Journal of Controlled Release最新文献

{"title":"Melittin-incorporated nanomedicines for enhanced cancer immunotherapy","authors":"","doi":"10.1016/j.jconrel.2024.08.047","DOIUrl":"10.1016/j.jconrel.2024.08.047","url":null,"abstract":"<div><p>Immunotherapy is a rapidly developing and effective strategy for cancer therapy. Among various immunotherapy approaches, peptides have garnered significant attention due to their potent immunomodulatory effects. In particular, melittin emerged as a promising candidate to enhance cancer immunotherapy by inducing immunogenic cell death, promoting the maturation of antigen-presenting cells, activating T cells, enhancing the infiltration and cytotoxicity of effector lymphocytes, and modulating macrophage phenotypes for relieving immunosuppression. However, the clinical application of melittin is limited by poor targeting and systemic toxicity. To overcome these challenges, melittin has been incorporated into biomaterials and related nanotechnologies, resulting in extended circulation time <em>in vivo</em>, improved targeting, reduced adverse effects, and enhanced anti-cancer immunological action. This review provides an in-depth analysis of the immunomodulatory effects of melittin-incorporated nanomedicines and examines their development and challenges for clinical cancer immunotherapy.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107925","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":"Biofilm-camouflaged Prussian blue synergistic mitochondrial mass enhancement for Alzheimer's disease based on Cu2+ chelation and photothermal therapy","authors":"","doi":"10.1016/j.jconrel.2024.09.009","DOIUrl":"10.1016/j.jconrel.2024.09.009","url":null,"abstract":"<div><p>Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive and memory impairment. Metal ion imbalance and Mitochondrial dysfunction, leading to abnormal aggregation of β-amyloid protein (Aβ), are key factors in the pathogenesis of AD. Therefore, we designed a composite nanometer system of red blood cell (RBC) membranes-encapsulated Prussian blue nanoparticles (PB/RBC). Prussian blue nanoparticles (PBNPs) can chelate Cu²⁺ and reduce reactive oxygen species (ROS). The RBC membranes are a kind of natural long-lasting circulating carrier. At the same time, through NIR irradiation, the excellent photothermal ability of PBNPs can also temporarily open the blood-brain barrier (BBB), enhance the transmission efficiency of PB/RBC across the BBB, and depolymerize the formed Aβ deposits, thereby achieving the optimal therapeutic effect. In vitro and in vivo studies demonstrated that PB/RBC could inhibit Cu²⁺-induced Aβ monomers aggregation, eliminate the deposition of Aβ plaques, improve the quality of mitochondria, restore the phagocytic function of microglia, alleviate neuroinflammation in APP/PS1 mice, and repair memory damage. In conclusion, our biofilm-camouflaged nano-delivery system provides significant neuroprotection by inhibiting Cu²⁺-induced Aβ monomers aggregation, photothermally depolymerizing Aβ fibrils and reducing the level of ROS, thus effectively ameliorating and treating AD.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154219","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 integrated long-acting implant of clinical safe cells, drug and biomaterials effectively promotes spinal cord repair and restores motor functions","authors":"","doi":"10.1016/j.jconrel.2024.09.010","DOIUrl":"10.1016/j.jconrel.2024.09.010","url":null,"abstract":"<div><p>Spinal cord injury (SCI) is incurable and raises growing concerns. The main barrier to nerve repair is the complicated inhibitory microenvironment, where single-targeted strategies are largely frustrated. Despite the progress in combinatory therapeutic systems, the development and translation of effective therapies remain a challenge with extremely limited clinical materials. In this study, mesenchymal stem cells are transplanted in combination with sustained release of methylprednisolone through delivery in one composite matrix of a microsphere-enveloped adhesive hydrogel. All the materials used, including the stem cells, drug, and the matrix polymers gelatin and hyaluronan, are clinically approved. The therapeutic effects and safety issues are evaluated on rat and canine SCI models. The implantation significantly promotes functional restoration and nerve repair in a severe long-span rat spinal cord transection model. Distant spinal cord segments and the urinary system are effectively protected against pathologic damage. Moreover, the local sustained drug delivery mitigates the inflammatory microenvironment when overcoming the clinical issue of systemic side effects. The study presents an innovative strategy to achieve safe and efficient combinatory treatment of SCI.