Journal of Controlled Release最新文献_第8页

Oral multifunctional gel beads for the targeted treatment of inflammatory bowel disease 靶向治疗炎症性肠病的口服多功能凝胶珠

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-17 DOI: 10.1016/j.jconrel.2025.114240

Danlei Hu , Dongmei Chen , Aoxue Zhang , Kuiyu Meng , Min Chen , Mubbashar Abbas , Wei Qu , Shuyu Xie

{"title":"Oral multifunctional gel beads for the targeted treatment of inflammatory bowel disease","authors":"Danlei Hu , Dongmei Chen , Aoxue Zhang , Kuiyu Meng , Min Chen , Mubbashar Abbas , Wei Qu , Shuyu Xie","doi":"10.1016/j.jconrel.2025.114240","DOIUrl":"10.1016/j.jconrel.2025.114240","url":null,"abstract":"<div><div>Current IBD therapies face limitations such as systemic toxicity, off-target effects, and microbiota dysbiosis. We developed an oral multifunctional gel bead integrating three innovations: (1) a butyrate–apigenin synergy that inhibits NF-κB via CK2/p65 phosphorylation suppression, activates a PPAR-γ-mediated metabolic shift to β-oxidation, and modulates the microbiota by enhancing Bacteroidetes/suppressing Enterobacteriaceae; (2) an apigenin–butyrate ester prodrug overcoming organoleptic issues while enabling CK2 targeting; and (3) a pH/enzyme–responsive delivery system using the FDA-approved ascorbyl palmitate/alginate, achieving gastric protection, charge–mediated colitis targeting, and esterase–triggered release. In colitis model mice, gel beads restore clinical parameters, intestinal integrity, and microbial balance, outperforming apigenin-butyrate ester and 5-ASA at half-doses with extended intervals. It significantly downregulated colon CK2 expression (4.07-fold) and the phospho-P65/total P65 ratio (3.04-fold). This integrated strategy combining multimodal drug actions and precision delivery establishes a new paradigm for efficient and alternative IBD therapeutics with reduced dosing requirements.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114240"},"PeriodicalIF":11.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145072145","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

Mitochondria-targeted hybrid nanovesicles trigger immunogenic cell death and remodel tumor neutrophils for enhanced colorectal cancer immunotherapy 线粒体靶向杂交纳米囊泡触发免疫原性细胞死亡并重塑肿瘤中性粒细胞，增强结直肠癌免疫治疗

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-17 DOI: 10.1016/j.jconrel.2025.114242

Hongxin Tan , Na Li , Sicheng Shu , Ziyan Fan , Jie Deng , Jingjing Wu , Xu Zhou , Qi Huang , Xi Cao

{"title":"Mitochondria-targeted hybrid nanovesicles trigger immunogenic cell death and remodel tumor neutrophils for enhanced colorectal cancer immunotherapy","authors":"Hongxin Tan , Na Li , Sicheng Shu , Ziyan Fan , Jie Deng , Jingjing Wu , Xu Zhou , Qi Huang , Xi Cao","doi":"10.1016/j.jconrel.2025.114242","DOIUrl":"10.1016/j.jconrel.2025.114242","url":null,"abstract":"<div><div>Cancer immunotherapy has garnered significant attention for its ability to reinstate immune responses to eliminate cancer effectively. Among immune cells, neutrophils play a dual-edged sword role in cancer, and the selective activation of beneficial neutrophil populations and targeted inhibition of tumor-promoting neutrophils have shown significant potential in cancer therapy. Here, we developed a neutrophil mimic nanovehicle (Neutrosome) capable of targeting colorectal cancer mitochondria (MNeutrosome), which consists of active neutrophil membranes hybridized with mitochondria-targeting liposome loaded with β-Lapachone (Liposome@Lapa), which is proposed to induce immunogenic cell death (ICD) and modulate the immune microenvironment. Our findings demonstrate that MNeutrosome@Lapa selectively accumulates in colorectal cancer mitochondria and activates quinone oxidoreductase-1 (NQO1), leading to robust reactive oxygen species (ROS) production and subsequent cancer cell apoptosis. Notably, the unloaded MNeutrosome was shown to reduce neutrophil infiltration into tumor tissue, whereas MNeutrosome@Lapa reprogrammed tumor-associated neutrophils (TANs) from a pro-tumor N2 phenotype to an anti-tumor N1 phenotype, further contributing to immune modulation. Overall, MNeutrosome@Lapa demonstrated excellent biocompatibility and significant therapeutic efficacy and represents a promising therapeutic platform for CRC treatment.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114242"},"PeriodicalIF":11.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077351","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

