Journal of Controlled Release最新文献

{"title":"Advances in self-assembling growth factor-mimetic peptides for regenerative medicine.","authors":"Chuhan Yao, Xia Wu, Min Wei, Junfeng Shi","doi":"10.1016/j.jconrel.2026.115334","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115334","url":null,"abstract":"<p><p>Growth factors (GFs) are signaling molecules that play pivotal roles in tissue engineering by regulating essential biological processes such as cell proliferation, differentiation, migration, and survival. Despite their remarkable therapeutic potential, the clinical translation of natural GFs remains hindered by several intrinsic limitations, such as high production costs, poor stability and short half-life in vivo, insufficient targeted delivery and controlled release capabilities. To address these challenges, increasing attention has been directed toward growth factor-mimetic peptides derived from the bioactive domains of natural GFs. In particular, self-assembling GF-mimetic peptides can spontaneously organize into ordered nanostructures under physiological conditions, enabling enhanced stability, multivalent bioactivity, and localized presentation of signaling motifs while partially recapitulating the functions of native GFs. In this review, we systematically summarize the classification, structural characteristics, and biological functions of self-assembling GF-mimetic peptides and discuss recent advances in incorporating single or multiple GF-derived active epitopes into various biomaterial platforms. We further highlight how the synergistic or additive effects of these multifunctional systems contribute to enhanced tissue repair and regeneration. In addition, this review emphasizes current design strategies for constructing GF-mimetic peptides, focusing on the relationship between molecular design, self-assembly behavior, and bioactivity. Finally, we discuss the current challenges and future perspectives for the development of self-assembling GF-mimetic peptide systems in regenerative medicine.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115334"},"PeriodicalIF":12.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891937","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":"Harnessing nature's toolbox: Overcoming complex pulmonary physiological barriers via inhalation of biomimetic nanocarriers.","authors":"Xiaolu Xiao, Yawen Huang, Ziqiao Zhong, Lu Gan, Jun Chen, Shumeng Shen, Zhenhao Li, Xin Pan, Chuanbin Wu, Wenhao Wang, Ying Huang","doi":"10.1016/j.jconrel.2026.115325","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115325","url":null,"abstract":"<p><p>Effective pulmonary drug delivery faces formidable physiological barriers，particularly mucociliary clearance, phagocytosis by alveolar macrophages, and the complex pathological microenvironment. To address these challenges, inhaled biomimetic carriers have emerged as a highly advantageous platform for drug delivery. By leveraging characteristics derived from their biological origins, these carriers inherently possess the capacity to bypass specific pulmonary defense mechanisms, thereby significantly enhancing the efficiency of drug delivery in the treatment of respiratory diseases. This review outlines the physiological barriers in the lungs to highlight the necessity of overcoming them. The following sections focus on the latest research and clinical progress of various inhaled biomimetic delivery vehicles, which will contribute to the strategic development of inhaled drug delivery system platforms and provide insights for achieving precise and effective treatment of respiratory diseases.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115325"},"PeriodicalIF":12.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891856","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":"Synergistic inhibition of exosome secretion and PD-L1 silence via a functional supramolecular lipid nanoparticle to boost antitumor immunity.","authors":"Jiayi Men, Xueyan Zhang, Wenjie Zhang, Xiaomin Gao, Meiqi Cheng, Xinyang Yu, Shaolong Qi","doi":"10.1016/j.jconrel.2026.115331","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115331","url":null,"abstract":"<p><p>The treatment of malignancies remains a formidable challenge, driven by the complex interplay of exosome-mediated metastasis and PD-L1-driven immune evasion. Overcoming these barriers through simultaneous modulation of both pathways represents a critical, yet unmet, need in cancer therapy. To address this, we engineer a supramolecular lipid nanoparticle (LNP) wherein lipid-modified cyclodextrin and oxaliplatin (OxPt-2PA) synergize as both a delivery vector and