Journal of Controlled Release最新文献

{"title":"An mRNA vaccine encoding proteasome-targeted antigen enhances CD8+ T cell immunity","authors":"Jin Ling ,&nbsp;Hongwei Chen ,&nbsp;Mengwen Huang ,&nbsp;Jun Wang ,&nbsp;Xiaojiao Du","doi":"10.1016/j.jconrel.2025.02.074","DOIUrl":"10.1016/j.jconrel.2025.02.074","url":null,"abstract":"<div><div>The efficient induction of antigen-specific CD8⁺ T cell activation is crucial in the development of mRNA tumor vaccines. Endogenous antigens are primarily degraded through the ubiquitin-proteasome system, followed by antigen presentation via major histocompatibility complex class I (MHC-I) molecules, leading to the activation of CD8⁺ T cells. Therefore, in this study, a novel mRNA vaccine was developed by fusing the mRNA sequence encoding the antigen with a proteasome-targeting peptide (PTP), aiming to enhance proteasomal targeting of the antigen and facilitate its degradation through the ubiquitin-proteasome system, thereby inducing a stronger CD8⁺ T cell immune response. This study confirmed a significant increase in antigen expression of the antigen-PTP fused mRNA vaccine upon treatment with a VHL inhibitor, as well as notable upregulation of genes associated with the MHC-I antigen-presenting pathway following treatment with the antigen-PTP fused mRNA vaccine. The intramuscular administration of the antigen-PTP fused mRNA vaccine significantly promoted the activation of dendritic cells, macrophages, and T cells in draining lymph nodes and spleens. Additionally, in TC-1 tumor-bearing mice, it markedly suppressed tumor growth, facilitated infiltration of intratumoral antigen-specific CD8⁺ T cells, and induced immune memory.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113578"},"PeriodicalIF":10.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495752","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":"Dendritic cell-based microrobots for enhanced systemic antigen-specific immune tolerance","authors":"Hanfeng Qin ,&nbsp;Junbin Gao ,&nbsp;Wenxin Xu ,&nbsp;Yanzhen Song ,&nbsp;Ruotian Zhang ,&nbsp;Hong Wang ,&nbsp;Yicheng Ye ,&nbsp;Jia Sun ,&nbsp;Jiamiao Jiang ,&nbsp;Haiying Liang ,&nbsp;Ning Zhong ,&nbsp;Hao Tian ,&nbsp;Xiaodong Chen ,&nbsp;Fei Peng ,&nbsp;Yingfeng Tu","doi":"10.1016/j.jconrel.2025.02.062","DOIUrl":"10.1016/j.jconrel.2025.02.062","url":null,"abstract":"<div><div>Current immunotherapeutic approaches for autoimmune disorders primarily rely on the use of generalized immunosuppressive medications. However, most immune drugs and tolerogenic immunomodulators are insufficient on their own to establish antigen-specific immunological tolerance (ASIT). Therefore, steering antigen-presenting cells (APCs) towards a tolerogenic state with minimal risk of broad immune suppression may be an effective approach. In pursuit of enhanced ASIT, magnetic nanoparticles cloaked with an erythrocyte membrane anchored with the model antigen ovalbumin have been successfully developed, allowing for the in vivo conversion of APCs into tolerogenic microrobots that respond to magnetic activation. Actuated by a rotating magnetic field (RMF), the in situ-formed cell-based microrobots can be guided to inflammatory sites, thereby augmenting systemic and local immune tolerance. These tolerogenic microrobots represent an innovative platform for active immunomodulation and provide precise control over the magnitude and direction of immune responses. This breakthrough offers new insights into the therapeutic management of allergies, autoimmune disorders, and the prevention of anti-drug antibodies in biologic therapies.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113566"},"PeriodicalIF":10.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485521","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":"Breaking barriers: Nitric oxide-releasing nanocomplexes for collagen degradation and enhanced αPD-L1 immunotherapy in deep tumor","authors":"Jihye Lee ,&nbsp;Hyoeun Cho ,&nbsp;Jieun Kim,&nbsp;Junha Lim,&nbsp;Yeoul Kang,&nbsp;Won Jong Kim","doi":"10.1016/j.jconrel.2025.02.072","DOIUrl":"10.1016/j.jconrel.2025.02.072","url":null,"abstract":"<div><div>Overcoming the physical barrier of the extracellular matrix (ECM) surrounding tumors is a critical challenge in achieving effective immune checkpoint blockade (ICB). The dense ECM impedes the infiltration of immune checkpoint inhibitors (ICIs) and cytotoxic T lymphocytes (CTLs) into tumor tissues. To address this, we design a nanocomplex incorporating a reactive oxygen species (ROS)-responsive