracellular sequestration consistently reduced tumor accumulation across dose levels. Overall, the proposed m-PBPK framework provides mechanistically interpretable, proof-of-concept insights into nanoparticle tumor delivery, supporting quantitative assessment of transcytosis efficiency and dose-dependent accumulation behavior for hypothesis generation in nanomedicine development.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114684"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109924","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":"Smart hypoxia-responsive sulfated polysaccharides liposomes for controlled and targeted urokinase delivery in thrombotic therapy","authors":"Dingfu Wang ,&nbsp;Dan Li ,&nbsp;Xiaolin Liu ,&nbsp;Shixin Wang ,&nbsp;Yile Fan ,&nbsp;Ling Lu ,&nbsp;Chuanbin Shen ,&nbsp;Chunxia Li","doi":"10.1016/j.jconrel.2026.114669","DOIUrl":"10.1016/j.jconrel.2026.114669","url":null,"abstract":"<div><div>Thrombosis remains a leading cause of cardiovascular and cerebrovascular mortality worldwide. Plasminogen activators, notably urokinase and alteplase, have been established as standard thrombolytic agents in clinical practice. However, their therapeutic potential is severely compromised by rapid metabolic clearance, non-specific biodistribution, and associated hemorrhagic complications. Here, we designed a dual-functional nano drug delivery platform that leverages P-selectin overexpression on activated platelets and the characteristic hypoxic microenvironment at thrombotic sites for precision thrombolytic intervention. Specifically, we developed a hypoxia-responsive block (PAC) by conjugating polyguluronate sulfate (PGS, P-selectin targeting motif) with azobenzene-modified cholesterol, enabling urokinase encapsulation within PAC@UK liposomes. Under hypoxic conditions that mimic the thrombotic microenvironment, the reductive cleavage of azobenzene moieties initiated sustained urokinase release (96.41% cumulative release), while maintaining exceptional biocompatibility and demonstrating preferential targeting of activated platelets. Comprehensive <em>in vivo</em> validation across zebrafish, murine mesenteric, and carotid artery thrombosis models revealed markedly enhanced thrombolytic efficacy compared to free UK. This biomimetic nanoplatform represents a paradigm shift toward intelligent, site-specific thrombolytic intervention, offering substantial clinical promise for safer and more effective treatment of thrombotic disorders.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114669"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089553","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":"Intranasal delivery of peptide-modified quercetin liposomes suppresses neuroinflammation","authors":"Changfeng Yin ,&nbsp;Guanglin Liu ,&nbsp;Xiqian Yuan ,&nbsp;Yumeng Zhang ,&nbsp;Yushan Tian ,&nbsp;Xiao Li ,&nbsp;Ling'e Zhang ,&nbsp;Xiqun Jiang ,&nbsp;Huan Chen ,&nbsp;Hongwei Hou ,&nbsp;Qingyuan Hu","doi":"10.1016/j.jconrel.2026.114678","DOIUrl":"10.1016/j.jconrel.2026.114678","url":null,"abstract":"<div><div>Neuroinflammation, a central pathological mechanism in central nervous system disorders, remains challenging to treat due to the restrictive nature of the blood-brain barrier and poor drug delivery efficiency. In this study, we developed a novel intranasal brain-targeted delivery system by constructing peptide-modified quercetin liposomes (QuR-lipo). By using intranasal administration to bypass the blood-brain barrier, QuR-lipo demonstrated higher uptake and accumulation in the brain compared to unmodified liposomes. This system disrupts the vicious cycle between neuroinflammation and oxidative stress, thereby improving neurobehavioral outcomes. QuR-lipo displayed a uniform particle size distribution, high encapsulation efficiency, and sustained-release characteristics. In vitro studies showed that QuR-lipo enhanced intracellular drug accumulation by modulating endocytic pathways, effectively inhibited aberrant microglial activation, suppressed pro-inflammatory cytokine cascades, and scavenged reactive oxygen species. In a lipopolysaccharide-induced neuroinflammation animal model, intranasal delivery of QuR-lipo significantly increased brain drug concentration, improved spatial memory deficits and depression-like behaviors, and suppressed microglial activation. Mechanistic studies revealed that QuR-lipo reversed neurological dysfunction by inhibiting the inflammasome signaling axis. Together, these findings provide an innovative strategy for brain-targeted delivery of natural bioactive compounds to treat neurodegenerative diseases.