Journal of Controlled Release最新文献

{"title":"Ultrasound-responsive release of CD39 inhibitor overcomes adenosine-mediated immunosuppression in triple-negative breast cancer","authors":"Yijie Chen ,&nbsp;Yue Song ,&nbsp;Chao Zhang ,&nbsp;Peile Jin ,&nbsp;Yuhan Fu ,&nbsp;Guowei Wang ,&nbsp;Lina Tang ,&nbsp;Jifan Chen ,&nbsp;Xiaodan Xu ,&nbsp;Pintong Huang","doi":"10.1016/j.jconrel.2025.113819","DOIUrl":"10.1016/j.jconrel.2025.113819","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC), an exceptionally aggressive subtype of breast cancer, is characterized by a poor prognosis and limited treatment options. Although immunotherapy has shown promise for the treatment of TNBC, the immunosuppressive accumulation of adenosine (ADO) in the tumor microenvironment (TME) contributes to immune evasion and tumor progression. To address this challenge, we introduce a novel ultrasound-responsive liposomal system (BFPL) designed to inhibit ADO production and enhance the effectiveness of sonoimmunotherapy. BFPL consists of lipid membranes loaded with an endoplasmic reticulum (ER)-targeting sonosensitizer (PMPS) and a reactive oxygen species (ROS)-responsive CD39 inhibitor (FPL-67156) polyplex, synthesized <em>via</em> the thin-film hydration method. Upon ultrasound irradiation, BFPL generates substantial ROS, inducing robust immunogenic cell death (ICD) through ER stress. Concurrently, ROS-mediated deboronation of the polyplex releases FPL-67156, which inhibits ATP degradation into ADO, thereby promoting dendritic cell maturation and activating effector T cells. Moreover, BFPL effectively triggers a potent antitumor immune response and enhances the efficacy of anti–PD-L1 immunotherapy. Thus, by modulating metabolic pathways to counteract ADO-associated barriers in ICD therapy, this innovative approach holds potential for improving immunotherapy outcomes in TNBC.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113819"},"PeriodicalIF":10.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915485","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":"Neutrophil membrane engineered human umbilical cord MSC-derived sEVs enhance anti-tumor efficacy for gastric cancer via delivering pentraxin 3","authors":"Yuting Tang ,&nbsp;Ye Shen ,&nbsp;Xueyan Zang ,&nbsp;Peipei Wu ,&nbsp;Linli Li ,&nbsp;Hui Qian ,&nbsp;Xu Zhang ,&nbsp;Wenrong Xu ,&nbsp;Jiajia Jiang","doi":"10.1016/j.jconrel.2025.113828","DOIUrl":"10.1016/j.jconrel.2025.113828","url":null,"abstract":"<div><div>Gastric cancer poses a significant global health challenge, promoting ongoing updates and exploration of treatment strategies. In this study, we proposed the naïve human umbilical cord mesenchymal stem cell derived small extracellular vesicles (hucMSC-sEVs) effectively inhibit gastric cancer proliferation and migration, presenting a promising bioactive agent for gastric cancer therapy. To address the issues of shortage in circulation time, limited targeting efficiency, suboptimal therapeutic outcomes associated with hucMSC-sEVs, we engineered a membrane fusion between hucMSC-sEVs with human neutrophil membrane, creating Neu/MSC-sEVs. This modification enhanced tumor cell targeting, reduced clearance by the mononuclear macrophage system, prolonged circulation time, and improved therapeutic efficacy. Furthermore, inhibiting the tumor suppressor protein pentraxin 3 (PTX3) in hucMSC-sEVs attenuated their anti-tumor effects, indicating that enrichment with PTX3 enhances the tumor-inhibiting potential of hucMSC-sEVs. Overall, our findings shed light on the mechanism by which hucMSC-sEVs exert their therapeutic effects on gastric cancer and underscore the importance of vesicle modification in enhancing targeting precision and therapeutic outcomes. These findings provide new insights for clinical application of modified vesicles in cancer treatment.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113828"},"PeriodicalIF":10.