Journal of Controlled Release最新文献

{"title":"Injectable microenvironment-responsive hydrogels encapsulating engineered NF-κB-targeting circular RNA for osteoarthritis therapy","authors":"Meng Li ,&nbsp;Xumiao Jia ,&nbsp;Penghui Lai ,&nbsp;Yuqian Ma ,&nbsp;Fei Li ,&nbsp;Lingyan Yang ,&nbsp;Siyuan Zhang ,&nbsp;Chongfei Yang ,&nbsp;Yu Luo ,&nbsp;Qinhao Wang","doi":"10.1016/j.jconrel.2025.114039","DOIUrl":"10.1016/j.jconrel.2025.114039","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a prevalent joint disease characterized by cartilage degeneration and an imbalance in subchondral bone homeostasis. Effective topical treatment of OA remains challenging due to the insufficient long-term efficacy, instability, and rapid clearance of therapeutic agents. In this study, we targeted the overactive NF-κB signaling in OA by introducing a P65 super repressor gene (srIκBα) as a circular RNA (circRNA), encapsulated within modified lipid nanoparticles (LNPs), and embedded in a silk fibroin composite hydrogel (SHC) cross-linked with matrix metalloproteinase (MMP)-sensitive substrate peptides. Consequently, we developed an environment-responsive intelligent drug delivery system, namely, circ-srIκBα@LNP-SHC, and the performance of this system was evaluated both <em>in vitro</em> and <em>in vivo</em>. It demonstrated potent targeting effects on chondrocytes and fibroblast-like synoviocytes (FLS) <em>in vitro</em>, with significantly inhibiting NF-κB signaling. In an OA rat model, circ-srIκBα@LNP-SHC exhibited superior anti-OA efficacy and cartilage repair capability, and markedly suppressed the expression of OA-related inflammatory mediators and matrix-degrading enzymes, and reversed the OA-associated gene expression profile. The therapeutic effect was further validated using human OA cartilage cultured <em>ex vivo</em>. In conclusion, our environmentally responsive drug delivery system based on circ-srIκBα shows significant potential for OA treatment, offering improved cell specificity, stability, and low immunogenicity, which may provide a novel strategy for OA management.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114039"},"PeriodicalIF":10.5,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611392","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 “Nucleic acid-based nanogels with ‘offensive and defensive’ effects for enhanced chemo-immunotherapy” [Journal of Controlled Release 385 (2025) 113977]","authors":"Zijian Zhao ,&nbsp;Fei Sun ,&nbsp;Wenyu Wang ,&nbsp;Bing Li ,&nbsp;Yan Liang ,&nbsp;Dengshuai Wei ,&nbsp;Yong Sun ,&nbsp;Jianqin Yan","doi":"10.1016/j.jconrel.2025.114024","DOIUrl":"10.1016/j.jconrel.2025.114024","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114024"},"PeriodicalIF":10.5,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605392","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":"Comparative study on the redox-responsive properties and antitumor efficacy of polyurethane nanocarriers with mono-, Di-, and trisulfide bonds","authors":"Jiaxin Wu, Shuai Yang, Yuyue Xiong, Jiacheng Liu, Zhongkui Wu, Ruogu Qi, Lesan Yan","doi":"10.1016/j.jconrel.2025.114035","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.114035","url":null,"abstract":"Polyurethane (PU) is considered an ideal nanocarrier for drug delivery due to its excellent biocompatibility and efficient drug-loading capacity. Sulfur bonds (such as monosulfide, disulfide, and trisulfide bonds), have attracted considerable attention in drug delivery systems due to their redox-responsive properties. However, current research primarily focuses on the application of sulfur bonds in prodrug nanoassemblies, where designs rely on specific chemical conjugation groups, limiting their applicability to a narrow range of drug molecules and thus restricting broader utility. Integrating sulfur bonds into polyurethane structures offers a promising approach to enhance carrier biocompatibility while significantly expanding their versatility for delivering various hydrophobic small-molecule drugs. Nevertheless, whether sulfur bonds retain their inherent redox-responsive behavior within a polyurethane requires systematic validation. To address this, we designed and synthesized three amphiphilic