nitric oxide (NO) prodrug around TANNylated αPD-L1. Within the tumor microenvironment (TME), this nanocomplex accumulates and selectively releases NO in response to ROS. The released NO activates matrix metalloproteinases (MMPs) in the ECM, leading to collagen degradation. Following this, the pH-responsive release of αPD-L1 in the deeper tumor regions ensures effective delivery, allowing CTLs to penetrate the tumor more efficiently by bypassing the ECM barrier, thereby enhancing immunotherapy. Overall, this study applies a nanocomplex capable of releasing NO and αPD-L1 in the tumor to a solid tumor model, successfully inhibiting tumor growth by altering the immunosuppressive environment through improved penetration.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113576"},"PeriodicalIF":10.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485516","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":"An industry perspective on hyaluronidase co-formulated biopharmaceutics","authors":"Jeremy Guo,&nbsp;Jingwen Weng,&nbsp;Fangyuan Zhou,&nbsp;Xuejun Gu","doi":"10.1016/j.jconrel.2025.02.069","DOIUrl":"10.1016/j.jconrel.2025.02.069","url":null,"abstract":"<div><div>To deliver biopharmaceutics, subcutaneous (SC) route surpasses intravenous (IV) route unequivocally in time and cost savings, but it has been limited by the injection volume of no greater than 2 mL for a long time. Recently, the adoption of hyaluronidase has become a plausible method to realize high-dose high-volume biopharmaceutical products for SC injection. Among the hyaluronidase family, the recombinant human PH20 appears to be the most reliable candidate with excellent efficacy and safety for co-formulation development. As of 2024, a total of eight hyaluronidase co-formulated biological products have been approved by regulatory authorities. This review article systematically summarized the commercial hyaluronidase co-formulated biopharmaceutics and highlighted the critical aspects of the development of future products regarding selection of hyaluronidase, formulation and process development, non-clinical evaluation, and clinical investigation. Of note, considering the uniqueness of each therapeutic agent, early and effective communication with regulatory authorities is of vital importance to successful development. Discussions were further Expanded to cover the combination of hyaluronidase co-formulations with large-volume handheld autoinjectors. The ultimate goal of this review is to provide a practical and comprehensive reference that will substantially contribute to the development of hyaluronidase co-formulated biopharmaceuticals, thereby advancing the field and benefiting patients worldwide.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113573"},"PeriodicalIF":10.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485517","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":"Corrigendum to “Enhanced antitumor and anti-metastasis efficiency via combined treatment with CXCR4 antagonist and liposomal doxorubicin” [Journal of Controlled Release, Volume 196 (2014), Pages 324–331].","authors":"Ling Mei,&nbsp;Yayuan Liu,&nbsp;Qianyu Zhang,&nbsp;Huile Gao,&nbsp;Zhirong Zhang,&nbsp;Qin He","doi":"10.1016/j.jconrel.2025.01.043","DOIUrl":"10.1016/j.jconrel.2025.01.043","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"380 ","pages":"Pages 1200-1201"},"PeriodicalIF":10.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-acting injectable nanoparticle formulation for sustained release of anti-TNF-α antibody therapeutic in ulcerative colitis treatment","authors":"Yicheng Zhang ,&nbsp;Ling Li ,&nbsp;Jiayuan Kong ,&nbsp;Yuanmuhuang Long ,&nbsp;Xiaoya Lu ,&nbsp;Christopher J. Erb ,&nbsp;Yurun Miao ,&nbsp;Sachin V. Kammula ,&nbsp;Jordan Popov ,&nbsp;Alexander J. Tinana ,&nbsp;Florin M. Selaru ,&nbsp;Hai-Quan Mao","doi":"10.1016/j.jconrel.2025.02.043","DOIUrl":"10.1016/j.jconrel.2025.02.043","url":null,"abstract":"<div><div>Inflammatory bowel diseases (IBD) are chronic, remitting, and relapsing conditions of the gastrointestinal tract with incompletely elucidated etiology. The anti-TNF-α mAbs represent one of aflash nanocomplexation and flash nanoprecipitation process, resulting in particles with a narrow size distribution and tunable release profile, with the longest in vitro release lasting over four months. These mAb-releasing NPs are then incorporated into hyaluronic acid hydrogel microparticles (MPs) to enhance tissue retention, thus extending the duration of mAb release in vivo. A single i.m. injection of the LAI can maintain the serum mAb level above the therapeutically effective concentration for over 100 days in healthy mice. In a 9-week study using a dextran sulfate-induced chronic colitis model, the anti-TNF-α LAI formulation demonstrates substantial therapeutic efficacy and a better safety profile than free mAb injections. This work demonstrates the effectiveness of this LAI system in maintaining a persistent serum mAb level and its potential as a versatile, safer, and effective delivery system for antibody therapeutics.