Journal of Controlled Release最新文献

{"title":"Cell membrane derived biomimetic nanomedicine for precision delivery of traditional Chinese medicine in cancer therapy","authors":"Hang Xiao ,&nbsp;Faisal Raza ,&nbsp;Kunwei Li,&nbsp;Jinpu Song,&nbsp;Hajra Zafar,&nbsp;Shiqi Yang,&nbsp;Jing Su,&nbsp;Mingfeng Qiu","doi":"10.1016/j.jconrel.2025.113829","DOIUrl":"10.1016/j.jconrel.2025.113829","url":null,"abstract":"<div><div>The rapidly developing modern nanotechnology has brought new vitality to the application of traditional Chinese medicine (TCM), improving the pharmacokinetics and bioavailability of unmodified natural drugs. However, synthetic materials inevitably introduce incompatibilities. This has led to focusing on biomimetic drug delivery systems (DDS) based on biologically derived cell membranes. This “top-down” approach to nanomedicine preparation is simple and effective, as the inherited cell membranes and cell surface substances can mimic nature when delivering drugs back into the body, interacting similarly to the source cells at the biological interface. The concept of biologically derived TCM and biomimetic membranes aligns well with nature, the human body, and medicine, thereby enhancing the in vivo compatibility of TCM. This review focused on the recent progress using biomimetic membranes for TCM in cancer therapy, emphasizing the effective integration of biomimetic nanomedicine and TCM in applications such as cancer diagnosis, imaging, precision treatment, and immunotherapy. The review also provided potential suggestions on the challenges and prospects in this field.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113829"},"PeriodicalIF":10.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931299","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":"Biomimetic liposomal nanovesicles remodel the tumor immune microenvironment to augment sono-immunotherapy","authors":"Hongxin Zhao ,&nbsp;Fangxue Du ,&nbsp;Jianbo Huang,&nbsp;Ruiqian Guo,&nbsp;Ziyan Feng,&nbsp;Ziyao Wang,&nbsp;Li Qiu","doi":"10.1016/j.jconrel.2025.113830","DOIUrl":"10.1016/j.jconrel.2025.113830","url":null,"abstract":"<div><div>Sonodynamic therapy (SDT)-mediated immunogenic cell death and immune checkpoint blockade offer new opportunities for tumor treatment. However, challenges including immunosuppression, hypoxic tumor microenvironments, and inadequate drug delivery hinder therapeutic efficacy. Therefore, we developed a multifunctional biomimetic liposome microbubble named H-R@Lip@M, which is coated with melanoma cell membranes, contains perfluoropentane as its core, and is loaded with the sonosensitizer hematoporphyrin monomethyl ether and the immune adjuvant resiquimod. The targeting properties of melanoma cell membranes enable effective accumulation of nanoparticles (NPs) at tumor sites. Equipped with ultrasonic/photoacoustic imaging capabilities, these NPs allow precise control over the release of drugs and oxygen upon ultrasound stimulation. In vitro and in vivo results consistently showed that the NPs enhanced anti-tumor efficacy, halting primary tumor progression and preventing lung metastasis. Moreover, SDT increased reactive oxygen species levels within tumors, preferentially inducing apoptosis while maximizing immunogenic cell death. When combined with PD-L1 blockade, this synergy promotes dendritic cell maturation and alters various immune populations, boosting T-cell infiltration while enhancing M1 macrophage polarization and reducing regulatory T-cell presence. In summary, the proposed combination has the potential to synergistically enhance the efficacy of sono-immunotherapy by remodeling the immunosuppressive microenvironment, providing valuable insights for addressing challenges associated with SDT-based cancer therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113830"},"PeriodicalIF":10.