polyurethane materials incorporating monosulfide, disulfide, and trisulfide bonds as core components. These polymers self-assembled into nanomicelles, enabling a systematic comparison of their redox-responsive properties. Furthermore, the hydrophobic anticancer drug doxorubicin (DOX) was encapsulated as a model payload to evaluate the <em>in vivo</em> antitumor efficacy of the resulting drug-loaded nanomicelles. Our findings demonstrate that the incorporation of sulfur bonds markedly enhances the redox responsiveness of polyurethane nanocarriers, with the trisulfide bonds exhibiting the most pronounced reduction-sensitive behavior. This study provides deep insights into the influence of sulfur bonds type on the redox-responsive behavior of polyurethane nanomicelles and underscores the exceptional potential of trisulfide bonds in developing redox-responsive polyurethane-based nanocarriers for drug delivery. These results offer critical theoretical and experimental foundations for the design and optimization of smart polyurethane-based drug delivery systems.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"21 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611396","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)00634-0","DOIUrl":"10.1016/S0168-3659(25)00634-0","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"384 ","pages":"Article 114013"},"PeriodicalIF":10.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587981","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":"Targeted delivery of therapeutics to metastatic lung cancer cells using aptamer-conjugated nanoemulsions","authors":"Jenifer García-Fernández ,&nbsp;Sandra Díez-Villares ,&nbsp;María Cascallar ,&nbsp;Laura Rivadulla Costa ,&nbsp;Ana S. Martins ,&nbsp;Soraya Groba de Antas ,&nbsp;Maria Cristina Tarasco ,&nbsp;Elvira Pantano ,&nbsp;Giulia Taiè ,&nbsp;Giulia Bertolini ,&nbsp;Marta García-Hernández ,&nbsp;Miguel Moreno ,&nbsp;M. Elena Martín ,&nbsp;Ester Munera-Maravilla ,&nbsp;Silvia Calabuig-Fariñas ,&nbsp;Laura Taina-González ,&nbsp;Miguel G. Blanco ,&nbsp;Rafael López-López ,&nbsp;Alar Ainla ,&nbsp;Sara Abalde-Cela ,&nbsp;María de la Fuente Freire","doi":"10.1016/j.jconrel.2025.114031","DOIUrl":"10.1016/j.jconrel.2025.114031","url":null,"abstract":"<div><div>Lung cancer is the primary cause of cancer-related deaths, with a five-year overall survival rate of 15 %, mainly related to late diagnosis at advanced stages. Despite recent improvements in cancer medicine, metastatic disease still, in fact, represents the main challenge for effective therapies. Targeting disseminated cells requires a better understanding of the underlying biological mechanisms and a paradigm shift to devise innovative treatments.</div><div>Nanomedicine could open up new perspectives in cancer management, as nanoparticles offer many advantages in drug delivery due to their intrinsic properties, such as better bioavailability and the potential for selective targeting. A strategy to enhance delivery at the site of action is to use nanomedicines targeting specific receptors overexpressed in cancer cells or the tumor microenvironment. We recently identified TAS1R3 as an ideal target, enriched in metastatic lung cancer cells and highly expressed in the CD133+ cancer stem cell (CSC) subset.</div><div>We developed and evaluated a targeted formulation of sphingomyelin nanoemulsions functionalized with a TAS1R3-specific aptamer (SN-5F). SN-5F exhibited high stability in both aqueous media and biofluids and was efficiently internalized by cell models overexpressing the targeted receptor, including the usually hard-to-target CD133+ CSC population. SN-5F was evaluated in 2D and 3D cell cultures, as well as in vivo using patient-derived xenografts, where it successfully reached disseminated cancer cells and delivered hydrophobic drugs to CSCs, resulting in reduced tumor-forming potential.</div><div>These results highlight the promise of rationally designed, receptor-targeted nanomedicines as a novel approach for anti-metastatic lung cancer therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114031"},"PeriodicalIF":10.