Journal of Controlled Release最新文献

{"title":"Sensitizing ferroptotic and apoptotic cancer therapy via tailored micelles-mediated coenzyme and ATP depletion under hypoxia","authors":"Min Gao ,&nbsp;Yue Song ,&nbsp;Jing Liang ,&nbsp;Tiantian Chen ,&nbsp;Jiajia Luo ,&nbsp;Panyu Du ,&nbsp;Han Wang ,&nbsp;Hongyu Leng ,&nbsp;Zheng Wang ,&nbsp;Xinlong Ma ,&nbsp;Kai Wang ,&nbsp;Yanjun Zhao","doi":"10.1016/j.jconrel.2025.02.068","DOIUrl":"10.1016/j.jconrel.2025.02.068","url":null,"abstract":"<div><div>Concurrent induction of apoptosis and ferroptosis is promising in handling heterogenous cancers. We report a tailored polymeric micellar nanoplatform for the combinational anti-tumor therapy. Two stimuli-responsive amphiphlic block copolymers were synthesized, bearing three functional moieties, <em>i.e.</em> azobenzene, nitroimidazole and 3-fluorophenylboronic acid. Azobenzene could enhance the cellular uptake of micelles. Nitroimidazole and 3-fluorophenylboronic acid could deplete the reduced nicotinamide adenine dinucleotide phosphate (NADPH), glucose and adenosine triphosphate (ATP) under hypoxia, sensitizing ferroptotic and apoptotic cell death. The proof-of-concept was demonstrated in a triple-negative breast cancer cell line (MDA-MB-231). Irrespective of the free or encapsulated form, doxorubicin and auranofin showed a synergistic action, evidenced by a low combination index (&lt; 1). The co-delivery micelles showed improved potency than the single drug-loaded micelles in terms of the biomarkers of apoptosis (<em>e.g.</em> caspase 3/9, cytochrome <em>c</em> and ATP) and ferroptosis (<em>e.g.</em> thioredoxin reductase, thioredoxin, glutathione, NADPH, malondialdehyde and lipid peroxides). The apoptosis and ferroptosis induction ability of cargo-free micelles was proved. The <em>in vivo</em> efficacy was verified in the MDA-MB 231 tumor-bearing nude mice model. The current work offers a promising strategy of combinational anti-tumor drug delivery for potent induction of ferroptosis and apoptosis <em>via</em> the sensitization effect of vehicle in the hypoxic tumor.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113572"},"PeriodicalIF":10.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526089","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":"Emerging glucose oxidase-delivering nanomedicines for enhanced tumor therapy","authors":"Kaiyue Song ,&nbsp;Jiang Ming ,&nbsp;Bailong Tao ,&nbsp;Feng Zhao ,&nbsp;Shaorong Huang ,&nbsp;Wencheng Wu ,&nbsp;Cong Jiang ,&nbsp;Xianglong Li","doi":"10.1016/j.jconrel.2025.02.076","DOIUrl":"10.1016/j.jconrel.2025.02.076","url":null,"abstract":"<div><div>Abnormalities in glucose metabolism have been shown to characterize malignant tumors. Glucose depletion by glucose oxidase (GOD) has shown great potential in tumor therapy by causing tumor starvation. Since 2017, nanomedicines have been designed and utilized to deliver GOD for more precise and effective glucose modulation, which can overcome intrinsic limitations of different cancer therapeutic modalities by remodeling the tumor microenvironment to enhance antitumor therapy. To date, the topic of GOD-delivering nanomedicines for enhancing tumor therapy has not been comprehensively summarized. Herein, this review aims to provide an overview and discuss in detail recent advances in GOD delivery and directly involved starvation therapy strategies, GOD-sensitized various tumor therapy strategies, and GOD-mediated multimodal antitumor strategies. Finally, the challenges and outlooks for the future progress of the emerging tumor therapeutic nanomedicines are discussed. This review provides intuitive and specific insights to a broad audience in the fields of nanomedicines, biomaterials, and cancer therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113580"},"PeriodicalIF":10.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517919","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":"A novel scheme for non-invasive drug delivery with a magnetically controlled drug delivering capsule endoscope","authors":"Weijun Wang ,&nbsp;Kun Zhang ,&nbsp;Fanhua Ming ,&nbsp;Biao Chen ,&nbsp;Hao Zhang ,&nbsp;Zhe Wang ,&nbsp;Xin Jiang ,&nbsp;Hang Zhang ,&nbsp;Guochen Shang ,&nbsp;Yuhui Bao ,&nbsp;Hangyu Peng ,&nbsp;Shanshan Liu ,&nbsp;Xin Ling ,&nbsp;Wenhao Li ,&nbsp;Huanpeng Zhu ,&nbsp;Yurui Zhang ,&nbsp;Sicheng Cai ,&nbsp;Zhen Ding ,&nbsp;Rong Lin","doi":"10.1016/j.jconrel.2025.113591","DOIUrl":"10.1016/j.jconrel.2025.113591","url":null,"abstract":"<div><div>There is a lack of effective means for precise drug delivery of gastrointestinal diseases. Herein we report a novel