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932572","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":"Multivalent assembly of nucleolin-targeted F3 peptide potentiates TRAIL's tumor penetration and antitumor effects","authors":"Ze Tao ,&nbsp;Yingying Li ,&nbsp;Yunchuan Huang ,&nbsp;Liqiang Hu ,&nbsp;Shisheng Wang ,&nbsp;Lin Wan ,&nbsp;Tianshan She ,&nbsp;Qiuxiao Shi ,&nbsp;Sifen Lu ,&nbsp;Xinyue Wang ,&nbsp;Yi Zhong ,&nbsp;Tao Su ,&nbsp;Xinyuan Wang ,&nbsp;Dan Long ,&nbsp;Yan Li ,&nbsp;Jie Zhang ,&nbsp;Lijun Wang ,&nbsp;Tingting Long ,&nbsp;Hong Zhu ,&nbsp;Xiaofeng Lu ,&nbsp;Hao Yang","doi":"10.1016/j.jconrel.2025.113835","DOIUrl":"10.1016/j.jconrel.2025.113835","url":null,"abstract":"<div><div>Tumor-targeting drug delivery holds great promise for cancer treatment but faces significant challenges in penetrating solid tumors to achieve optimal therapeutic efficacy. By harnessing the natural tissue-penetration effect conferred by the CendR motif, we identified that the nucleolin (NCL)-targeted peptide F3 possesses tumor-penetrating capabilities. Co-administration of F3 with doxorubicin and the apoptosis-inducing protein TRAIL enhanced effective tumor penetration and improved antitumor activity. Taking advantage of TRAIL's natural self-trimerization, we developed a novel fusion protein, F3-TRAIL. This design enabled the trivalent assembly of F3 when fused with TRAIL, significantly enhancing its binding to NCL-positive tumor endothelial and parenchymal cells, resulting in deeper tumor penetration and superior antitumor effects compared to TRAIL alone. Mechanistic studies revealed that the multivalent F3-enhanced engagement with tumor cells potentiated TRAIL to trigger death receptor-dependent apoptosis signaling, even in TRAIL-resistant tumor cells. Building on this success, we constructed F3-HexaTR using the SpyCatcher/SpyTag superglue ligation system to generate a hexameric TRAIL, further amplifying cytotoxicity and antitumor efficacy. Combined analysis of data from TCGA and GTEx revealed significantly elevated NCL expression across 18 solid tumor types, underscoring the clinical potential of F3-directed targeted therapy. These findings highlight that F3-mediated NCL targeting is an effective strategy to overcome tumor penetration barriers, particularly for protein drug delivery. This multivalent assembly approach represents an innovative avenue for enhancing the therapeutic efficacy of various agents in the treatment of solid tumors.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113835"},"PeriodicalIF":10.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931025","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-action membrane-chimeric liposomes with self-reinforcing targeting for acute lung injury treatment","authors":"Wenjing Bai ,&nbsp;Shuang Chen ,&nbsp;Tingting Liu ,&nbsp;Xian Tang ,&nbsp;Lin Xiong ,&nbsp;Man Li ,&nbsp;Rong Guo ,&nbsp;Qin He","doi":"10.1016/j.jconrel.2025.113820","DOIUrl":"10.1016/j.jconrel.2025.113820","url":null,"abstract":"<div><div>Acute lung injury (ALI) is a common acute and critical syndrome with high mortality. The uncontrollable feedback loop of inflammation is the primary cause of death in patients with ALI. Therefore, targeting the inflammatory site and breaking the inflammatory loop are key strategies for ALI treatment. Our work developed a myeloid cell membrane-chimeric liposome containing dexamethasone (DEX) and leukocyte adhesin-1 (LA-1), abbreviated as ML/LA@DEX NPs. During the preparation of ML/LA@DEX NPs, LA-1 could activate CD11b on the myeloid cell membrane, thereby improving the binding ability of ML/LA@DEX NPs to ICAM-1 on endothelial cells in pulmonary inflammatory lesions, and achieving self-reinforcing targeting of ALI. ML/LA@DEX NPs accumulated at the inflammatory lesions would competitively occupy the binding site of neutrophils to reduce their recruitment. Meanwhile, ML/LA@DEX NPs would release DEX to inhibit the cytokine storm. Through this two-pronged approach, ML/LA@DEX NPs effectively broke the positive feedback loop of inflammation and showed significant therapeutic effects on ALI, providing a new strategy for ALI treatment.