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"380 ","pages":"Pages 1005-1016"},"PeriodicalIF":10.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468208","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":"YTHDF1-targeting nanoassembly reverses tumoral immune evasion through epigenetics and cell cycle modulation","authors":"Hongting Liu,&nbsp;Xichu Zhang,&nbsp;Fangchun Ding,&nbsp;Jingfang Pan,&nbsp;Hanxiang Zhu,&nbsp;Zhanwei Zhou,&nbsp;Minjie Sun","doi":"10.1016/j.jconrel.2025.02.070","DOIUrl":"10.1016/j.jconrel.2025.02.070","url":null,"abstract":"<div><div>YTHDF1, as a key m⁶A reader protein, is believed to be one of the key mechanisms leading to tumor cell immune evasion and resistance via promoting MHC-I degradation. We explore therapeutic strategies that combine iron metabolism regulation with epigenetic regulation. Here, a nanoassembly that integrates Deferasirox (DFX, an FDA-approved iron chelator) and YTHDF1 siRNA (known as PPD/siYTHDF1) has been developed, which jointly promotes cell cycle arrest in tumor cells by interfering with iron metabolism and knocking down YTHDF1 protein. At the same time, YTHDF1 deficiency inhibits the mRNA translation of lysosome-related proteins, upregulates MHC-I molecule expression (2.5-fold), reduces the degradation of internalized antigens, enhances T cell-mediated immune response, and ultimately restores tumor immune surveillance and triggers powerful anti-tumor immune efficacy. After treatment, CD8⁺ T cells in the tumor site increased by 2.2-fold, and effector memory T cells in the spleen increased by 2.1-fold. It demonstrates a highly effective anti-tumor effect in breast cancer treatment, as well as in postoperative anti-recurrence and anti-metastasis models.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113574"},"PeriodicalIF":10.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477466","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":"BioJect: An in vitro platform to explore release dynamics of peptides in subcutaneous drug delivery","authors":"David Li ,&nbsp;Qiuhua Qin ,&nbsp;Ayça Altay Benetti ,&nbsp;Lyes Kahouadji ,&nbsp;Matthias G. Wacker","doi":"10.1016/j.jconrel.2025.02.013","DOIUrl":"10.1016/j.jconrel.2025.02.013","url":null,"abstract":"<div><div>Predicting the release performance of subcutaneous (SC) drug formulations is challenging due to the complex interplay between physicochemical properties and the physiological microenvironment, which includes the extracellular matrix (ECM), fluid composition, and fluid availability, factors that collectively influence bioavailability and absorption rates. The ECM often acts as a bandpass filter modulated by local ion and protein content. In this study, we introduce the BioJect cell, a modern release test method based on the compendial flow-through cell, integrating a perfusion system with customizable biomatrix components. We systematically investigated the release mechanisms of four insulin formulations: regular human insulin, insulin aspart, insulin glulisine, and Neutral Protamine Hagedorn (NPH) insulin. A modified simulated subcutaneous interstitial fluid (mSSIF) comprising multiple components of the SC physiological environment was employed. It incorporates important ions and proteins (138.5 mM sodium, 10 mM potassium, 1.8 mM calcium, 0.8 mM magnesium, 111.3 mM chloride, 28 mM bicarbonate, 0.5 mM sulfate, 5 mM acetate, 4.2 mM phosphate, 30 g/L total protein added as bovine serum albumin). Our release test method discriminated the tested formulations under varying biorelevant conditions, demonstrating its biopredictive capabilities. Notably, we discovered a previously undocumented albumin binding affecting the release rate of insulin glulisine, likely occurring in the low-shear environment of SC tissue only. Additionally, the inclusion of biorelevant components like hyaluronic acid and collagen into the biomatrix of the BioJect cell provided profound insights into potential absorption and release mechanisms, supported by two <em>in vitro-in vivo</em> relationships (level C and level A). The BioJect cell represents a significant advancement in simulating the SC environment for drug release testing. Our findings highlight the importance of considering protein binding and ECM components in predicting drug absorption, offering a promising tool for the development and optimization of SC formulations.