an immunogenic cell death inducer. Leveraging multiple supramolecular interactions, this platform co-encapsulates the exosome inhibitor Nexinhib20 and small interfering RNA targeting PD-L1 (siPD-L1), orchestrating a multi-pronged attack on tumor progression and immunosuppression. In vivo, this therapeutic strategy markedly enhances dendritic cell maturation, promotes cytotoxic T cell infiltration and significantly suppresses both primary tumor growth and distant metastasis. This work establishes a chemotherapy-induced supramolecular integrated co-delivery platform that simultaneously counteracts metastasis and immunosuppression via \"drug-and-gene\" therapy, offering a promising strategy for the treatment of aggressive cancer.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115331"},"PeriodicalIF":12.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in situ forming thermosensitive hydrogel reprograms the ocular microenvironment for corneal alkali burn repair.","authors":"Pan Long, Fei Han, Yan Wu, Zaiyuan Zhang, Tingrui Zhang, Yuancheng Zhao, Mengshan He, Yonghe Hu, Xilin Li","doi":"10.1016/j.jconrel.2026.115333","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115333","url":null,"abstract":"<p><p>Clinical management of acute corneal alkali burns is limited by tear washout and the failure of monotherapies to break the inflammation-neovascularization cycle. To address this, we developed a thermosensitive hydrogel (PRP/QR@gel) co-loaded with platelet-rich plasma (PRP) and quercetin (QR). The low-viscosity precursor adaptively fills irregular defects and solidifies around ocular surface temperature, establishing a tear-resistant drug depot. Mechanistically, the rapid release of hydrophilic PRP drives ordered corneal remodeling via the PI3K/Akt/mTOR pathway. Concurrently, the sustained release of hydrophobic QR scavenges ROS, suppresses NF-κB-mediated inflammation, and blocks HIF-1α/VEGF-driven pathological neovascularization. In a rabbit alkali burn model, PRP/QR@gel accelerated complete epithelialization within 7 days and reduced clinical opacity scores by 50%. This in situ-forming hydrogel offers a translatable solution for severe ocular chemical injuries.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115333"},"PeriodicalIF":12.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887454","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":"Hybrid PLGA nanoparticles outperform SLNs in intracellular delivery of an anti-inflammatory lipid mediator to skeletal muscle cells.","authors":"Eleonora Maretti, Beatrice Recchia, Arianna Votta, Elena Guarnaccia, Francesca Di Cesare, Giuseppe Cannella, Cecilia Rustichelli, Dror Seliktar, Claudia Fuoco, Cesare Gargioli, Elisabetta Ferraro, Eliana Leo, Susanna Molinari","doi":"10.1016/j.jconrel.2026.115332","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115332","url":null,"abstract":"<p><p>Chronic low-grade inflammation (CLGI) contributes to several skeletal muscle disorders as sarcopenia, still lacking disease-specific therapies. Palmitoylethanolamide (PEA) is a natural anti-inflammatory mediator with proven safety, but its high lipophilicity and poor solubility limit bioavailability and muscle delivery. The intrinsic difficulty of actively targeting skeletal muscle cells further supports the need for biomaterial-based strategies to enhance PEA delivery and therapeutic potential. Here, solid lipid nanoparticles (SLNs) and hybrid polymer-lipid PLGA nanoparticles (hyPLGA) are directly compared to identify a nanocarrier optimized for PEA delivery and bioactivity in skeletal muscle tissue. Both carriers exhibited favorable physicochemical profiles and maintained dimensional features after lyophilization, with PEA-SLNs achieving higher encapsulation efficiency. Despite this, PEA-hyPLGA nanoparticles demonstrated superior functional performance in vitro. In C2C12 myoblasts, both formulations were internalized efficiently, yet PEA-hyPLGA nanoparticles exhibited faster uptake kinetic. Notably, PEA-hyPLGA significantly reduced IL-6 and TNF-α transcript levels, enhanced PPAR-α nuclear localization, and mitigated LPS-induced cytotoxicity more effectively than Native PEA or PEA-SLNs. The efficient internalization of PEA-hyPLGA nanoparticles was also observed in human 3D muscle constructs, where the nanoparticles exhibited the ability to penetrate differentiated myofibers. Their behavior was further validated in vivo, where a prolonged retention of PEA-hyPLGA nanoparticles and their ability to reduce inflammatory markers in mouse skeletal muscle, upon intramuscular injection, was observed. Altogether, these findings indicate that hyPLGA nanoparticles represent a convenient nanostructure platform for PEA delivery and anti-inflammatory function in skeletal muscle, supporting their envisaged use as systemic administered targeted therapy toward translational strategies for sarcopenia.