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154218","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":"Immunomodulatory metal-based biomaterials for cancer immunotherapy","authors":"","doi":"10.1016/j.jconrel.2024.09.008","DOIUrl":"10.1016/j.jconrel.2024.09.008","url":null,"abstract":"<div><p>Cancer immunotherapy, as an emerging cancer treatment approach, harnesses the patient's own immune system to effectively prevent tumor recurrence or metastasis. However, its clinical application has been significantly hindered by relatively low immune response rates. In recent years, metal-based biomaterials have been extensively studied as effective immunomodulators and potential tools for enhancing anti-tumor immune responses, enabling the reversal of immune suppression without inducing toxic side effects. This review introduces the classification of bioactive metal elements and summarizes their immune regulatory mechanisms. In addition, we discuss the immunomodulatory roles of biomaterials constructed from various metals, including aluminum, manganese, gold, calcium, zinc, iron, magnesium, and copper. More importantly, a systematic overview of their applications in enhancing immunotherapy is provided. Finally, the prospects and challenges of metal-based biomaterials with immunomodulatory functions in cancer immunotherapy are outlined.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142173557","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":"Advancements of engineered live oncolytic biotherapeutics (microbe/virus/cells): Preclinical research and clinical progress","authors":"","doi":"10.1016/j.jconrel.2024.09.006","DOIUrl":"10.1016/j.jconrel.2024.09.006","url":null,"abstract":"<div><p>The proven efficacy of immunotherapy in fighting tumors has been firmly established, heralding a new era in harnessing both the innate and adaptive immune systems for cancer treatment. Despite its promise, challenges such as inefficient delivery, insufficient tumor penetration, and considerable potential toxicity of immunomodulatory agents have impeded the advancement of immunotherapies. Recent endeavors in the realm of tumor prophylaxis and management have highlighted the use of living biological entities, including bacteria, oncolytic viruses, and immune cells, as a vanguard for an innovative class of live biotherapeutic products (LBPs). These LBPs are gaining recognition for their inherent ability to target tumors. However, these LBPs must contend with significant barriers, including robust immune clearance mechanisms, cytotoxicity and other in vivo adverse effects. Priority must be placed on enhancing their safety and therapeutic indices. This review consolidates the latest preclinical research and clinical progress pertaining to the exploitation of engineered biologics, spanning bacteria, oncolytic viruses, immune cells, and summarizes their integration with combination therapies aimed at circumventing current clinical impasses. Additionally, the prospective utilities and inherent challenges of the biotherapeutics are deliberated, with the objective of accelerating their clinical application in the foreseeable future.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination non-targeted and sGRP78-targeted nanoparticle drug delivery outperforms either component to treat metastatic ovarian cancer.","authors":"Jenna N Sjoerdsma,Emily Bromley,Jaeho Shin,Tyvette Hilliard,Yueying Liu,Caitlin Horgan,Gyoyeon Hwang,Michael Bektas,David Omstead,Tanyel Kiziltepe,M Sharon Stack,Basar Bilgicer","doi":"10.1016/j.jconrel.2024.09.014","DOIUrl":"https://doi.org/10.1016/j.jconrel.2024.09.014","url":null,"abstract":"Metastatic ovarian cancer (MOC) is highly deadly, due in part to the limited efficacy of standard-of-care chemotherapies to metastatic tumors and non-adherent cancer cells. Here, we demonstrated the effectiveness of a combination therapy of GRP78-targeted (TNPGRP78pep) and non-targeted (NP) nanoparticles to deliver a novel DM1-prodrug to MOC in a syngeneic mouse model. Cell surface-GRP78 is overexpressed in MOC, making GRP78 an optimal target for selective delivery of nanoparticles to MOC. The NP + TNPGRP78pep combination treatment reduced tumor burden by 15-fold, compared to untreated control. Increased T cell and macrophage levels in treated groups also suggested antitumor immune system involvement. The NP and TNPGRP78pep components functioned synergistically through two proposed mechanisms of action. The TNPGRP78pep targeted non-adherent cancer cells in the peritoneal cavity, preventing the formation of new solid tumors, while the NP passively targeted existing solid tumor sites, providing a sustained release of the drug to the tumor microenvironment.