magnetically controlled drug delivering capsule endoscope (MDCE) to achieve precision drug delivery for gastrointestinal diseases. MDCE integrates a drug delivery system into conventional capsule endoscope. It can carry 0.5 ml of liquid medication, which can be sprayed onto the target area using an electric pump upon detecting lesions by convolutional neural network (CNN)-model. Additionally, with the aid of an external magnet, the operator can adjust the posture and drug delivery direction of the capsule endoscope to enhance the accuracy of drug release. This adjustment process is monitored in real-time through the camera at the front of the capsule endoscope. To validate the clinical efficacy of the MDCE, we established porcine intestinal epithelial injury and bleeding models, and we demonstrated that MDCE could accurately deliver drugs under magnetic control through direct visualization. MDCE could significantly reduce injury area by delivering organoids to porcine injury sites after 7 days compared to the control group (48 mm² <em>vs.</em> 21 mm², <em>p</em> = 0.018). MDCE could significantly reduce bleeding time by spraying norepinephrine to porcine intestinal bleeding site compared to the control group (731 s <em>vs.</em> 418 s, <em>p</em> = 0.007). These demonstrate that MDCE could actively accurately release drugs under magnetic control through direct visualization in a non-invasive manner. This opens a new chapter for the precision treatment of gastrointestinal diseases and provides a novel approach for oral drug administration for systemic diseases.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113591"},"PeriodicalIF":10.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517922","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":"Combination therapy and drug co-delivery systems for atherosclerosis","authors":"Yingxuan Dai ,&nbsp;Li Yang ,&nbsp;Guosheng Cao ,&nbsp;Liqing Mo ,&nbsp;Can Yang ,&nbsp;Yuxi Zhu ,&nbsp;Yujie Guo ,&nbsp;Yi Hong ,&nbsp;Hanlin Xu ,&nbsp;Shan Lu ,&nbsp;Shi Du ,&nbsp;Jianhua He","doi":"10.1016/j.jconrel.2025.02.039","DOIUrl":"10.1016/j.jconrel.2025.02.039","url":null,"abstract":"<div><div>Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of plaque within the arteries. Despite advances in therapeutic strategies including anti-inflammatory, antioxidant, and lipid metabolism modulation treatments over the past two decades, the treatment of atherosclerosis remains challenging, as arterial damage is the result of interconnected pathological factors. Therefore, current monotherapies often fail to address the complex nature of this disease, leading to insufficient therapeutic outcomes. This review addressed this paucity of effective treatment options by comprehensively exploring the potential for combination therapies and advanced drug co-delivery systems for the treatment of atherosclerosis. We investigated the pathological features of and risk factors for atherosclerosis, underscoring the importance of drug combination therapies for the treatment of atherosclerotic diseases. We discuss herein mathematical models for quantifying the efficacy of the combination therapies and provide a systematic summary of drug combinations for the treatment of atherosclerosis. We also provide a detailed review of the latest advances in nanoparticle-based drug co-delivery systems for the treatment of atherosclerosis, focusing on the design of carriers with high biocompatibility and efficacy. By exploring the possibilities and challenges inherent to this approach, we aim to highlight cutting-edge technologies that can foster the development of innovative strategies, optimize drug co-administration, improve treatment outcomes, and reduce the burden of atherosclerosis-related morbidity and mortality on the healthcare system.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113543"},"PeriodicalIF":10.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476572","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":"Injectable biodegradable microchamber array films for long-term delivery of glucocorticoids","authors":"Jiaxin Zhang ,&nbsp;Jordan E Read ,&nbsp;Gayatri Mittal ,&nbsp;Robin N. Poston ,&nbsp;John Reilly ,&nbsp;Graeme Howling ,&nbsp;Ben Golland ,&nbsp;Gleb B. Sukhorukov ,&nbsp;David Gould","doi":"10.1016/j.jconrel.2025.113590","DOIUrl":"10.1016/j.jconrel.2025.113590","url":null,"abstract":"<div><div>Glucocorticoids (GCs) are widely recognized for their potent anti-inflammatory and analgesic effects. Although they can cause an array of side effects when delivered systemically these are generally avoided when delivered locally at