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594601","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":"Therapeutic nanoparticle safety in pregnancy: Bridging knowledge gaps with environmental insights and a translational roadmap","authors":"Julia Felsenstein ,&nbsp;Katherine M. Nelson ,&nbsp;Jasmine Shirazi ,&nbsp;Jason P. Gleghorn","doi":"10.1016/j.jconrel.2025.114026","DOIUrl":"10.1016/j.jconrel.2025.114026","url":null,"abstract":"<div><div>The use of nanoparticles (NPs) for therapeutic applications is an expanding field that has more recently begun to focus on pregnancy-related disorders. As the range of medical applications and the types of particles considered for therapeutic use expands, a detailed understanding of the possible risks of exposure during pregnancy is imperative. This review will examine how NP exposure can directly and indirectly affect placental growth and fetal development, as well as its effects on postnatal growth, and summarize the current research on NPs as drug delivery vehicles for treating pregnancy-related disorders. It will also examine how specific particle compositions and surface functionalities may improve particle biocompatibility and, thus, outcomes for the pregnant person and fetus. By assessing the safety of exposure for pregnant individuals and their developing fetuses, and providing insight into how toxicity studies can be made more comprehensive and follow ethical and regulatory guidelines, this review will offer researchers promising approaches for advancing nanotechnology in the maternal-fetal health space while prioritizing patient safety.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114026"},"PeriodicalIF":10.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594594","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":"Peptide-based strategies for glioblastoma therapy: From small molecular drugs to delivery vehicles","authors":"Na Song ,&nbsp;Wenmin Xiong ,&nbsp;Jiantao Zhu ,&nbsp;Chao Zhu ,&nbsp;Xiangling Gu ,&nbsp;Zhilin Yu","doi":"10.1016/j.jconrel.2025.114023","DOIUrl":"10.1016/j.jconrel.2025.114023","url":null,"abstract":"<div><div>Glioblastoma (GBM) remains one of the most invasive and treatment-resistant brain tumors. Efficient GBM treatment represents a significant challenge in clinical oncology, thereby underscoring the demand on novel therapeutic strategies. Peptide-based therapeutics have emerged as promising alternatives to conventional drugs, due to their precise targeting capabilities, broad bioactivities, and the prospective to overcome the blood-brain barrier (BBB). This review outlined the diverse functions of peptides in GBM treatment, ranging from targeting agents, therapeutic drugs to delivery vehicles, based on introduction of the applications of peptides towards general cancer therapy. We highlighted the advantages and potential of peptide-based therapeutics from the perspective of various targeted delivering and therapeutic strategies for GBM. While challenges related to peptide stability and bioavailability are critical for clinical usage, peptide-based therapies serving as innovative solutions hold the great potential to enhance GBM treatment efficacy and offer novel avenues for future therapeutic development.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114023"},"PeriodicalIF":10.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594595","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":"Engineered biomembrane-camouflaged nanoparticles: Promising strategies to treat inflammatory skeletal diseases","authors":"Ouzile Chen, Yumeng Zhou, Zihan Xu, Xiaoheng Liu, Demao Zhang, Mingru Bai","doi":"10.1016/j.jconrel.2025.114025","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.114025","url":null,"abstract":"Inflammatory skeletal diseases often result in significant pain and deformities of bone and the surrounding joint tissues, which subsequently cause disorders of immune regulation and calcium‑phosphorus metabolism, greatly impacting patients' quality of life. The precision of drug delivery in inflammatory skeletal diseases is usually limited. Traditional therapies for these conditions require high doses, offer limited efficacy, and frequently lead to side effects that compromise healthy tissues, particularly with prolonged use. Addressing these