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233459","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":"Cocrystal engineering for sustained release of dicamba: Mitigating secondary drift and reducing leaching","authors":"","doi":"10.1016/j.jconrel.2024.09.005","DOIUrl":"10.1016/j.jconrel.2024.09.005","url":null,"abstract":"<div><p>The off-target effects of herbicides present significant challenges in agricultural practices, posing serious threats to both ecological systems and human health. Dicamba, one of the most widely used herbicides, is particularly problematic due to its high volatility and water solubility, which can lead to rapid environmental dispersal, non-target toxicity, and groundwater contamination. To mitigate these issues, we synthesized a novel cocrystal of dicamba and phenazine (DCB-PHE cocrystal) through a combination of theoretical prediction and mechanochemical screening. The DCB-PHE cocrystal was characterized using single-crystal and powder X-ray diffraction, Fourier-transform infrared spectroscopy (FT-IR), and thermal analysis. Compared to pure dicamba, the DCB-PHE cocrystal exhibited a substantial reduction in volatility by 59 % and a decrease in equilibrium solubility by up to 5.4 times across various temperatures (15 °C, 25 °C, 35 °C). Additionally, the dissolution rates were significantly lowered by over 94 %. Leaching experiments demonstrated that the DCB-PHE cocrystal reduced total leachate by 4.9 % and delayed percolation. In greenhouse trials, the DCB-PHE cocrystal caused less damage to exposed soy plants and enhanced herbicidal activity against target weeds, with fresh weight reduction of chicory and ryegrass by 32 % and 28 %, respectively, at the highest dosage. Furthermore, safety assays confirmed that the DCB-PHE cocrystal's safety profile was comparable to that of dicamba in terms of its impact on wheat, and it did not exhibit increased genotoxicity to broad beans. These findings suggest that the DCB-PHE cocrystal is a promising candidate for reducing the environmental impacts of dicamba while maintaining its herbicidal efficacy.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154220","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":"Rational design of a poly-L-glutamic acid-based combination conjugate for hormone-responsive breast cancer treatment","authors":"","doi":"10.1016/j.jconrel.2024.09.002","DOIUrl":"10.1016/j.jconrel.2024.09.002","url":null,"abstract":"<div><p>Breast cancer represents the most prevalent tumor type worldwide, with hormone-responsive breast cancer the most common subtype. Despite the effectiveness of endocrine therapy, advanced disease forms represent an unmet clinical need. While drug combination therapies remain promising, differences in pharmacokinetic profiles result in suboptimal ratios of free drugs reaching tumors. We identified a synergistic combination of bisdemethoxycurcumin and exemestane through drug screening and rationally designed <em>star</em>-shaped poly-L-glutamic acid-based combination conjugates carrying these drugs conjugated through pH-responsive linkers for hormone-responsive breast cancer treatment. We synthesized/characterized single and combination conjugates with synergistic drug ratios/loadings. Physicochemical characterization/drug release kinetics studies suggested that lower drug loading prompted a less compact conjugate conformation that supported optimal release. Screening in monolayer and spheroid breast cancer cell cultures revealed that combination conjugates possessed enhanced cytotoxicity/synergism compared to physical mixtures of single-drug conjugates/free drugs; moreover, a combination conjugate with the lowest drug loading outperformed remaining conjugates. This candidate inhibited proliferation-associated signaling, reduced inflammatory chemokine/exosome levels, and promoted autophagy in spheroids; furthermore, it outperformed a physical mixture of single-drug conjugates/free drugs regarding cytotoxicity in patient-derived breast cancer organoids. Our findings highlight the importance of rational design and advanced in vitro models for the selection of polypeptide-based combination conjugates.