Journal of Controlled Release最新文献

Brain-targeting biomimetic nanozyme enhances neuroprotection in ischemic stroke by remodeling the neurovascular unit

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-04-18 DOI: 10.1016/j.jconrel.2025.113750

Yan Song, Luyao Wang, Tingting Peng, Lingling Shan, Bo Wan, Mingtan Tang, Yuxia Luan, Yue Jiang, Wenxiu He

{"title":"Brain-targeting biomimetic nanozyme enhances neuroprotection in ischemic stroke by remodeling the neurovascular unit","authors":"Yan Song, Luyao Wang, Tingting Peng, Lingling Shan, Bo Wan, Mingtan Tang, Yuxia Luan, Yue Jiang, Wenxiu He","doi":"10.1016/j.jconrel.2025.113750","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113750","url":null,"abstract":"Dysfunction of the neurovascular unit significantly impacts the prognostic outcomes of ischemic stroke. However, effective strategies to comprehensively modulate the neurovascular unit have yet to be developed. In this work, we introduce a brain-targeting biomimetic nanozyme, A@HPB@THSA, designed to mitigate neurovascular unit dysfunction following ischemia/reperfusion. Specifically, aspirin is encapsulated within hollow Prussian blue nanozyme, which is subsequently modified with brain-targeting T7 peptide-conjugated human serum albumin, ultimately forming the composite A@HPB@THSA. The overexpression of transferrin receptors on cerebral vascular endothelial cells, along with compromised blood-brain barrier (BBB) permeability, facilitates the accumulation of A@HPB@THSA at cerebral ischemic lesions. The hollow Prussian blue nanozyme component effectively scavenges reactive oxygen species in ischemia/reperfusion-affected brain cells. While the aspirin component inhibits platelets aggregation and neutrophils infiltration, thereby preventing microvascular “no-reflow” and preserving the integrity of the BBB. In rat models of transient middle cerebral artery occlusion, A@HPB@THSA demonstrated comprehensive modulation of the neurovascular unit, including reduced BBB permeability, promotion of microglia polarization toward an anti-inflammatory phenotype, and enhanced neuronal survival. This work provides a promising platform to reverse dysfunctional neurovascular unit for ischemic stroke treatment.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"43 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846819","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

Lipid nanoparticles target neutrophils to reduce SARS-CoV-2-induced lung injury and inflammation

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-04-18 DOI: 10.1016/j.jconrel.2025.113736

Ha Eun Shin, Stefanos Giannakopoulos, Joo Dong Park, Hye Jung Jang, Chun Gwon Park, Sean V. Murphy, Juwon Park, Saguna Verma, Wooram Park

{"title":"Lipid nanoparticles target neutrophils to reduce SARS-CoV-2-induced lung injury and inflammation","authors":"Ha Eun Shin, Stefanos Giannakopoulos, Joo Dong Park, Hye Jung Jang, Chun Gwon Park, Sean V. Murphy, Juwon Park, Saguna Verma, Wooram Park","doi":"10.1016/j.jconrel.2025.113736","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113736","url":null,"abstract":"The need to understand key players driving pulmonary inflammation and fibrosis in COVID-19 patients leading to effective preventive strategies is imminent. Excessive neutrophil activation, including extracellular trap (NET) formation, is associated with severe COVID-19 and long-term sequelae. However, the clinical applications of neutrophil-targeting therapies are challenging due to short bioavailability and lack of cell-type specificity. This study presents a lipid nanoparticle (LNP) platform designed to deliver two established NET inhibitors, DNase I and Sivelestat (Siv) referred to as DPNLNPs, specifically to lung neutrophils. In vitro and in vivo experiments demonstrate that DPNLNPs preferentially accumulate in the lung neutrophils and degrade NETs as efficiently as the free DNase I and Siv. Additionally, administration of DPNLNPs in K18-hACE2 mice significantly inhibited SARS-CoV-2-induced NETs at a much lower dose than the free drugs and correlated with reduced lung and systemic inflammation, lung epithelium injury, and collagen deposition. Importantly, DPNLNP treatment only during the symptomatic phase of infection improved SARS-CoV-2 outcome revealing the complex role of NETs in COVID-19 pathogenesis. Together, this study serves as a proof-of-concept for adapting the LNP platform to deliver more than one immunomodulatory drug in a cell-specific manner to manage NET-associated complications in COVID-19 and other respiratory diseases.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"32 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849692","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

If you want to go far, go together

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-04-18 DOI: 10.1016/j.jconrel.2025.113746