limitations, biomembrane-camouflaged nanoparticles present a precise and innovative therapeutic strategy with enhanced biocompatibility, targeted delivery to diseased tissues, pharmacokinetic properties, and immune evasion capabilities, improving therapeutic efficacy while reducing adverse effects on healthy tissues, thus adding a vital dimension to inflammatory skeletal disease treatment. By integrating multiple therapeutic functions within a single nanoplatform, these nanostructures introduce transformative strategies that enhance traditional treatment approaches. Here, we provide a comprehensive overview of the latest advancements in the biogenesis, preparation, and functional properties of nanoparticles camouflaged by biomembranes - cell membranes, - extracellular vesicles (EVs), and - liposomes and explore their potential when combined with nanotechnology. Further, we detail biomembrane-camouflaged nanoparticles for inflammatory skeletal disease treatment, examining their applications in osteoarthritis (OA), rheumatoid arthritis (RA), osteomyelitis, osteolysis, and periodontitis. It highlights key advances in immunogenicity reduction, targeted drug delivery, and immune modulation for the effective management of inflammatory skeletal diseases.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"21 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594603","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":"Outside Back Cover","authors":"","doi":"10.1016/S0168-3659(25)00636-4","DOIUrl":"10.1016/S0168-3659(25)00636-4","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"384 ","pages":"Article 114015"},"PeriodicalIF":10.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587983","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":"Transfersome enhances nail penetration of antifungal drug and photosensitizer for chemo-photodynamic therapy of onychomycosis in a novel rat model","authors":"Yiyang Li ,&nbsp;Yannan Qin ,&nbsp;Yi Liu ,&nbsp;Bo Yuan ,&nbsp;Zhirong Zhao ,&nbsp;Jingyuan Wang ,&nbsp;Yanhong Ji ,&nbsp;Shuai Mao ,&nbsp;Feng Ye ,&nbsp;Chengcheng Liu ,&nbsp;Chuanbin Mao","doi":"10.1016/j.jconrel.2025.114029","DOIUrl":"10.1016/j.jconrel.2025.114029","url":null,"abstract":"<div><div>Onychomycosis is a prevalent nail infection caused by fungi, presenting significant treatment challenges due to poor drug penetration and high recurrence rates. Current treatments, including oral and topical antifungals, often have limited efficacy and can lead to resistance. Transfersomes are lipid vesicles that can penetrate skin for transdermal drug delivery. Here, a <u>t</u>ransfersome (termed THT) capable of penetrating nails to deliver a photosensitizer (<u>h</u>ematoporphyrin monomethyl ether, HMME) and an antifungal chemotherapeutic drug (<u>t</u>avaborole) has been developed, achieving a chemo-photodynamic synergistic treatment of onychomycosis. The optimized THT was prepared using a combination of soy lecithin, sodium deoxycholate, and cholesterol in an 8: 4: 0.5 ratio, with a particle size of 200 nm and a 30 % alcohol-water solvent system. This formulation significantly enhanced nail penetration, with the concentration of HMME reaching 330 times higher than that in phosphate-buffered saline. Moreover, THT showed potent fungicidal activity, reducing the survival of <em>Trichophyton rubrum</em> microconidia to as low as 3.24 % under light irradiation, and achieving approximately 90 % treatment efficacy in the <em>ex vivo</em> model. In addition to <em>in vitro</em> and <em>ex vivo</em> verification, an innovative rat onychomycosis model was established to confirm its superior therapeutic efficacy <em>in vivo</em>, with cure rates around 90 % and a significant reduction in fungal hyphae and spores. It is accumulated around and deformed to enter the physiological pores of the nail plate, effectively penetrating to deeper layers at the nail bed. THT, with its high nail penetration efficiency and potent synergistic antifungal activity, represents a promising topical treatment for onychomycosis.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114029"},"PeriodicalIF":10.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594596","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}