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168365924006047/pdfft?md5=6462850149337601a730fb9d392d0810&pid=1-s2.0-S0168365924006047-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural pachypodol integrated, lung targeted and inhaled lipid nanomedicine ameliorates acute lung injury via anti-inflammation and repairing lung barrier.","authors":"Zhi-Chao Sun,Ran Liao,Caihong Xian,Ran Lin,Liying Wang,Yifei Fang,Zhongde Zhang,Yuntao Liu,Jun Wu","doi":"10.1016/j.jconrel.2024.09.013","DOIUrl":"https://doi.org/10.1016/j.jconrel.2024.09.013","url":null,"abstract":"Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a high-mortality disease caused by multiple disorders such as COVID-19, influenza, and sepsis. Current therapies mainly rely on the inhalation of nitric oxide or injection of pharmaceutical drugs (e.g., glucocorticoids); however, their toxicity, side effects, or administration routes limit their clinical application. In this study, pachypodol (Pac), a hydrophobic flavonol with anti-inflammatory effects, was extracted from Pogostemon cablin Benth and intercalated in liposomes (Pac@liposome, Pac-lipo) to improve its solubility, biodistribution, and bioavailability, aiming at enhanced ALI/ARDS therapy. Nanosized Pac-lipo was confirmed to have stable physical properties, good biodistribution, and reliable biocompatibility. In vitro tests proved that Pac-lipo has anti-inflammatory property and protective effects on endothelial and epithelial barriers in lipopolysaccharide (LPS)-induced macrophages and endothelial cells, respectively. Further, the roles of Pac-lipo were validated on treating LPS-induced ALI in mice. Pac-lipo showed better effects than did Pac alone on relieving ALI phenotypes: It significantly attenuated lung index, improved pulmonary functions, inhibited cytokine expression such as TNF-α, IL-6, IL-1β, and iNOS in lung tissues, alleviated lung injury shown by HE staining, reduced protein content and total cell number in bronchoalveolar lavage fluid, and repaired lung epithelial and vascular endothelial barriers. As regards the underlying mechanisms, RNA sequencing results showed that the effects of the drugs were associated with numerous immune- and inflammation-related signaling pathways. Molecular docking and western blotting demonstrated that Pac-lipo inhibited the activation of the TLR4-MyD88-NF-κB/MAPK signaling pathway. Taken together, for the first time, our new drug (Pac-lipo) ameliorates ALI via inhibition of TLR4-MyD88-NF-κB/MAPK pathway-mediated inflammation and disruption of lung barrier. These findings may provide a promising strategy for ALI treatment in the clinic.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231341","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":"Advances in DNA nanotechnology for chronic wound management: Innovative functional nucleic acid nanostructures for overcoming key challenges","authors":"","doi":"10.1016/j.jconrel.2024.09.004","DOIUrl":"10.1016/j.jconrel.2024.09.004","url":null,"abstract":"<div><p>Chronic wound management is affected by three primary challenges: bacterial infection, oxidative stress and inflammation, and impaired regenerative capacity. Conventional treatment methods typically fail to deliver optimal outcomes, thus highlighting the urgency to develop innovative materials that can address these issues and improve efficacy. Recent advances in DNA nanotechnology have garnered significant interest, particularly in the field of functional nucleic acid (FNA) nanomaterials, owing to their exceptional biocompatibility, programmability, and therapeutic potential. Among them, FNAs with unique nanostructures have garnered considerable attention. First, they inherit the biological properties of FNAs, including biocompatibility, reactive oxygen species (ROS)-scavenging capabilities, and modulation of cellular functions. Second, based on a precise design, these nanostructures exhibit superior physical properties, stability, and cellular uptake. Third, by leveraging the programmability of DNA strands, FNA nanostructures can be customized to accommodate therapeutic nucleic acids, peptides, and small-molecule drugs, thereby enabling a stable and controlled drug delivery system. These unique characteristics enable the use of FNA nanostructures to effectively address the major challenges in chronic wound management. This review focuses on various FNA nanostructures, including tetrahedral framework nucleic acids (tFNAs), DNA hydrogels, DNA origami, and rolling-circle amplification (RCA) DNA assembly. Additionally, a summary of recent advancements in their design and application for chronic wound management as well as insights for future research in this field are provided.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145738","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}