Laura M. Ensign

引用次数: 0

Cell membrane nanoparticles in cancer therapy: From basic structure to surface functionalization

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-04-18 DOI: 10.1016/j.jconrel.2025.113752

Munsik Kim, Rohbin Choi, Lian Kim, Yeu-Chun Kim, Ilkoo Noh

{"title":"Cell membrane nanoparticles in cancer therapy: From basic structure to surface functionalization","authors":"Munsik Kim, Rohbin Choi, Lian Kim, Yeu-Chun Kim, Ilkoo Noh","doi":"10.1016/j.jconrel.2025.113752","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113752","url":null,"abstract":"Cell membrane nanoparticles (CNPs) have recently garnered significant attention as effective drug-delivery vehicles. Beyond their simple function of encapsulating cargo within a lipid bilayer structure, the cell membrane is a complex entity derived from biological materials, presenting a variety of surface proteins and glycans. Notable features that enhance their effectiveness as delivery vehicles include the inhibition of protein corona formation in the plasma and the suppression of macrophage phagocytosis, both of which contribute to prolonged blood circulation. Furthermore, CNPs exhibit homotypic targeting effects toward their cells of origin, resulting in reduced side effects, and because they are not xenobiotics, the likelihood of nonspecific immune activation is also minimized. This review focuses on various applications of CNPs in cancer therapeutic studies, examining their structural evolution and surface engineering developments. We introduce studies that leverage the inherent functionality of cell membranes and recent research in functional CNPs synthesized through genetic or chemical engineering methods. Through this review, we aim to trace the progression of CNP research, explore potential directions for their use in biomedical applications, and assess the prospects for clinical trials.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"86 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846820","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

Biomimetic hyaluronic acid-stabilized zinc oxide nanoparticles in acne treatment: A preclinical and clinical approach

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-04-18 DOI: 10.1016/j.jconrel.2025.113754

Jiaojiao Zhu, Tiao Wen, Yunxiao Ma, Qingya Zeng, Pei Li, Wenhu Zhou

{"title":"Biomimetic hyaluronic acid-stabilized zinc oxide nanoparticles in acne treatment: A preclinical and clinical approach","authors":"Jiaojiao Zhu, Tiao Wen, Yunxiao Ma, Qingya Zeng, Pei Li, Wenhu Zhou","doi":"10.1016/j.jconrel.2025.113754","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113754","url":null,"abstract":"Acne vulgaris is a common chronic inflammatory skin condition, often caused by C. acnes infection. While ZnO has shown promise as an antibacterial agent in acne treatment, concerns over toxicity and non-selective bacterial killing remain. In this study we developed a hyaluronic acid-stabilized nano‑zinc oxide (HA-ZnO) formulation aimed at enhancing the therapeutic efficacy and safety of ZnO for acne treatment. HA-ZnO was synthesized through biomimetic mineralization. HA-ZnO targeted acne-prone areas, especially sebaceous glands, without skin penetration. HA-ZnO demonstrated selective antibacterial activity against C. acnes, exhibiting a killing efficacy more than 16 times greater than that against S. epidermidis. The HA coating also improved ZnO's stability in acidic conditions, mitigating potential toxicity and side effects. Additionally, the sustained release of Zn2+ promoted cell proliferation and migration, reducing sebum secretion, and exerting anti-inflammatory effects, supporting scar-free acne repair and preventing recurrence. In preclinical models, HA-ZnO outperformed erythromycin ointment in treating acne, with no toxicity observed in zebrafish and HET-CAM. A clinical trial further confirmed its efficacy in reducing acne lesions and redness, with high safety. These results highlight HA-ZnO as a promising therapeutic strategy for acne, combining potent antibacterial and skin-repairing effects with enhanced safety.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"1 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849691","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

Collagenase-modified polydopamine nanoparticles for safe and effective vitreolysis

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-04-18 DOI: 10.1016/j.jconrel.2025.113753

An-Katrien Minnaert, Van-Phuc Nguyen, Aranit Harizaj, Ilia Goemaere, Bart Van Puyvelde, Maarten Dhaenens, Félix Sauvage, Dieter Deforce, Stefano Salmaso, Paolo Caliceti, Kevin Braeckmans, Karen Peynshaert, Yannis M. Paulus, Stefaan C. De Smedt, Katrien Remaut