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113820"},"PeriodicalIF":10.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926586","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":"Animal vaccine revolution: Nanoparticle adjuvants open the future of vaccinology","authors":"Shangen Xu ,&nbsp;Chenxi Sun ,&nbsp;Tianyu Qian ,&nbsp;Yao Chen ,&nbsp;Xinhui Dong ,&nbsp;Afei Wang ,&nbsp;Qihong Zhang ,&nbsp;Yile Ji ,&nbsp;Zheng Jin ,&nbsp;Chibo Liu ,&nbsp;Kai Zhao","doi":"10.1016/j.jconrel.2025.113827","DOIUrl":"10.1016/j.jconrel.2025.113827","url":null,"abstract":"<div><div>In recent years, the rapid development of nanoparticle adjuvants has greatly facilitated the treatment and prevention of infectious diseases in humans and animals. The remarkable success of mRNA nanovaccines against SARS-CoV-2 has accelerated the advancement of nanoparticle adjuvant technologies in the era of precision medicine. Significant progress has been made in researching nanovaccines for major animal infectious diseases, such as porcine epidemic diarrhea, avian influenza, porcine reproductive and respiratory syndrome, bovine viral diarrhea, foot-and-mouth disease, African swine fever, and Newcastle disease. This article reviews the nanoparticle adjuvants under investigation for animal use, emphasizing their diverse mechanisms of action and immunological properties, and analyzes the physicochemical factors influencing their immune-enhancing effects. On this basis, we discuss future prospects and key challenges that need to be addressed, aiming to provide valuable references for the development of novel animal vaccine adjuvants.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113827"},"PeriodicalIF":10.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931071","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":"Are lateral lipid-phase diffusion coefficients pertinent to dermal absorption?","authors":"Junxi Wang, Arne Nägel, Gerald B. Kasting, Johannes M. Nitsche","doi":"10.1016/j.jconrel.2025.113773","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113773","url":null,"abstract":"The skin's outer barrier layer, the stratum corneum (SC), is comprised of keratin-rich corneocytes, connected by proteinaceous corneodesmosomes and separated by nonpolar, lamellar lipids. The lipids are inherently anisotropic due to their lamellar organization. There is growing acceptance that this structural anisotropy carries over into transport properties including diffusive mass transport, which is consequently characterized by two diffusion coefficients, &lt;span&gt;&lt;span style=\"\"&gt;&lt;math&gt;&lt;msubsup is=\"true\"&gt;&lt;mi is=\"true\"&gt;D&lt;/mi&gt;&lt;mo is=\"true\"&gt;∥&lt;/mo&gt;&lt;mi is=\"true\"&gt;lip&lt;/mi&gt;&lt;/msubsup&gt;&lt;/math&gt;&lt;/span&gt;&lt;span style=\"font-size: 90%; display: inline-block;\" tabindex=\"0\"&gt;&lt;svg focusable=\"false\" height=\"3.817ex\" role=\"img\" style=\"vertical-align: -1.389ex;\" viewbox=\"0 -1045.3 1715.9 1643.4\" width=\"3.985ex\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g fill=\"currentColor\" stroke=\"currentColor\" stroke-width=\"0\" transform=\"matrix(1 0 0 -1 0 0)\"&gt;&lt;g is=\"true\"&gt;&lt;g is=\"true\"&gt;&lt;use xlink:href=\"#MJMATHI-44\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g is=\"true\" transform=\"translate(828,482)\"&gt;&lt;use transform=\"scale(0.707)\" xlink:href=\"#MJMAIN-6C\"&gt;&lt;/use&gt;&lt;use transform=\"scale(0.707)\" x=\"278\" xlink:href=\"#MJMAIN-69\" y=\"0\"&gt;&lt;/use&gt;&lt;use transform=\"scale(0.707)\" x=\"557\" xlink:href=\"#MJMAIN-70\" y=\"0\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g