Safety and efficacy of KRAS antisense oligonucleotides and RIG-I agonists delivered by extracellular vesicles for pancreatic cancer peritoneal metastasis treatment 细胞外囊泡递送KRAS反义寡核苷酸和rig - 1激动剂治疗胰腺癌腹膜转移的安全性和有效性

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-16 DOI: 10.1016/j.jconrel.2025.114239

Tram T.T. Nguyen , Xuan T.T. Dang , Cao Dai Phung , Lan Thi Ngoc Tran , Nguyen Trong Phuoc Do , Eric Y.M. Yeo , Nhut Minh Tran , Brendon Zhi Jie Yeo , Celest P. Lixuan , Nhung T.H. Nguyen , Hung Xuan Nguyen , Huong Thu Ngo , Glenn K. Bonney , Dahai Luo , Minh T.N. Le

{"title":"Safety and efficacy of KRAS antisense oligonucleotides and RIG-I agonists delivered by extracellular vesicles for pancreatic cancer peritoneal metastasis treatment","authors":"Tram T.T. Nguyen , Xuan T.T. Dang , Cao Dai Phung , Lan Thi Ngoc Tran , Nguyen Trong Phuoc Do , Eric Y.M. Yeo , Nhut Minh Tran , Brendon Zhi Jie Yeo , Celest P. Lixuan , Nhung T.H. Nguyen , Hung Xuan Nguyen , Huong Thu Ngo , Glenn K. Bonney , Dahai Luo , Minh T.N. Le","doi":"10.1016/j.jconrel.2025.114239","DOIUrl":"10.1016/j.jconrel.2025.114239","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) often metastasizes to the peritoneum and is highly resistant to treatments due to its immunosuppressive microenvironment. In this study, we evaluate the safety and efficacy of a novel therapeutic strategy that combines KRAS-targeting antisense oligonucleotides (ASOs) with immunomodulatory RNA (immRNA), a RIG-I agonist, both delivered by extracellular vesicles (EVs), in preclinical models using PDAC patient-derived organoids and mice bearing PDAC peritoneal metastasis. Our data demonstrate that the combination of <em>KRAS</em> ASO and immRNA synergistically activates anti-tumor immune responses. EV-mediated co-delivery of both agents significantly inhibits tumor growth, reduces peritoneal metastasis, and markedly prolongs overall survival through the induction of immunologic cancer cell death. Importantly, this combination therapy is well-tolerated in non-human primates, with no observable changes in physical condition or behavior, blood parameters, or organ histology. These findings suggest that EV-delivered <em>KRAS</em> ASO and immRNA is a safe and potent therapeutic approach for treating PDAC and its peritoneal metastasis, positioning it as a promising strategy for future clinical advancement.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114239"},"PeriodicalIF":11.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068052","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 “Metal-phenolic epigallocatechin gallate‑zinc antioxidant nanoparticles for cataract treatment” [Journal of Controlled Release 383 (2025) 113798] “用于白内障治疗的金属酚类表没食子儿茶素没食子酸盐锌抗氧化纳米颗粒”的勘误表[Journal of Controlled Release 383 (2025) 113798]

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-15 DOI: 10.1016/j.jconrel.2025.114216

Jiahao Wang, Renjie Zhang, Hongying Xie, Yuexin Yang, Hao Chen, Quankui Lin

引用次数: 0

SitoC7A-modified lipid nanoparticles for integrated mRNA delivery and targeted STING activation sitoc7a修饰的脂质纳米颗粒用于整合mRNA传递和靶向STING激活

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-15 DOI: 10.1016/j.jconrel.2025.114238