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115332"},"PeriodicalIF":12.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887525","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":"Nitric oxide-entrapping bio-adhesive coacervate foam for multi-target therapy of gastrointestinal infections.","authors":"Jie Wang, Shenyuan Ouyang, Zhouyang Tan, Yiying Jia, Jiarui Li, Yumo Chen, Bingjie Tong, Jiaqi Dai, Minmin Wang, Helin Xu","doi":"10.1016/j.jconrel.2026.115329","DOIUrl":"10.1016/j.jconrel.2026.115329","url":null,"abstract":"<p><p>Bacterial biofilms and persistent inflammation undermine conventional antibiotic therapy for gastrointestinal infections, necessitating integrated therapeutic strategies. Here, we develop a nitric oxide (NO)-entrapping coacervate foam (LA-CHSF-NO) from α-lipoic acid-grafted chitosan and sodium alginate that synergistically combines antimicrobial, antioxidant, anti-inflammatory, and mucosal-healing functions. The foam exhibits robust mechanical properties (storage modulus ∼1184 Pa), shear-thinning injectability, self-healing capacity, and sustained NO release over 4 h, enabling durable mucosal retention. LA-CHSF-NO achieves potent bactericidal and anti-biofilm activity against E. coli, MRSA, and P. aeruginosa (>85% eradication) through synergistic membrane disruption and NO-mediated nitrosative stress. Mechanistically, the foam scavenges ROS, activates the Keap1-Nrf2-HO-1 antioxidant axis, promotes macrophage M2 polarization, and suppresses TNF-α, IL-6, and IL-1β while restoring IL-10. In DSS-induced colitis, LA-CHSF-NO alleviates disease severity, repairs epithelial barrier via upregulating occludin, ZO-1, and claudin-5, restores antioxidant enzymes, and normalizes gut microbiota. Remarkably, in H. pylori-induced gastritis, oral LA-CHSF-NO achieves superior bacterial clearance and mucosal healing versus standard triple therapy. This gas-delivery platform offers a paradigm-shifting approach for combating antibiotic-resistant gastrointestinal infections and chronic inflammatory diseases.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115329"},"PeriodicalIF":12.4,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880638","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":"Self-promoting ferroptosis amplifier based on DKK1 inhibition for metastatic cancer therapy.","authors":"Rong Guo, Yingke Liu, Zhaoru Yin, Shuang Chen, Yunxia Ye, Xuxu Ji, Zhengkun Zhang, Dingxue Wang, Man Li, Ji Liu","doi":"10.1016/j.jconrel.2026.115330","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115330","url":null,"abstract":"<p><p>Ferroptosis therapy holds great potential in metastatic cancer treatment. Whereas, Dickkopf-related protein-1 (DKK1) that highly expressed in various tumors might contribute to low ferroptosis sensitivity of tumor cells, which imposed restrictions on ferroptosis therapy. Our research revealed that DKK1 inhibition could sensitive tumor cells to ferroptosis by obstructing the cystine-GSH-GPX4 axis and the CoQ₁₀-FSP1 axis. Moreover, DKK1 inhibition facilitated dormancy of tumor cells, thereby inhibiting their metastatic proliferation. Encouraged by that, a strategy combining DKK1 inhibition with ferroptosis induction was innovatively proposed for metastatic cancer treatment. And a sulfated hyaluronic acid (SHA)-functionalized liposome co-encapsulating DKK1 inhibitor (Gallocyanine) and ferroptosis inducer (RSL3) was developed for this purpose. The constructed SLip/G+R simultaneously targeted primary tumors, circulating tumor cells and tumor metastases by not only binding to P-selectin/CD44 on tumor cells, but also hitchhiking on activated platelets with tumor cells tendency. Particularly, SLip/G+R increased P-selectin/CD44 on tumor cells through DKK1 inhibition, providing more targets for itself and enhancing the targeting effect in a \"self-promoting\" manner. Due to the self-promoting ferroptosis amplification, SLip/G+R exerted excellent anti-tumor and anti-metastasis efficacy. Overall, this study provided a new idea for efficiently eliminating metastatic tumor cells. It is conducive to promoting the development of ferroptosis therapy, and is of great significance for metastatic cancer treatment.