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114678"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089560","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":"Engineered cargo-free nanoparticle decoys for phagocytic modulation of macrophages","authors":"Peyton M. Panovich ,&nbsp;Aditi Ganesan ,&nbsp;Arianna I. Markey ,&nbsp;Miriam E. Stevens ,&nbsp;Owen M. Kelly ,&nbsp;Alexandra S. Piotrowski-Daspit","doi":"10.1016/j.jconrel.2026.114699","DOIUrl":"10.1016/j.jconrel.2026.114699","url":null,"abstract":"<div><div>Polymeric nanoparticles (NPs) are a versatile delivery platform for non-viral genetic therapies. However, a key shortcoming of polymeric NPs (and other non-viral delivery vehicles) is the often-high accumulation of NPs within the liver and the spleen after systemic intravenous (IV) administration <em>in vivo</em>. This phenomenon is largely the result of the mononuclear phagocytic system (MPS), a class of phagocytic cells responsible for native immune response and toxin clearance within the body. One strategy to overcome NP clearance by the MPS is the use of phagocytic modulating pre-treatments to intentionally and temporarily alter the phagocytic behavior of macrophages such that sequentially administered therapeutic NPs can be delivered to extrahepatic and extrasplenic tissues. Here, we explore the use cargo-free poly(lactic-<em>co</em>-glycolic acid) (PLGA) “decoy” NPs as pre-treatments for phagocytic evasion of sequentially administered therapeutic NPs. Analysis via flow cytometry and fluorescence microscopy reveal that cargo-free PLGA NPs significantly decrease uptake of subsequently administered therapeutic NPs by macrophages. Specifically, we conclude that variables such as size, surfactant composition, and timing of pre-treatment influence the behavior of cargo-free PLGA decoy NPs in modulating phagocytic activity of macrophages. In <em>in vivo</em> studies, we report decreased accumulation in the liver and increased deposition of therapeutic NPs in the lung with pre-administration of cargo-free decoy PLGA NPs. Together, these studies suggest pre-treatment with decoy NPs can reduce therapeutic NP clearance, with the potential to improve nanomedicine delivery capabilities for a wide range of therapeutics and disease targets.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114699"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146642","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":"pH-responsive polymeric-peptide complex enhances tumor immunogenic cell death by membrane disruption","authors":"Guanyu Jin ,&nbsp;Zhaofan Yang ,&nbsp;Lanqing Wang ,&nbsp;Shucheng Zhang ,&nbsp;Shanyi Lin ,&nbsp;Zhuoling Bi ,&nbsp;Bingzheng Yu ,&nbsp;Yuanzhen Su ,&nbsp;Sijun Xiang ,&nbsp;Irina A. Veselova ,&nbsp;Hao Liu ,&nbsp;Fangda Li ,&nbsp;Shuilin Wu ,&nbsp;Mingqiang Li ,&nbsp;Xuesi Chen ,&nbsp;Shixian Lv","doi":"10.1016/j.jconrel.2026.114660","DOIUrl":"10.1016/j.jconrel.2026.114660","url":null,"abstract":"<div><div>Melittin, the principal bioactive component of bee venom, exhibits potent anticancer activity. However, its clinical application is hindered by nonspecific hemolytic toxicity. In this study, we developed a pH-responsive polymeric-peptide complex (PCM) to improve anti-tumor activity of melittin while minimizing off-target effects. PCM remained structurally stable under physiological conditions (pH 7.4) but underwent rapid disassembly in the mildly acidic tumor microenvironment (pH 6.8) to expose melittin. The exposed melittin bound to tumor cell membranes, compromised membrane integrity through transmembrane pore formation, leading to tumor cell death. This membrane disruption elicited the release of damage-associated molecular patterns, thereby activating antitumor immune responses. In a murine breast cancer model, low dose administration of PCM significantly inhibited tumor recurrence and metastasis, and generated durable antitumor immunological memory without significant side effects. The mechanistic actions and morphological effects of PCM on tumor cells were thoroughly investigated, providing important theoretical insights for the clinical translation of anticancer peptides.