disease sites such as the eyes, lungs and joints. Glucocorticoid formulations for local use range from crystals and particles through to non-biodegradable implants. In many formulations burst release means that their effectiveness does not persist for more than a few weeks. Novel delivery methods that achieve prolonged delivery of GCs along with sequential degradation of the polymer vehicle has the potential to enhance the effectiveness of these drugs and achieve better control of disease. In this study we use a soft lithography method to produce polymer microchamber array films (MCAs) containing crystals of GCs. We demonstrate that the rate of glucocorticoid release can be adjusted through the choice of polymer used in the manufacture of films with rapid release observed with PLGA 50/50 over the course of 9 weeks and the longest duration of release observed with PLA films which continued beyond a year. Importantly, these release studies do not show evidence of burst release and all films displayed a significant duration of zero order release kinetics. Observations of film degradation were made through changes in their size, microscopic appearance and liberation of lactic acid from the films during the course of experiments demonstrated the association with GC release kinetics. These flexible films can be rolled into fibers with little change in release kinetics and the rolled MCAs can also be injected <em>in vivo</em> through a syringe needle to a delivery site. We envisage that this study could lead to an innovative approach to achieve prolonged release of GCs from biodegradable formulations at disease sites.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113590"},"PeriodicalIF":10.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507494","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":"Investigating the stability of RNA-lipid nanoparticles in biological fluids: Unveiling its crucial role for understanding LNP performance","authors":"Heyang Zhang ,&nbsp;Matthias Barz","doi":"10.1016/j.jconrel.2025.02.055","DOIUrl":"10.1016/j.jconrel.2025.02.055","url":null,"abstract":"<div><div>Lipid nanoparticles (LNPs) are the most established and clinically advanced platform for RNA delivery. While significant efforts have been made to improve RNA delivery efficiency for improved protein production, the interplay between physiological stability, target specificity, and therapeutic efficacy of RNA-LNPs remains largely unexplored. This review highlights the crucial, yet often overlooked, impact of in vivo stability or instability of RNA-LNPs in contact with biological fluids on delivery performance. We discuss the various factors, including lipid composition, particle surface properties and interactions with proteins in physiological conditions, and provide an overview of the current methods for assessing RNA-LNP stability in biological fluids, such as dynamic laser light scattering, liquid chromatography, and fluorescent and radiolabeled techniques. In the final part, we propose strategies for enhancing stability, with a focus on shielding lipids. Therefore, this work highlights the importance of investigating and understanding the balance between stability and instability of LNPs in the biological context to achieve a more meaningful correlation between formulation properties and in vivo performance.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113559"},"PeriodicalIF":10.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507047","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 bioengineered platelets with internal doxorubicin loaded and external quercetin liposomes anchored for post-surgical tumor therapy","authors":"Qi Lu ,&nbsp;Zeyu Han ,&nbsp;Xia Wang ,&nbsp;Lili Du ,&nbsp;Xiaoyuan Fan ,&nbsp;Jian Zhao ,&nbsp;Ruihong Zhu ,&nbsp;Helin Wang ,&nbsp;Jiaxuan Song ,&nbsp;Wenwen Shen ,&nbsp;Haotian Zhang ,&nbsp;Zhonggui He ,&nbsp;Kaiyuan Wang ,&nbsp;Jin Sun","doi":"10.1016/j.jconrel.2025.02.042","DOIUrl":"10.1016/j.jconrel.2025.02.042","url":null,"abstract":"<div><div>Due to its natural tumor targeting ability, platelet-based drug delivery platform shows the great potential for tumor targeted treatment. However, both limited <em>in vitro</em> storage stability and rapid <em>in vivo</em> clearance rate severely restrict its clinical application. Here, utilizing the spatial structure of platelets precisely, chemotherapy drug doxorubicin (Dox) and liposomes-containing quercetin (Que) are loaded inside and anchored outside platelets, respectively, for establishing the engineered platelet platform (PDQLs). Dox plays the important role in inhibiting