{"title":"Collagenase-modified polydopamine nanoparticles for safe and effective vitreolysis","authors":"An-Katrien Minnaert, Van-Phuc Nguyen, Aranit Harizaj, Ilia Goemaere, Bart Van Puyvelde, Maarten Dhaenens, Félix Sauvage, Dieter Deforce, Stefano Salmaso, Paolo Caliceti, Kevin Braeckmans, Karen Peynshaert, Yannis M. Paulus, Stefaan C. De Smedt, Katrien Remaut","doi":"10.1016/j.jconrel.2025.113753","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113753","url":null,"abstract":"Anomalous posterior vitreous detachment (aPVD) is involved in the pathogenesis of many vitreoretinal disorders. This condition is currently managed by vitrectomy, a routine but invasive surgery which is especially challenging in patients with firm vitreoretinal adhesions. Since 1998, pharmacological vitreolysis emerged as a potential replacement or adjunct therapy to vitrectomy. Over the years, most attention was focused on enzymes, but their use has been limited mainly due to retinal toxicity. To revive the potential of enzymatic vitreolysis, we aimed to immobilize collagenase on the surface of polydopamine nanoparticles to prevent penetration into the retinal layers. We synthesized stable and functional collagenase-modified nanoparticles and were able to induce vitreous liquefaction and complete PVD ex vivo. Moreover, we demonstrated a substantial reduction in retinal toxicity upon injection in bovine vitreoretinal explants. Subsequent in vivo analysis revealed that retinal morphology and function were preserved, in contrast to free collagenase. Despite the presence of vitreous hemorrhages, which can possibly be avoided by optimization of the experimental set-up, we believe to have given the first step in the right direction towards nanotechnology-based enzymatic vitreolysis and to have opened doors for future research.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"10 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849693","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

Stimuli-responsive hydrogel with spatiotemporal co-delivery of FGF21 and H₂S for synergistic diabetic wound repair

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-04-17 DOI: 10.1016/j.jconrel.2025.113749

Liuxi Chu, Jia-Men Shen, Zeping Xu, Junqing Huang, Luying Ning, Zunyong Feng, Yi Jiang, Ping Wu, Chen Gao, Wenjia Wang, Ziyi Li, Shaoxia Ning, Xinwang Ying, Shiyao Chen, Piao Wang, Xujie Zhou, Qian Xu, Ao Fang, Quan Zhang, Yuetong Wang, Zhou-Guang Wang

{"title":"Stimuli-responsive hydrogel with spatiotemporal co-delivery of FGF21 and H₂S for synergistic diabetic wound repair","authors":"Liuxi Chu, Jia-Men Shen, Zeping Xu, Junqing Huang, Luying Ning, Zunyong Feng, Yi Jiang, Ping Wu, Chen Gao, Wenjia Wang, Ziyi Li, Shaoxia Ning, Xinwang Ying, Shiyao Chen, Piao Wang, Xujie Zhou, Qian Xu, Ao Fang, Quan Zhang, Yuetong Wang, Zhou-Guang Wang","doi":"10.1016/j.jconrel.2025.113749","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113749","url":null,"abstract":"Chronic diabetic wounds pose significant clinical challenges due to persistent inflammation, impaired angiogenesis, and disrupted cellular homeostasis. To address these multifactorial barriers, we engineered an injectable, biodegradable, and biocompatible methylated silk fibroin (SilMA) hydrogel system co-loaded with cobalt sulfide (CoS) and fibroblast growth factor 21 (FGF21), designed for on-demand therapeutic release. In the acidic microenvironment characteristic of the inflammatory phase of diabetic wounds, the hydrogel rapidly releases hydrogen sulfide (H₂S) and Co2+ ions, mitigating inflammation and exerting antibacterial effects. Subsequently, during the proliferative and remodeling phases, sustained release of FGF21 promotes cellular proliferation, angiogenesis, and enzymatic homeostasis, thereby accelerating wound healing. Mechanistic studies reveal that the hydrogel facilitates M2 macrophage polarization and activates the JAK/STAT signaling pathway, leading to upregulation of vascular endothelial growth factor (VEGF). Additionally, it enhances antioxidant enzyme activities (superoxide dismutase, catalase, glutathione) while suppressing pro-oxidant enzymes (NADPH oxidase, lipoxygenase, cyclooxygenase). In vivo studies using a diabetic mouse model demonstrate that this dual-functional hydrogel significantly improves wound closure rates and tissue regeneration. These findings suggest that the SilMA-FGF21/CoS hydrogel represents a promising therapeutic strategy for the management of diabetic wounds.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"38 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846946","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

Reversing hypoxia-induced immune evasion in tumors to enhance cancer immunotherapy

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-04-17 DOI: 10.1016/j.jconrel.2025.113745