is=\"true\" transform=\"translate(828,-367)\"&gt;&lt;use transform=\"scale(0.707)\" xlink:href=\"#MJMAIN-2225\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;/g&gt;&lt;/g&gt;&lt;/svg&gt;&lt;/span&gt;&lt;script type=\"math/mml\"&gt;&lt;math&gt;&lt;msubsup is=\"true\"&gt;&lt;mi is=\"true\"&gt;D&lt;/mi&gt;&lt;mo is=\"true\"&gt;∥&lt;/mo&gt;&lt;mi is=\"true\"&gt;lip&lt;/mi&gt;&lt;/msubsup&gt;&lt;/math&gt;&lt;/script&gt;&lt;/span&gt; for lateral diffusion along the lipid lamellae and &lt;span&gt;&lt;span style=\"\"&gt;&lt;math&gt;&lt;msubsup is=\"true\"&gt;&lt;mi is=\"true\"&gt;D&lt;/mi&gt;&lt;mo is=\"true\"&gt;⊥&lt;/mo&gt;&lt;mi is=\"true\"&gt;lip&lt;/mi&gt;&lt;/msubsup&gt;&lt;/math&gt;&lt;/span&gt;&lt;span style=\"font-size: 90%; display: inline-block;\" tabindex=\"0\"&gt;&lt;svg focusable=\"false\" height=\"3.355ex\" role=\"img\" style=\"vertical-align: -0.928ex;\" viewbox=\"0 -1045.3 1715.9 1444.7\" width=\"3.985ex\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g fill=\"currentColor\" stroke=\"currentColor\" stroke-width=\"0\" transform=\"matrix(1 0 0 -1 0 0)\"&gt;&lt;g is=\"true\"&gt;&lt;g is=\"true\"&gt;&lt;use xlink:href=\"#MJMATHI-44\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g is=\"true\" transform=\"translate(828,482)\"&gt;&lt;use transform=\"scale(0.707)\" xlink:href=\"#MJMAIN-6C\"&gt;&lt;/use&gt;&lt;use transform=\"scale(0.707)\" x=\"278\" xlink:href=\"#MJMAIN-69\" y=\"0\"&gt;&lt;/use&gt;&lt;use transform=\"scale(0.707)\" x=\"557\" xlink:href=\"#MJMAIN-70\" y=\"0\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g is=\"true\" transform=\"translate(828,-310)\"&gt;&lt;use transform=\"scale(0.707)\" xlink:href=\"#MJMAIN-22A5\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;/g&gt;&lt;/g&gt;&lt;/svg&gt;&lt;/span&gt;&lt;script type=\"math/mml\"&gt;&lt;math&gt;&lt;msubsup is=\"true\"&gt;&lt;mi is=\"true\"&gt;D&lt;/mi&gt;&lt;mo is=\"true\"&gt;⊥&lt;/mo&gt;&lt;mi is=\"true\"&gt;lip&lt;/mi&gt;&lt;/msubsup&gt;&lt;/math&gt;&lt;/script&gt;&lt;/span&gt; for transverse diffusion across them. Many microscopic models of SC transport have focused on &lt;span&gt;&lt;span style=\"\"&gt;&lt;math&gt;&lt;msubsup is=\"true\"&gt;&lt;mi is=\"true\"&gt;D&lt;/mi&gt;&lt;mo is=\"true\"&gt;∥&lt;/mo&gt;&lt;mi is=\"true\"&gt;lip&lt;/mi&gt;&lt;/msubsup&gt;&lt;/math&gt;&lt;/span&gt;&lt;span style=\"font-size: 90%; display: inline-block;\" tabindex=\"0\"&gt;&lt;svg focusable=\"false\" height=\"3.817ex\" role=\"img\" st","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"25 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926588","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":"Integrity of polymeric micelles regulates bioavailability of cyclosporine A: A FRET-based analysis during oral delivery","authors":"Haihan Sun ,&nbsp;Jiansong Zhao ,&nbsp;Boyuan Liu ,&nbsp;Jingxin Gou ,&nbsp;Haibing He ,&nbsp;Yu Zhang ,&nbsp;Tian Yin ,&nbsp;Xiangqun Jin ,&nbsp;Xing Tang","doi":"10.1016/j.jconrel.2025.113831","DOIUrl":"10.1016/j.jconrel.2025.113831","url":null,"abstract":"<div><div>This study comprehensively investigated the effect of structural integrity on the oral delivery efficacy of mPEG-<em>b</em>-PCL polymeric micelles (PMs) using fluorescence resonance energy transfer (FRET) technology. During mucus penetration, the integrity loss of PMs resulted from the “hydration effect” of mucins and the “solubilization effect” of bile salts. Increasing surface PEG density or decreasing particle size &lt;50 nm resisted the “hydration effect”, while shortening PCL chain or increasing aggregation number alleviated the “solubilization effect”. Fluorescence colocalization studies demonstrated that low surface PEG density and small particle size enhanced the cellular uptake of PMs, but high surface PEG density preserved the intracellular integrity of PMs. Approximately 30 %–60 % of endocytosed PMs were expelled within 4 