tumor growth, while Que mainly inhibits platelet apoptosis through activating serine/threonine protein kinase. PDQLs show the strong ability to resist external stimulation and physical damage. After being stored at room temperature for 4 days, more than 70 % of the platelets remain active. Given the natural wound tropism and tumor targeting abilities, the tumor accumulation of PDQLs is 1.02-fold higher than that of the solution. Base on the stealth characteristics of platelets and the continuous action of Que, PDQLs exhibit 10.63-fold increase area under the curve of solution. PDQLs can balance the anti-tumor recurrence and metastasis efficacy after surgery and safety. Our findings open a promising perspective and new sights for the development of bioengineered platelet platform in clinical application.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113546"},"PeriodicalIF":10.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472531","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":"Optimizing peptide nucleic acid-based pretargeting for enhanced targeted radionuclide therapy","authors":"Mohamed Altai ,&nbsp;Ábel Nagy ,&nbsp;Pauline Granit ,&nbsp;Wahed Zedan ,&nbsp;Myriam Cerezo-Magaña ,&nbsp;Julie Park ,&nbsp;Katharina Lückerath ,&nbsp;Susanne Geres ,&nbsp;Marie Sydoff ,&nbsp;Daniel L.J. Thorek ,&nbsp;Kristina Westerlund ,&nbsp;David Ulmert ,&nbsp;Amelie Eriksson Karlström","doi":"10.1016/j.jconrel.2025.02.047","DOIUrl":"10.1016/j.jconrel.2025.02.047","url":null,"abstract":"<div><div>Radiolabeled targeting agents have emerged as valuable tools for the treatment of disseminated cancer. Monoclonal antibodies (mAbs) are widely employed as carriers for diagnostic and therapeutic radionuclides due to their exceptional specificity and affinity. However, their prolonged circulatory half-life can diminish diagnostic efficacy and increase radiation exposure to non-target tissues in therapeutic applications, resulting in dose-limiting toxicities. To overcome this limitation, pretargeting technologies emerge as promising strategies to enhance tumor-to-background ratio and reduce radiation exposure of healthy tissues. Our previous work introduced a pretargeting concept leveraging the specific interaction between two peptide nucleic acid (PNA) probes, <em>HP1</em> and <em>HP2</em>, as the recognition mechanism. This early iteration of the PNA-based concept showed limited efficacy when used with mAb-based vectors. To improve its performance, we re-engineered the primary and secondary targeting agents by incorporating newly designed PNA-probes. As the primary targeting agent, we functionalized trastuzumab (T), a well-characterized human epidermal growth factor receptor 2 (HER2)-targeting IgG₁ mAb, with a 9-mer PNA probe (<em>HP9</em>). Both FcIII-based covalent UV-light crosslinking and enzyme-mediated glyco-engineering click-chemistry methods were applied to generate trastuzumab-PNA conjugates T-FcIII<em>-HP9</em> and T-gly<em>-HP9</em>, respectively. As a radionuclide-carrying secondary agent, we utilized a 9-mer complementary PNA probe, <em>HP16</em>, which forms a stable duplex with <em>HP9</em> as well as displaying favorable <em>in vivo</em> kinetics. Biacore and flow cytometry assessment of the <em>HP9-</em>conjugated trastuzumab agents demonstrated retained HER2-binding properties. The secondary <em>HP16</em> probe, labeled with either a dye or a radionuclide, showed cell surface accumulation contingent on the presence of <em>HP9</em> on the primary HER2-targeting agents. <em>In vivo</em>, T-gly<em>-HP9</em> exhibited significantly longer blood circulation half-life and superior tumor uptake compared to T-FcIII-<em>HP9</em>. Further, therapeutic dosing with [¹⁷⁷Lu]-<em>HP16</em> of trastuzumab-<em>HP9</em> pretargeted HER2+ tumor models resulted in significantly delayed disease progression and extended survival compared to untreated subjects. Furthermore, pretargeted [¹⁷⁷Lu]-<em>HP16</em> exhibited comparable efficacy to [¹⁷⁷Lu]-trastuzumab in both delaying disease progression and prolonging survival. In conclusion, the optimization of our PNA-based pretargeting system has resulted in exceptional <em>in vivo</em> targeting characteristics and therapeutic efficacy, validating the potential of this novel approach.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113551"},"PeriodicalIF":10.