Qiuting Sun, Guisong Shan, Wanrong Wang, Xueqian Li, Laiqing Yan, Rui Peng, Mengyu Liu, Xulin Huang, Xiaohe Ren, Xiaoyan He, Lei Qiao

{"title":"Reversing hypoxia-induced immune evasion in tumors to enhance cancer immunotherapy","authors":"Qiuting Sun, Guisong Shan, Wanrong Wang, Xueqian Li, Laiqing Yan, Rui Peng, Mengyu Liu, Xulin Huang, Xiaohe Ren, Xiaoyan He, Lei Qiao","doi":"10.1016/j.jconrel.2025.113745","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113745","url":null,"abstract":"The strategy of inducing tumors to release damage-associated molecular patterns (DAMPs) to trigger immunogenic cell death has garnered significant attention in cancer therapy. However, the hypoxic tumor microenvironment, which is often programmed by cancer cells, results in the release of immunosuppressive DAMPs (iDAMPs), which substantially influence antitumor immune responses. In this study, we developed a redox-responsive carboxymethyl chitosan (CMC)-based nanoplatform for the sequential delivery of a hypoxia-inducible factor 1-α (HIF-1α) inhibitor, 3-(5′-hydroxymethyl-2-furyl)-1-benzylindazole (YC-1), and the chemotherapeutic agent doxorubicin (DOX), aimed to restore therapeutic sensitization and immunostimulation in tumors. The preferential release of YC-1 effectively targets the HIF-1α/cyclooxygenase-2 (COX-2) axis, significantly reducing the secretion of immunosuppressive factor prostaglandin E2 (PGE2), thereby resensitizing tumors to T cell-mediated immunity. Additionally, YC-1 mitigates hypoxia-induced tumor chemoresistance by inhibiting the HIF-1α/P-glycoprotein (P-gp) axis, further improving the immunotherapeutic efficacy of DOX. Our work demonstrates that regulating hypoxia-induced immunosuppressive factors in tumors contributes to the inhibition of both primary and metastatic tumors, offering a promising approach to enhance immunotherapies.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"4 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841099","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

Gentle and efficient engineering of primary human NK cells by photoporation with polydopamine nanosensitizers

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-04-17 DOI: 10.1016/j.jconrel.2025.113742

C. Hinnekens , J. Ramon , M. Birben , W.T.V. Germeraad , A. Harizaj , M. De Velder , S.C. De Smedt , B. Vandekerckhove , K. Braeckmans , J.C. Fraire

{"title":"Gentle and efficient engineering of primary human NK cells by photoporation with polydopamine nanosensitizers","authors":"C. Hinnekens , J. Ramon , M. Birben , W.T.V. Germeraad , A. Harizaj , M. De Velder , S.C. De Smedt , B. Vandekerckhove , K. Braeckmans , J.C. Fraire","doi":"10.1016/j.jconrel.2025.113742","DOIUrl":"10.1016/j.jconrel.2025.113742","url":null,"abstract":"<div><div>Over the past several years, adoptive T cell therapies have accounted for great success in treating diverse malignancies. More recently, however, NK cells are being investigated as a promising alternative. Due to the innate antiviral properties of NK cells, viral engineering has proven to be challenging, prompting the development of non-viral transfection technologies. In this work, we evaluated photoporation with polydopamine nanosensitizers as a notable upcoming transfection technology for the engineering of NK cells and compared its performance to Nucleofection. Our results demonstrated the successful transfection of NK cells with eGFP mRNA and gene editing with Cas9 ribonucleoproteins (RNPs) for knock-out of the KLRC1 gene, encoding for the inhibitory NK cell receptor NKG2A. Importantly, no alterations to the phenotype of the cells (e.g. expression of surface markers and release of cytokines) could be detected, nor was the proliferation or cytolytic capacity of the cells influenced by either of the treatments. Overall, our findings highlight the potential of polydopamine-sensitized photoporation as a gentle and efficient transfection technology for NK cell engineering.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113742"},"PeriodicalIF":10.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841100","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 “Dual-responsive nanoparticles for enhanced drug delivery in breast cancer chemotherapy” [Volume 377, 10 January 2025, Pages 146–161]

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-04-17 DOI: 10.1016/j.jconrel.2025.113724

Yuxin Ren , Peishan Li , Ying Xie , Jiarui Xu , Qian Luo , Ming Chen , Rui Liu , Hexuan Feng , Yuling Chen , Yixuan Liu , Chunjie Bao , Jialun Duan , Jianwei Li , Wanliang Lu

引用次数: 0