Lijie Qiao , Na Fan , Yupei Zhang , Yuting Chen , Shugang Qin , Xiangrong Song

{"title":"SitoC7A-modified lipid nanoparticles for integrated mRNA delivery and targeted STING activation","authors":"Lijie Qiao , Na Fan , Yupei Zhang , Yuting Chen , Shugang Qin , Xiangrong Song","doi":"10.1016/j.jconrel.2025.114238","DOIUrl":"10.1016/j.jconrel.2025.114238","url":null,"abstract":"<div><div>Messenger RNA (mRNA) vaccine efficacy requires delivery systems that maximize antigen expression while precisely modulating innate immune activation. However, many conventional adjuvants induce type I interferons that inadvertently suppress mRNA translation, compromising vaccine efficacy. To overcome this limitation, we engineered a multifunctional lipid nanoparticle (LNP) by partially substituting a fraction of the structural lipid cholesterol with SitoC7A - a conjugate of sitosterol and the STING (Stimulator of Interferon Genes) agonist (C7A) linked via a reducible disulfide bond. This single SitoC7A component serves dual roles: its disulfide bond markedly enhances LNP uptake by dendritic cells (DCs) and boosts mRNA translation, while its C7A moiety selectively triggers STING signaling within DCs, avoiding systemic interferon responses. This integrated design yielded robust DC maturation and superior antigen presentation. In murine models, SitoC7A-LNPs encapsulating SARS-CoV-2 mRNA elicited potent protective immunity, while tumor antigen-loaded LNPs significantly suppressed lymphoma progression. We introduce a principle for the novel LNP design wherein a single engineered lipid simultaneously provides structural support, enhances mRNA delivery and expression specifically in key immune cells, and delivers spatially controlled adjuvanticity creating a versatile and potent platform for next-generation mRNA vaccines.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114238"},"PeriodicalIF":11.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068092","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

Bilayer nanofiber-coated stent integrating internal radiation and spatiotemporal IL-12 release promotes antitumor immune response 结合内辐射和时空释放IL-12的双层纳米纤维涂层支架促进抗肿瘤免疫反应

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-15 DOI: 10.1016/j.jconrel.2025.114231

Juan Qin , Liang-Wei Si , Yi-Ming Liu , Xin-Xin Huang , Rui-Jie Du , Fei Xiong , Duo Wang , Hai-Dong Zhu

{"title":"Bilayer nanofiber-coated stent integrating internal radiation and spatiotemporal IL-12 release promotes antitumor immune response","authors":"Juan Qin , Liang-Wei Si , Yi-Ming Liu , Xin-Xin Huang , Rui-Jie Du , Fei Xiong , Duo Wang , Hai-Dong Zhu","doi":"10.1016/j.jconrel.2025.114231","DOIUrl":"10.1016/j.jconrel.2025.114231","url":null,"abstract":"<div><div>Internal radiation (IR), utilizing iodine-125 (<sup>125</sup>I) seeds as a radiation source, is a clinically established modality for targeted treatment of malignant tumors. In addition to inducing DNA damage in tumor cells, IR therapy can trigger systemic antitumor immune responses, known as the abscopal effect, through immunogenic cell death (ICD). However, the gradual decline in radioactive output and the inherently limited immunogenicity of IR therapy compromise its overall efficacy, with the abscopal effect rarely observed in clinical settings. To overcome these challenges, we developed a bilayer nanofiber-coated stent integrating <sup>125</sup>I seed-based brachytherapy with sustained, spatiotemporally controlled delivery of interleukin-12 (IL-12). Utilizing FDA-approved PLGA and PEO polymers, the inner layer was engineered for IL-12 loading, while the outer layer acted as a regulatory barrier, achieving a biphasic release profile with sustained cytokine delivery for up to 14 days. In vivo studies demonstrated that the IL-12@IRS (IL-12-loaded <sup>125</sup>I internal radiation stent) effectively enhanced antigen presentation and elicited a tumor in situ vaccination effect, thereby promoting durable local and systemic antitumor immunity. This immuno-radiotherapeutic platform not only improves local tumor control but also offers a promising strategy for overcoming immune resistance and inducing robust systemic antitumor effects.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114231"},"PeriodicalIF":11.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059285","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

Tumor microenvironment-responsive metal-natural polyphenol nanozyme for radiosensitization by interfering glucose metabolism and redox homeostasis 肿瘤微环境响应金属-天然多酚纳米酶通过干扰葡萄糖代谢和氧化还原稳态实现放射增敏

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-09-14 DOI: 10.1016/j.jconrel.2025.114219