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476579","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":"Advances in polymer nanomaterials targeting cGAS-STING pathway for enhanced cancer immunotherapy","authors":"Shiyu Peng ,&nbsp;Xiaoxue Hou ,&nbsp;Jianfeng Liu,&nbsp;Fan Huang","doi":"10.1016/j.jconrel.2025.02.056","DOIUrl":"10.1016/j.jconrel.2025.02.056","url":null,"abstract":"<div><div>Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway has been recognized as a promising target for cancer immunotherapy. Although various STING agonists have been developed, their clinical applications are still severely impeded by various issues, such as non-specific accumulation, adverse effects, rapid clearance, etc. In recent years, the emergence of nanomaterials has profoundly revolutionized STING agonists delivery, which promote tumor-targeted delivery, boost the immunotherapeutic effects and reduce systemic toxicity of STING agonists. In particular, polymer nanomaterials possess inherent advantages including controllable structure, tunable function and degradability. These properties afford them the capacity to serve as delivery vehicles for small-molecule STING agonists. Furthermore, the superior characteristics of polymer nanomaterials can enable their utilization as a novel STING agonist to stimulate anti-tumor immunity. In this review, the molecular mechanisms of cGAS-STING pathway activation are discussed. The recent development of small-molecules STING agonists is described. Then polymer nanomaterials are discussed as carriers for STING agonists in cancer immunotherapy, including polymersomes, polymer micelles, polymer capsules, and polymer nanogels. Additionally, polymer nanomaterials are identified as a novel class of STING agonists for efficient cancer immunotherapy, encompassing both polymer materials and polymer-STING agonists conjugates. The review also presents the combination of polymer-based cGAS-STING immunotherapy with chemotherapy, radiotherapy, phototherapy (both photodynamic and photothermal), chemodynamic therapy, and other therapeutic strategies. Furthermore, the discussion highlights recent advancements targeting the cGAS-STING pathway in clinically approved polymer nanomaterials and corresponding potent innovations. Finally, the potential challenges and perspectives of polymer nanomaterials for activating cGAS-STING pathway are outlined, emphasizing the critical scientific issue and hoping to offer guidance for their clinical translation.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113560"},"PeriodicalIF":10.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507046","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":"Maltodextrin-driven MOF Nano-antibacterial system for effective targeted bacteria and enhancing photodynamic therapy in bacterial keratitis","authors":"Lifang Chen ,&nbsp;Yao Wang ,&nbsp;Xiuqing Huang ,&nbsp;Lifang Han ,&nbsp;Zhengwei Huang ,&nbsp;Ling Guo ,&nbsp;Kai Chen ,&nbsp;Guoxin Tan","doi":"10.1016/j.jconrel.2025.02.031","DOIUrl":"10.1016/j.jconrel.2025.02.031","url":null,"abstract":"<div><div>The occurrence of bacterial keratitis (BK) presents a significant threat to ocular health, often leading to visual impairment. Currently, conventional antibiotic therapies tend to promote bacterial resistance and lack biocompatibility. Therefore, it is of great significance to develop an alternative product with safe and efficient antimicrobial properties. In this study, we developed a novel smart pH-responsive nano-antibacterial system (PM/Ag-Ce6@ZIF-8) based on a metal-organic framework (MOF), enabling specific bacterial targeting and photodynamic therapy. By utilizing bacteria-specific maltodextrin transport pathway, the intelligent nano-antibacterial modified with maltotriose can accurately discriminate between bacterial infection and normal tissue, specifically target the site of infection, and efficiently accumulate at the infection site to enhance safety and efficacy. Furthermore, the incorporation of silver nanoparticles enhances the effectiveness of MOF photodynamic therapy by effectively eradicating bacteria. The nano-antibacterial system exhibits potent inhibition of biofilm formation as well as antibacterial activity while demonstrating excellent in vitro and in vivo biocompatibility. In an animal model of bacterial keratitis, PM/Ag-Ce6@ZIF-8 exhibits superior antibacterial activity compared to Levofloxacin (LVFX) eye drops, significantly improving therapeutic outcomes for bacterial keratitis in mice. Hence, this intelligent nano-antibacterial platform holds promising potential for clinical applications in treating keratitis.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"380 ","pages":"Pages 1164-1183"},"PeriodicalIF":10.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425425","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}