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915562","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":"Content list including Graphcal Abstracts","authors":"","doi":"10.1016/S0168-3659(25)00428-6","DOIUrl":"10.1016/S0168-3659(25)00428-6","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113808"},"PeriodicalIF":10.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912325","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":"Programmable hierarchical hydrogel dressing for sequential release of growth factor and DNase to accelerate diabetic wound healing","authors":"Ying Zhang ,&nbsp;Shiqi Lin ,&nbsp;Xiao Xu ,&nbsp;Yufan Yao ,&nbsp;Shufan Feng ,&nbsp;Sida Jiang ,&nbsp;Yuqian Wang ,&nbsp;Wei He ,&nbsp;Ran Mo","doi":"10.1016/j.jconrel.2025.113825","DOIUrl":"10.1016/j.jconrel.2025.113825","url":null,"abstract":"<div><div>Dysregulation of growth factor expression causes impaired healing of diabetic foot ulcer (DFU). Platelet-derived growth factor (PDGF)-containing gel has been clinically applied for topical treatment of DFU. Recruitment of neutrophils stimulated by PDGF favors the wound healing of DFU. However, overactivation of neutrophils induced by hyperglycemia causes massive generation and long-term persistence of neutrophil extracellular traps (NETs), ultimately leading to unexpected skin damage and delayed wound repair. Here, we engineer a hierarchically-assembled hydrogel to achieve local release of the growth factor, PDGF-BB and the NET scavenger, deoxyribonuclease (DNase) I with distinct kinetics for enhanced healing of DFU. The hydrogel is constructed by crosslinking of anti-bacterial quaternized chitosan and hypochlorite-degradable nanogel via a copper-free click reaction, in which PDGF-BB is loaded in the hydrogel matrix while DNase I is encapsulated in the inner nanogel. Programmable release of combinatorial therapeutics is implemented by the hydrogel in response to the wound microenvironment. We show that the hierarchical hydrogel co-loaded with PDGF-BB and DNase I promotes neutrophil recruitment, increases endothelial cell migration, degrades excess NETs, and prevents wound infection for accelerating the wound closure in the diabetic mouse wound models.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113825"},"PeriodicalIF":10.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909881","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":"Novel in vitro model for intravitreal drug dissolution and release studies of small molecules and their long-acting formulations","authors":"Teemu Sorsa ,&nbsp;Eva M. del Amo ,&nbsp;Amir Sadeghi ,&nbsp;Jonna Laitinen ,&nbsp;Iuliia Pilipenko ,&nbsp;Arto Urtti ,&nbsp;Astrid Subrizi","doi":"10.1016/j.jconrel.2025.113823","DOIUrl":"10.1016/j.jconrel.2025.113823","url":null,"abstract":"<div><div>Intravitreal drug delivery is essential for multiple ocular diseases. Development of intravitreal formulations requires high-quality <em>in vivo</em> experiments that require a large number of animals. This development can be expedited by improving <em>in vitro</em> testing and utilizing <em>in vitro</em> – <em>in vivo</em> correlation. We propose an <em>in vitro</em> approach using vitreous in a dialysis membrane to conduct these studies. The model was developed for small molecules and evaluated with drugs in solution (13 drugs in one cassette and 4 in another), and a drug suspension. For solutions, 6 out of 8 drug compounds were within 2.5-fold difference to their experimental vitreal clearances. Furthermore, we demonstrated suitability of the model for long-acting formulations in a 150-day experiment with triamcinolone acetonide suspension. The suspension displayed similar elimination trend as has been observed in rabbits. We believe this system can lead the way in introducing site-specific drug release testing for the intravitreal route.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113823"},"PeriodicalIF":10.