Jiongyu Ren, Qiang Wen, Shiye Du, Xiaoguang Ge, Lu Li, Lan Wei, Shi Gao

{"title":"Tumor microenvironment-responsive metal-natural polyphenol nanozyme for radiosensitization by interfering glucose metabolism and redox homeostasis","authors":"Jiongyu Ren, Qiang Wen, Shiye Du, Xiaoguang Ge, Lu Li, Lan Wei, Shi Gao","doi":"10.1016/j.jconrel.2025.114219","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.114219","url":null,"abstract":"Radiotherapy (RT) still faces great challenges with tumor hypoxia, antioxidant mechanisms and high glucose metabolism. Herein, we report a tumor microenvironment (TME)-responsive ruthenium-natural polyphenol phloretin (RPP) nanozyme with glucose oxidase (GOx), catalase (CAT), peroxidase (POD) and glutathione peroxidase (GPX) -like activities, which serves as an efficient and safe radiosensitizer for enhanced RT. Under an acidic TME, RPP nanozyme aerobically consumes the intracellular glucose and reduces the production of lactic acid, and meanwhile, the <em>in-situ</em> exposure of phloretin can block the uptake of extracellular glucose by inhibiting glucose transporters, making it more efficient to inhibit glycolysis and minimize oxygen consumption. Moreover, RPP nanozyme can not only rapidly catalyze hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) into reactive oxygen species (ROS) and oxygen to alleviate tumor hypoxia, but also down-regulate the intracellular glutathione (GSH) and lactic acid level to overcome antioxidant metabolism. Both <em>in vitro</em> and <em>in vivo</em> studies manifest that RPP nanozyme significantly enhance the radiosensitivity of 4 T1 tumor cells. Besides, <em>in vivo</em> positron emission tomography imaging, utilizing clinical imaging agents, validates the decreased glucose uptake and hypoxia relief treated by RPP nanozyme. The facile RPP nanozyme with the regulating ability of TME can achieve TME-responsive radiosensitization, providing promising potential for tumor therapy.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"311 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056879","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

Outside Back Cover 外封底

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-13 DOI: 10.1016/S0168-3659(25)00826-0

引用次数: 0

Antisense oligonucleotide-loaded nanozyme reverses tumor immune suppression through sonogenetic metabolic therapy 反义寡核苷酸负载纳米酶通过声源代谢疗法逆转肿瘤免疫抑制

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-13 DOI: 10.1016/j.jconrel.2025.114236

Bing Xiong , Jifeng Yu , Congjian Wen , Shaoyue Li , Shen Zhang , Yan Fang , Yingkun Cao , Xin Guan , Yuting Shen , Mingrui Zhu , Xiao Li , Yuli Zhu , Lehang Guo , Huixiong Xu , Haohao Yin

{"title":"Antisense oligonucleotide-loaded nanozyme reverses tumor immune suppression through sonogenetic metabolic therapy","authors":"Bing Xiong , Jifeng Yu , Congjian Wen , Shaoyue Li , Shen Zhang , Yan Fang , Yingkun Cao , Xin Guan , Yuting Shen , Mingrui Zhu , Xiao Li , Yuli Zhu , Lehang Guo , Huixiong Xu , Haohao Yin","doi":"10.1016/j.jconrel.2025.114236","DOIUrl":"10.1016/j.jconrel.2025.114236","url":null,"abstract":"<div><div>The immunosuppressive adenosine generated during immunogenic cell death (ICD) attenuates the ICD-elicited antitumor immune responses, while hypoxia-induced overexpression of CD73 in solid tumors exacerbates adenosine accumulation. Herein, a pioneering sonogenetic metabolic therapy was developed to activate ICD while inhibiting adenosine production. Specifically, a metal-organic framework (MOF) incorporating Ru single-atom catalytic sites was engineered to achieve high-affinity sonosensitizer loading, which was further functionalized with mPEG-<em>d</em>-PEI for efficient delivery of antisense oligonucleotides (ASOs) targeting CD73 mRNA. The designed system exhibited three-tiered therapeutic amplification: Ru-based catalytic sites facilitated atom-economic conversion of tumor-overproduced H₂O₂ into oxygen, alleviating tumor hypoxia. Sustained oxygen supply amplified sonodynamic effect by generating robust ROS to induce tumor apoptosis and ICD, while concurrently suppressing HIF-1α-driven CD73 upregulation. Ultrasound-responsive lysosomal disruption combined with PEI-mediated interference enabled effective lysosomal escape of ASOs, downregulating CD73 expression to inhibit adenosine production. Through immune-metabolic reprogramming of the tumor microenvironment, the approach significantly inhibited tumor growth while establishing long-term immune memory to combat pulmonary metastases in mice. Notably, beyond serving as an antitumor strategy, the developed oligonucleotide delivery system remodels metabolic homeostasis by targeting key components in signaling pathways, thereby providing new perspectives for oligonucleotide-based therapies in metabolic disease treatment.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114236"},"PeriodicalIF":11.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043232","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

Content list including Graphcal Abstracts 内容列表包括图形摘要

IF 11.5 1区医学

Journal of Controlled Release Pub Date : 2025-09-13 DOI: 10.1016/S0168-3659(25)00824-7

引用次数: 0