h, correlating with their cellular uptake efficiency. Transcellular transport results indicated that 5 %–25 % of PMs underwent transcytosis within 4 h, 0.5 %–10 % of initial PMs remained intact. <em>In situ</em> intestine perfusion data confirmed the consistency between the <em>in vitro</em> findings and the actual performance of PMs <em>in vivo</em>. Two types of PMs were selected to encapsulate cyclosporine A (CyA) based on their enhanced integrity and transcytosis efficiency. The PM with a short amphiphilic block and loose structure exhibited comparable <em>in vitro</em> release and <em>in vivo</em> performance to Neoral®, with a C_max of 1356.28 ± 170.01 ng/mL, a T_max of 2 h, and an AUC_0-t of 16,408.92 ± 1166.78 ng/mL*h. However, the PM with a long amphiphilic block and ordered core PCL arrangement exhibited sustained release of CyA both <em>in vitro</em> and <em>in vivo</em>, decreasing CyA accumulation in major organs and improving the oral bioavailability of CyA, with a C_max of 757.07 ± 66.19 ng/mL, a T_max of 9.33 ± 2.31 h, and an AUC_0-t of 21,938.44 ± 2183.59 ng/mL*h.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113831"},"PeriodicalIF":10.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926587","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":"Intracerebral delivery of the ionic liquid form of edaravone via nose-to-brain delivery route for treating cerebral ischemia/reperfusion injury","authors":"Tatsuya Fukuta ,&nbsp;Kotone Yoshimura ,&nbsp;Rikuto Ihara ,&nbsp;Katsuhiko Minoura ,&nbsp;Mayumi Ikeda-Imafuku ,&nbsp;Kazunori Kadota","doi":"10.1016/j.jconrel.2025.113834","DOIUrl":"10.1016/j.jconrel.2025.113834","url":null,"abstract":"<div><div>Nose-to-brain drug delivery via intranasal administration is expected to be a promising route for efficient delivery to the central nervous system (CNS), as it allows for noninvasive and direct delivery of drugs to the CNS by avoiding the blood-brain barrier. However, the delivery efficiency of the administered drugs is still limited owing to poor mucosal epithelium permeation and mucociliary clearance. The use of ionic liquids (ILs) has garnered substantial attention in biomedical engineering for their potential to improve the physicochemical properties of active pharmaceutical ingredients and overcome biological barriers that impede drug delivery to the desired sites. We hypothesized that ILs are promising delivery platforms for achieving efficient permeation through the mucosal epithelium for nose-to-brain delivery. Herein, we newly developed IL forms of edaravone (edaravone-ILs), a clinically used cerebroprotectant, and applied them to nose-to-brain delivery to treat cerebral ischemia/reperfusion (I/R) injury. Through a series of in vitro studies, we found the biocompatible edaravone-IL which exhibits superior antioxidant activity and enhanced water solubility compared to that with native edaravone. Following intranasal administration, edaravone delivery to the brain was significantly more efficient with edaravone-IL than that with the edaravone solution. Moreover, the intranasal administration of edaravone-IL significantly ameliorated cerebral I/R injury in transient middle cerebral artery-occluded rats. These findings suggest that ILs offer a promising way for efficient intracerebral drug delivery via the nose-to-brain route and edaravone-IL could serve as a potential cerebroprotective agent for treating cerebral I/R injury.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113834"},"PeriodicalIF":10.