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"380 ","pages":"Pages 1058-1079"},"PeriodicalIF":10.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382385","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":"Transforming tumors into ‘high-risk bombs’ triggers a neoantigen storm and amplifies immune responses","authors":"Yunlong Li ,&nbsp;Quanwei Sun ,&nbsp;Zexin Yang ,&nbsp;Min Luo ,&nbsp;Wenshuo Yang ,&nbsp;Zhengwei Song ,&nbsp;Kang Liu ,&nbsp;Huihui Li ,&nbsp;Wenheng Gao ,&nbsp;Qinghua Wu ,&nbsp;Wei Shen ,&nbsp;Ye Yang ,&nbsp;Dengke Yin","doi":"10.1016/j.jconrel.2025.02.040","DOIUrl":"10.1016/j.jconrel.2025.02.040","url":null,"abstract":"<div><div>Although various immunotherapies have improved the treatment of several challenging malignancies in clinical applications, current research suggests that neoantigens remain fundamental to the initiation of immunotherapy, implying a dependence on high mutation loads in tumors and stable target antigens. To overcome these limitations, we propose a novel immunotherapy paradigm that interferes with splicing to induce the expression of neoantigens and neoepitopes while simultaneously blocking autophagy to prevent their degradation through endogenous pathways. This approach ensures the stable expression and accumulation of neoantigens and neoepitopes in tumor cells. To fully unleash the potential of neoantigens, we further induce tumors to undergo immunogenic cell death (ICD), triggering a “neoantigen storm” at the tumor site to recruit and activate more dendritic cells (DCs). Through a DC-dependent mechanism, communication between the tumor and the tumor-draining lymph node (TDLN) is enhanced, summoning more neoantigen-specific cytotoxic T lymphocytes to lyse tumor cells and establish immune circulation. In summary, this work presents a novel antigen-based immune sensitization strategy that stabilizes target antigens while exploring the potential of non-targeted antigens. By bypassing the cumbersome neoantigen identification process, this strategy holds promise for rapid clinical application in combination with other immunotherapies.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"380 ","pages":"Pages 1080-1094"},"PeriodicalIF":10.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458254","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":"Combining oxygen delivery and generation for targeted atherosclerosis therapy","authors":"Yujie Wang ,&nbsp;Qianru Zhou ,&nbsp;Le Lu ,&nbsp;Jianhua Xu ,&nbsp;Gang Yang ,&nbsp;Xuan Sun ,&nbsp;Xue Bao ,&nbsp;Lina Kang ,&nbsp;Pin Lv ,&nbsp;Renyuan Liu ,&nbsp;Biao Xu ,&nbsp;Qi Yang ,&nbsp;Dan Mu ,&nbsp;Bing Zhang","doi":"10.1016/j.jconrel.2025.02.053","DOIUrl":"10.1016/j.jconrel.2025.02.053","url":null,"abstract":"<div><div>Hypoxia plays an important role in the progression of atherosclerosis. However, ameliorating hypoxia at atherosclerotic lesions remains a great challenge. To achieve targeted oxygen delivery to atherosclerotic plaques, Lipid 5-doped, platelet membrane-encapsulated magnetic mesoporous organosilicon nanoparticles loaded with perfluoro-15-crown ether (PFCE) (FMMON@PL) were prepared. PFCE worked as an oxygen carrier, while iron oxide nanoparticles (IONPs) acted as nanozymes with catalase-like activity to facilitate oxygen generation. To enhance plaque targeting, platelet membranes were coated onto mesoporous organosilicon nanoparticles containing PFCE and IONPs. Lipid 5 containing a tertiary amine was doped into the platelet membranes for lysosomal escape. Our results demonstrated that FMMON@PL specifically targeted macrophages in atherosclerotic plaques. FMMON@PL significantly reduced HIF-1α expression, ameliorated oxidative stress, inhibited foam cell formation, and reduced M1 macrophage polarization. In conclusion, FMMON@PL successfully achieved oxygen delivery within plaques and inhibited plaque progression, demonstrating the feasibility of hypoxia alleviation for the treatment of atherosclerosis.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"380 ","pages":"Pages 1017-1030"},"PeriodicalIF":10.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}