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114660"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048496","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-amplifying pyroptosis nanoinducers enhance cancer immunotherapy through inflammasome priming and activation","authors":"Wenyu Zhang ,&nbsp;Changshun Huang ,&nbsp;Chengzhilin Li ,&nbsp;Xinyu Wang ,&nbsp;Ying Qu ,&nbsp;Wenlong Duan ,&nbsp;Yingyu Hou ,&nbsp;Yingchun Zhao ,&nbsp;Qingbin He ,&nbsp;Jianwei Jiao ,&nbsp;Zhengwei Liu ,&nbsp;Runxiao Zheng","doi":"10.1016/j.jconrel.2026.114689","DOIUrl":"10.1016/j.jconrel.2026.114689","url":null,"abstract":"<div><div>Pyroptosis, a unique type of inflammatory programmed cell death, has recently been identified as a promising therapeutic target for activating the immune system. Nevertheless, the effectiveness of pyroptosis in tumor immunotherapy is impeded by critical factors such as the failure to address nuclear factor-κB (NF-κB) priming, insufficient inflammasome activation, and limited light and oxygen penetration. To confront these challenges, we constructed crystalline dendritic mesoporous gadolinium oxide (DM-Gd₂O₃ nanoparticles) loaded with a peroxyoxalate-based chemiluminescence system and encapsulated by calcium carbonate (CaCO₃) nanoparticles to form self-amplifying pyroptosis nanoinducers. Within the tumor microenvironment (TME), the release of pH-responsive calcium (Ca²⁺) and gadolinium ions (Gd³⁺) promotes the priming of NF-κB and disrupts lysosomal membrane phosphate groups, thereby inducing lysosomal rupture. Additionally, bis(3,4,6-trichloro-2-(pentyloxycarbonyl) phenyl) oxalate (CPPO) reacts with hydrogen peroxide (H₂O₂) to form a high-energy intermediate that emits light, exciting chlorin e6 (Ce6) to produce singlet oxygen. This process overcomes the limitations of light penetration and tumor hypoxia, synergizes with pyroptosis, and triggers a strong antitumor immune response <em>in vitro</em> and <em>in vivo</em>. This study introduces a novel approach to the design of self-amplifying pyroptosis nanoinducers for tumor immunotherapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114689"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146134114","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":"Intrapericardial delivery of FAP-CAR-T cells via a ROS-responsive hydrogel to treat cardiac fibrosis","authors":"Bihui Cao ,&nbsp;Manting Liu ,&nbsp;Sainiwaer Anwaier ,&nbsp;Xiang Long ,&nbsp;Ting You ,&nbsp;Zijian He ,&nbsp;Haotao Su ,&nbsp;Xinkui Zhang ,&nbsp;Jiaqi Wang ,&nbsp;Huanlei Huang ,&nbsp;Nanbo Liu ,&nbsp;Yujie Jiang ,&nbsp;Hongmo Xiang ,&nbsp;Yehuda G. Assaraf ,&nbsp;Xiaolan Zhu ,&nbsp;Xuelei Ma ,&nbsp;Qi Zhao ,&nbsp;Ping Zhu ,&nbsp;Lu Wang","doi":"10.1016/j.jconrel.2026.114697","DOIUrl":"10.1016/j.jconrel.2026.114697","url":null,"abstract":"<div><div>Cardiac fibrosis is a key pathological feature of both acute and chronic heart diseases, characterized by abnormal accumulation of extracellular matrix resulting from fibroblast activation. Although fibroblast activation protein (FAP)-targeted chimeric antigen receptor (CAR) T cell therapy has shown promise in selectively eliminating activated fibroblasts, systemic administration remains limited by off-target toxicity and insufficient trafficking to the diseased myocardium. Here, we present a reactive oxygen species (ROS)-responsive hydrogel designed for intrapericardial delivery of FAP-specific CAR-T (FAP-CAR-T) cells to locally treat post-myocardial infarction (MI) fibrosis. This hydrogel, based on a thioketal-crosslinked polyethylene glycol matrix, selectively degrades in the ROS-enriched microenvironment of fibrotic tissue, enabling the controlled release of encapsulated FAP-CAR-T cells. In vitro, FAP-CAR-T cells exhibited antigen-dependent cytotoxicity against FAP⁺ targets, and hydrogel-encapsulated CAR-T cells maintained robust proliferation and showed ROS-triggered release kinetics. Using murine models of MI-induced fibrosis, the hydrogel-based intrapericardial delivery strategy enhanced FAP-CAR-T cells infiltration, persistence, and effector function, resulting in significant depletion of activated fibroblasts, attenuation of fibrotic remodeling, and preservation of cardiac structure and left ventricular function. This hydrogel-based CAR-T immunotherapeutic platform provides a localized, targeted, and on-demand strategy for combating cardiac fibrosis and may offer broader translational potential for the treatment of fibrotic diseases.