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926584","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":"Reversing the immunosuppressive tumor microenvironment via “Kynurenine starvation therapy” for postsurgical triple-negative breast cancer treatment","authors":"Zengguang Liu ,&nbsp;Jiaxin Yin ,&nbsp;Tianyuan Qiu ,&nbsp;Aijiang Liu ,&nbsp;Yanan Yu ,&nbsp;Shengcai Yang ,&nbsp;Ziling Liu ,&nbsp;Quanshun Li","doi":"10.1016/j.jconrel.2025.113832","DOIUrl":"10.1016/j.jconrel.2025.113832","url":null,"abstract":"<div><div>Immunotherapy is a potential strategy to suppress the postoperative recurrence and metastasis of triple-negative breast cancer (TNBC). However, the excessive accumulation of kynurenine (Kyn) leads to immunosuppressive tumor microenvironment (TME) and impedes immunotherapeutic efficacy. Herein, a two-pronged approach through “Kynurenine Starvation Therapy” is proposed based on the <em>in-situ</em> hydrogel implantation for postsurgical treatment of TNBC. The hydrogel is constructed <em>via</em> Schiff base reaction between oxidized dextran (ODEX) and 8-arm poly(ethylene glycol) amine (8-arm PEG-NH₂), which exhibits excellent biocompatibility and gradual biodegradability. The indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor NLG919 and kynureninase (KYNase) are noncovalently loaded into the hydrogel to prepare NLG919 + KYNase@Gel. The obtained hydrogel can sustainably release NLG919 and KYNase to synergistically deplete Kyn, thereby reversing immunosuppression to enhance the antitumor immunity within TME through “Kynurenine Starvation Therapy”. Moreover, a single implantation of NLG919 + KYNase@Gel not only effectively inhibits the postoperative recurrence and metastasis in 4 T1 tumor-bearing mice, but also restrains the growth in an orthotopic TNBC mouse model. These findings highlight an innovative strategy to reinforce the antitumor immune response for the treatment of postsurgical TNBC.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113832"},"PeriodicalIF":10.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926585","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":"Formulation-optimized oncolytic viruses: Advancing systemic delivery and immune amplification","authors":"Ningye Ma ,&nbsp;Jian Gao ,&nbsp;Xiaoao Pang ,&nbsp;Kexin Wu ,&nbsp;Shihua Yang ,&nbsp;Heng Wei ,&nbsp;Yingying Hao","doi":"10.1016/j.jconrel.2025.113822","DOIUrl":"10.1016/j.jconrel.2025.113822","url":null,"abstract":"<div><div>Cancer is a major global public health challenge. Traditional treatments such as surgery, radiotherapy, and chemotherapy often show limited efficacy, minimal improvements in survival rates, and high recurrence risks. With limited therapeutic options for solid tumors, tumor immunotherapy, which harness the body's immune system, has gained significant attention. Oncolytic viruses (OVs) selectively infect and destroy tumor cells, induce immunogenic cell death (ICD) and stimulate antitumor immune responses. However, current OVs therapies, which are predominantly administered via intratumoral injection, have numerous limitations, including the need for guidance, suboptimal viral spread, extracellular matrix barriers, and immune clearance. These challenges hinder repeated dosing effectiveness and restrict its clinical applicability. Although genetic engineering has improved the tumor selectivity and immune activation of OVs, significant delivery challenges remain. Recently, optimizing pharmaceutical formulations to enhance tumor targeting and viral accumulation has emerged as a key approach to improving OV therapy and expanding clinical applicability. This review highlights the critical role of pharmaceutical formulations in biologics and outlines recent advances in OVs formulations. Specifically, we discuss strategies aimed at enhancing tumor targeting, reducing adverse effects, and promoting antitumor immunity. These strategies significantly enhance OV therapeutic potential and inform novel delivery systems for clinical translation.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"383 ","pages":"Article 113822"},"PeriodicalIF":10.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927107","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}