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909971","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":"Virus-mimicking nanoparticle potentiates in-situ cancer vaccines by reversing intratumoral DCs via stimulating cytosolic nucleic acid sensors","authors":"Ya Chu ,&nbsp;Luyao Wang ,&nbsp;Xi Huang ,&nbsp;Cenxi Lao ,&nbsp;Lin Luo ,&nbsp;Jingyi Chen ,&nbsp;Fangfei Jin ,&nbsp;Lili Zhao ,&nbsp;Kaiyuan Hu ,&nbsp;Miao Lv ,&nbsp;Xianjing Li ,&nbsp;Yong Yang ,&nbsp;Weijun Zhao ,&nbsp;Wenguang Wang","doi":"10.1016/j.jconrel.2025.113801","DOIUrl":"10.1016/j.jconrel.2025.113801","url":null,"abstract":"<div><div>The major challenge for in-situ cancer vaccines is to activate the dendritic cells (DCs) within the immunosuppressive tumor to initiate tumor-specific immune responses. By contrast, oncolytic viruses can always activate intratumoral DCs to initiate virus-specific immunity to eliminate viruses which will in turn reduce the anti-tumor effect of these viruses. To bridge the two approaches, we developed virus-mimicking nanoparticle (V-mimic) through self-assembly of artificial cyclic gadolinium-based GAMP (c·Gd·GAMP, a STING agonist), double-stranded RNA analog (Poly I:C), and indocyanine green (ICG). Within the V-mimic, c·Gd·GAMP and Poly I:C can simulate the DNA and RNA produced by virus replication to reverse the inhibition of the immunosuppressive tumor microenvironment on DCs by promoting the IFN-β secreting via activating nucleic acid sensors, thereby eliciting anti-tumor immune response in a manner akin to the immune response triggered by viruses. Notably, the V-mimic significantly promoted IFN-β secretion, enhanced DCs maturation, and elicited robust tumor-specific immune memory when combined with photothermal therapy. In multiple tumor models, significant tumor inhibition was observed, including a metastasis and recurrence model. Therefore, leveraging the virus-mimicking nanoparticle to simulate the mechanism of virus-initiated specific immune responses to activate the intratumoral DCs may open up new strategies for in-situ cancer vaccines.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113801"},"PeriodicalIF":10.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909880","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":"Nanogel encapsulation improves pharmacokinetics and biodistribution of antimicrobial peptide LL37 upon lung deposition: In vivo evaluation by SPECT/CT","authors":"Sylvia N. Kłodzińska ,&nbsp;Tullio V.F. Esposito ,&nbsp;Monica Agnoletti ,&nbsp;Cristina Rodríguez-Rodríguez ,&nbsp;Colin Blackadar ,&nbsp;Lan Wu ,&nbsp;Aneesh Thakur ,&nbsp;Jessica Nahrstedt ,&nbsp;Thomas Rades ,&nbsp;Katayoun Saatchi ,&nbsp;Urs O. Häfeli ,&nbsp;Hanne Mørck Nielsen","doi":"10.1016/j.jconrel.2025.113817","DOIUrl":"10.1016/j.jconrel.2025.113817","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) constitute the first line of defense in the human body and exogenous application of AMPs is a desirable therapeutic strategy to combat bacterial infections. However, the antibacterial properties of AMPs are often time limited due to fast degradation by host and bacterial proteases, and administration of the needed high doses may result in local inflammation, as well as nephro- and hepatotoxicity. In this study, we assessed the possibility of using nanogels composed of hyaluronic acid modified with octenyl succinic anhydride (HA-OSA) as a drug delivery system to improve the pharmacokinetics and safety profile of LL37, a naturally occurring AMP, when administered to the mucosal surface of the lungs. The peptide LL37 and the polymer HA-OSA were radiolabeled with ⁶⁷gallium and ¹¹¹indium, respectively, allowing for non-invasive tracking over time in mice following intratracheal administration. When non-formulated LL37 was administered, approximately 85 % of the peptide dose was cleared from the lungs over 48 h, whereas encapsulation of LL37 in HA-OSA nanogels increased peptide retention in the lungs by 36 %. Additionally, the amount of peptide in excretory organs was reduced, decreasing potential liver and kidney toxicity known to be associated with AMP-based therapies. The findings in this study indicate that encapsulation of LL37 in nanogels provides beneficial pharmacokinetic effects.