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114697"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146134054","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":"Delivery science: Its increasing importance for the next generation of medicines","authors":"Marianne Ashford ,&nbsp;Annette Bak","doi":"10.1016/j.jconrel.2026.114663","DOIUrl":"10.1016/j.jconrel.2026.114663","url":null,"abstract":"<div><div>The therapeutic landscape has diversified beyond traditional small molecules to encompass a plethora of different modalities including antibodies, peptides and nucleic acids as well as more complex small molecules. Increasingly heterofunctional molecules, targeted drug conjugates, including antibody drug conjugates, oligonucleotide drug conjugates and radionuclide conjugates, are being used to improve efficacy, reduce side effects and enable lower doses. These diverse modalities present distinct delivery needs. This perspective briefly reflects on the main drug modality classes, their delivery challenges and summarises the current delivery solutions and trends including amorphous solid dispersions, long acting injectables, approaches to high concentration subcutaneous delivery of biologics and lipid nanoparticles for delivery of mRNA. There is a continual drive for more patient centric formulations. We argue that this modality evolution heightens the importance of drug delivery as a core design parameter in discovery rather than as a downstream fix. Across modalities, targeted delivery remains pivotal to improve therapeutic index and to lower dose and environmental footprint. Translational success requires early collaboration among preclinical safety, CMC, clinical, and regulatory teams to define critical quality attributes and develop <em>in vitro/in silico</em> tools for predicting <em>in vivo</em> performance. Delivery science is positioned to play a leading role in enabling the next generation of medicines, accelerating translation, and improving patient outcomes.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114663"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095686","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":"Albofungin vesicle nanobombs trigger lysosomal disruption for self-enhanced pyroptosis and cGAS-STING pathway activation in glioblastoma immunotherapy","authors":"Chen Chen ,&nbsp;Shuai Tan ,&nbsp;Xiaojing Zhu ,&nbsp;Zefeng Song ,&nbsp;Yutong Xing ,&nbsp;Wenrui Jin ,&nbsp;Jingyi Xu ,&nbsp;Siqi Song ,&nbsp;Haoran Geng ,&nbsp;Xingyu Chen ,&nbsp;Chunshuai Huang ,&nbsp;Zhenyong Wu","doi":"10.1016/j.jconrel.2026.114718","DOIUrl":"10.1016/j.jconrel.2026.114718","url":null,"abstract":"<div><div>Glioblastoma (GBM) remains one of the most intractable malignancies owing to the dual challenges of the blood brain barrier (BBB) and profound immunosuppression. Here, we present a nanobomb (OMV-ApoE@ALF) that integrates heterologous production of the aromatic polyketide albofungin (ALF) with programmable outer membrane vesicles (OMVs) displaying ApoE peptides for GBM immunotherapy. OMV-ApoE@ALF efficiently crossed the BBB, accumulated in tumors, and functioned as a lysosomal nanobomb to boost pyroptosis and activate cGAS-STING pathway, thereby promoting dendritic cell maturation, T-cell infiltration, and durable antitumor immunity. Mechanistically, OMV-ApoE@ALF delivered ALF into lysosomes, inducing lysosomal disruption, reactive oxygen species (ROS) production, and subsequent mitochondrial damage. Crucially, this lysosomal rupture also suppressed protective autophagy of tumor cells themselves, thereby reinforcing the cascade activation between caspase-3/GSDME-dependent pyroptosis and cGAS-STING signaling pathway. This lysosomal disruption-nanobomb represents a new strategy for advancing GBM immunotherapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114718"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146122","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}