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115330"},"PeriodicalIF":12.4,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880766","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":"Molecular dynamics simulations and experimental analysis of lyotropic liquid crystalline phase behavior and drug release mechanisms.","authors":"Yin Chen, Peizhi Zou, Qian Wang, Xiao Han, Yong Cui, Ye He, Siling Wang, Yikun Gao","doi":"10.1016/j.jconrel.2026.115328","DOIUrl":"10.1016/j.jconrel.2026.115328","url":null,"abstract":"<p><p>Lyotropic liquid crystals (LLCs) are a promising class of self-assembled systems with highly tunable topologies. They offer considerable potential for long-acting drug delivery because of their sustained-release capabilities and facile preparation. However, molecular mechanisms underlying LLC formation and the effects of topology on drug release remain poorly understood. In this study, LLC systems with distinct topologies were constructed using soya phosphatidylcholine and glyceryl dioleate. The release behaviors of three model compounds with different hydrophilicities were systematically investigated through in vitro and in vivo experiments. Additionally, molecular dynamics simulations were employed to visualize the lipid self-assembly and elucidate drug release mechanisms at the molecular level. The results reveal that drug release is synergistically regulated by the LLC structure and intermolecular interactions between drugs and lipids (soya phosphatidylcholine and glyceryl dioleate). Notably, molecular dynamics simulations provide ultramicroscopic insights into LLC formation and drug release mechanisms, complementing experimental observations and offering perspectives that are difficult to achieve using conventional techniques.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115328"},"PeriodicalIF":12.4,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880654","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":"Physicochemical and molecular determinants of lipid migration through multicellular assemblies.","authors":"Hanmant Gaikwad, David Angarita, Natalie Carter, Nina Reichardt, David Siegel, Hanna Mattanovich, Danilo Machado De Melo, Thomas J Anchordoquy, Julio Aguado, Arin Graner, Michael Graner, Irina V Balyasnikova, Dmitri Simberg","doi":"10.1016/j.jconrel.2026.115326","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115326","url":null,"abstract":"<p><p>Efficient movement of lipid molecules across multiple cell layers is a fundamental requirement for lipid-based drug delivery, but the physicochemical and molecular properties that enable this process remain poorly understood. To address this question, we generated a library of lipids with the fluorescent cyanine 3 and cyanine 5 dye headgroups, different tail lengths, and headgroup-tail linkers. We used multicellular 3D breast cancer spheroids to study the lipid penetration into the core (core/periphery ratio) with confocal microscopy. The parent non-lipid dye showed complete penetration into the core of spheroids. Short-chain (C12) lipids with stable linkers were distributed throughout the spheroids and reached the core, whereas long-chain (C18) lipids with stable linkers accumulated predominantly at the periphery. On the other hand, ester-based lipids underwent serum-mediated hydrolysis and the release of low-molecular-weight dye that showed deep spheroid penetration. Increasing the solubility and reducing the aggregation of C18 lipids via co-formulation with DSPE-PEG2000 dramatically enhanced migration and penetration into the core. The same principles are applicable to glioma spheroids, patient-derived glioma spheres, human midbrain organoids, and human patient glioma. Mechanistically, the migration and penetration of lipid molecules through multicellular layers is facilitated by increased lipid solubility and by decreased self-assembly. This work outlines key principles for designing lipid-based probes and therapeutics for effective tumor and tissue distribution.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115326"},"PeriodicalIF":12.4,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880617","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":"Hydrogel-based local delivery of bacteriophages for infection control: a systematic review of in vivo evidence","authors":"Nike Walter,Christoph Brochhausen,Thaqif El Khassawna,Corina Vater,Aaron Teja Bolte,Mohammadali Khan Mirzaei,Ronald Man Yeung Wong,Wing-Hoi Cheung,Christian Heiss,Volker Alt,Anja Lode,Li Deng,Markus Rupp","doi":"10.1016/j.jconrel.2026.115335","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115335","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"12 1","pages":"115335"},"PeriodicalIF":10.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893863","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}