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113817"},"PeriodicalIF":10.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915489","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":"Impact of pre-existing anti-polyethylene glycol (PEG) IgM on biodistribution and humoral response of intramuscularly administered PEGylated mRNA loaded lipid nanoparticle","authors":"Shunji Abe ,&nbsp;Haruka Takata ,&nbsp;Taro Shimizu ,&nbsp;Yoshino Kawaguchi ,&nbsp;Shoichiro Fukuda ,&nbsp;Haruka Yamamoto ,&nbsp;Hidenori Ando ,&nbsp;Tatsuhiro Ishida","doi":"10.1016/j.jconrel.2025.113821","DOIUrl":"10.1016/j.jconrel.2025.113821","url":null,"abstract":"<div><div>With the approval of mRNA vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lipid nanoparticles (LNP) have emerged as a powerful tool for nucleic acid delivery. Modification of LNP with polyethylene glycol (PEG)-lipids contributes to their <em>in vitro</em> and <em>in vivo</em> stability by reducing aggregation of the particles. Despite the general acknowledgement of the low immunogenicity of PEG, there are numerous reports of the occurrence of anti-PEG antibodies in the blood of healthy individuals. Furthermore, there are reports that pre-existing anti-PEG IgM antibodies attenuated the efficacy of PEG-modified drugs administered systemically. Skeletal muscles, the administration site for mRNA vaccines, are highly vascularized by a network of blood vessels to provide them with nutrients and oxygen. Since skeletal muscles can contain circulating anti-PEG antibodies or the administered mRNA-LNP extravasate into bloodstream, the purpose of this study was to evaluate the effects of pre-existing anti-PEG IgM on the protein translation, biodistribution, and humoral responses to mRNA-loaded LNP (mRNA-LNP) administered intramuscularly (i.m.) in mice. We found that the presence of anti-PEG IgM in blood has only a minor effect on the translation and distribution of mRNA-LNP in the localized muscle area where the mRNA-LNP were administered. Circulating anti-PEG IgM did not increase the total accumulation of mRNA-LNP in the liver, but did markedly diminish its protein translation because the mRNA-LNP were delivered primarily to Kupffer cells rather than to hepatocytes. Binding of anti-PEG IgM to mRNA-LNP, and subsequent complement activation, suppressed mRNA translation loaded in LNP in the liver. Repeated intramuscular injections of SARS-CoV-2 Spike protein mRNA-LNP elicited a robust immune response. Our results indicate that the presence of circulating anti-PEG IgM does not interfere with the efficiency of mRNA vaccines administered i.m. in mice. We can speculate that non-specific translation of mRNA vaccines in somatic cells may be inhibited <em>in vivo</em> by circulating anti-PEG IgM, reducing adverse effects such as hepatitis and myocarditis that are caused by immune responses against translated antigen proteins.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113821"},"PeriodicalIF":10.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909878","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":"Homologous magnetic targeted immune vesicles for amplifying immunotherapy via ferroptosis activation augmented photodynamic therapy against glioblastoma","authors":"Hanwen Zhang ,&nbsp;Kuanhan Feng ,&nbsp;Mingzhi Han ,&nbsp;Yali Shi ,&nbsp;Yingjie Zhang ,&nbsp;Jie Wu ,&nbsp;Wanyi Yang ,&nbsp;Xinrui Wang ,&nbsp;Liuqing Di ,&nbsp;Ruoning Wang","doi":"10.1016/j.jconrel.2025.113816","DOIUrl":"10.1016/j.jconrel.2025.113816","url":null,"abstract":"<div><div>In spite of noteworthy breakthroughs in clinical treatments, immune checkpoint blockade (ICB) therapy is often hindered by T lymphocyte dysfunction in the immunosuppressive microenvironment of glioblastoma (GBM). Herein, GBM-derived exosomes (GBM-Exos) co-encapsulate ferroptosis inducer arsenic trioxide (ATO) and NIR photosensitizer IR780, modified with superparamagnetic iron oxide nanoparticle (SPION), to construct homologous magnetic targeted immune vesicles (Sp-Exo/AI) for reinvigorating anti-tumor immunity. SPION modified GBM-Exos display capacities of tumor accumulation and blood-brain barrier penetration. Notably, reactive oxygen species metabolism is disturbed by ferroptosis activation augmented photodynamic therapy (PDT), hence triggering tumor cell lysis and mitochondrial damage to reshape tumor microenvironment (TME) and transform GBM from immune “cold” to “hot”. Accordingly, the tumor specific T lymphocytes function and phenotype transformation of macrophages were promoted to stimulate robust innate and adaptive immunities. Significantly, the remarkable ferroptosis activation augmented PDT combining with programmed death-1 antibody actives long-term immune memory and inhibits distal tumor metastasis. Superior anti-tumor effect of Sp-Exo/AI in the recurrence model, breast cancer model and patient-derived model were observed as well. Altogether, the presented homologous magnetic targeted immune vesicles exhibit substantial potential for amplifying immune response in “cold” tumors like GBM through revising immunosuppressive TME.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113816"},"PeriodicalIF":10.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909973","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":"Dual-functional hCe-pHEMA contact lenses for ocular antibiotic release, antioxidant protection, and in vivo corneal bacterial infection treatment","authors":"Zhao Wang ,&nbsp;Xiaomei Wang ,&nbsp;Yao Zhou ,&nbsp;Xiaojuan Zhang ,&nbsp;Yong Bian ,&nbsp;Qing Lin ,&nbsp;Yujie Wang ,&nbsp;Ruilong Sheng","doi":"10.1016/j.jconrel.2025.113813","DOIUrl":"10.1016/j.jconrel.2025.113813","url":null,"abstract":"<div><div>Ocular bacterial infections are typically associated with elevated levels of reactive oxygen species (ROS). Nevertheless, for treating ocular bacterial keratitis (BK), broad-spectrum antibiotics in eye drops or ointments are unable to inhibit ROS and encounter swift clearance and reduced bioavailability. This work developed antibiotic levofloxacin (LEV)-loaded hollow ceria nanoparticles (hCe NPs, ROS scavengers), which were embedded into poly-hydroxyethyl methacrylate (pHEMA) hydrogels to prepare dual-functional contact lenses (LEV@hCe-pHEMA), enabling extended ocular drug delivery and enhanced bioavailability. The integration of LEV@hCe NPs within pHEMA contact lenses preserved good optical transmittance (&gt; 90.0 %), fortified UV-blocking capacities (200–400 nm), achieved controllable LEV release (84.2 % within 120 h), and enhanced ROS scavenging-antioxidative potential (78.4 % within 60 min). <em>In vitro</em> cytotoxicity evaluations revealed low cytotoxicity (cell viability &gt;95.0 %) of the hCe-pHEMA contact lenses and affirmed their good biocompatibility. Notably, LEV@hCe-pHEMA exhibited significant antibacterial efficacy against <em>S. aureus</em> ATCC29213 (89.8 %) and <em>E. coli</em> ATCC25922 (94.2 %), demonstrating their therapeutic potential. <em>In vivo</em> safety evaluations in rabbit models showed no ocular irritation or pathological changes during a 7-day wearing period, confirming the good biocompatibility of the hCe-pHEMA lenses. LEV@hCe-pHEMA contact lenses could be utilized to treat rabbit BK model induced by <em>S. aureus</em>. It could near-completely remove the keratitis (within 7 days), reducing corneal edema and further recovering corneal transparency. The results suggested that LEV@hCe-pHEMA contact lenses could be employed as promising dual-functional smart ocular drug delivery systems for non-invasive ocular therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113813"},"PeriodicalIF":10.5,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905721","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}