Journal of Controlled Release最新文献

{"title":"Lipid nanoparticle (LNP) mediated mRNA delivery in neurodegenerative diseases","authors":"Seyedeh Ghazal Moosavi, Niloufar Rahiman, Mahmoud Reza Jaafari, Leila Arabi","doi":"10.1016/j.jconrel.2025.113641","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113641","url":null,"abstract":"Neurodegenerative diseases (NDD) are characterized by the progressive loss of neurons and the impairment of cellular functions. Messenger RNA (mRNA) has emerged as a promising therapy for treating NDD, as it can encode missing or dysfunctional proteins and anti-inflammatory cytokines or neuroprotective proteins to halt the progression of these diseases. However, effective mRNA delivery to the central nervous system (CNS) remains a significant challenge due to the limited penetration of the blood-brain barrier (BBB). Lipid nanoparticles (LNPs) offer an efficient solution by encapsulating and protecting mRNA, facilitating transfection and intracellular delivery. This review discusses the pathophysiological mechanisms of neurological disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), Huntington's disease (HD), ischemic stroke, spinal cord injury, and Friedreich's ataxia. Additionally, it explores the potential of LNP-mediated mRNA delivery as a therapeutic strategy for these diseases. Various approaches to overcoming BBB-related challenges and enhancing the delivery and efficacy of mRNA-LNPs are discussed, including non-invasive methods with strong potential for clinical translation. With advancements in artificial intelligence (AI)-guided mRNA and LNP design, targeted delivery, gene editing, and CAR-T cell therapy, mRNA-LNPs could significantly transform the treatment landscape for NDD, paving the way for future clinical applications.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"43 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660549","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":"“Shear force-affinity” double-triggered fixed-point cutting nanoplatform for precise atherosclerosis treatment","authors":"Huijuan Zhang, Yingmei Tian, Yan Ren, Yaning Wang, Chaoqun Wang, Lin Hou","doi":"10.1016/j.jconrel.2025.113633","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113633","url":null,"abstract":"Inflammatory infiltration and lipid metabolism disorder are two main characteristics of atherosclerosis (AS) plaque microenvironment. They interact to form a malignant positive feedback cycle, which aggravates the development of AS disease. Therefore, simultaneous improvement of inflammation and lipid metabolism will provide a significant therapeutic effect on AS. To achieve this goal, we first prepared FCD (Fuc-TK-CD) by grafting β-cyclodextrin (β-CD) to fucoidan (Fuc) <em>via</em> reactive oxygen species (ROS)-responsive sulfhydryl disulfide bond (TK), then loaded resveratrol (Res) through the host-guest interaction. Finally, we coated it on the surface of SeNPs through Se<img alt=\"single bond\" src=\"https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/55/entities/sbnd.gif\" style=\"vertical-align:middle\"/>O bonds to obtain FCD-Se/Res nanoplatforms. FCD-Se/Res can actively recognize P-selectin and penetrate the AS plaque interior. Subsequently, FCD-Se/Res responded to the high shear force and abundant cholesterol in the plaque microenvironment to release Res, reducing AS plaque inflammation by reversing M1 macrophages to M2 phenotype. Meanwhile, TK bonds broke in response to high ROS levels in the plaque, making β-CD free to clear excessive pathogenic cholesterol from plaques. Benefiting from the integrated multifunctionality, FCD-Se/Res can break the vicious cycle between inflammation and disrupted lipid metabolism, jointly stabilize vulnerable plaques, and exert efficient anti-AS effects. The pharmacodynamic results revealed a significantly reduced plaque vulnerability index (VI) from 4.07 to 0.40 after FCD-Se/Res treatment.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"56 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660554","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":"Robust micelles formulation to improve systemic corticosteroid therapy in sepsis in multiple healthcare systems","authors":"Younes Louaguenouni, Qinglin Wang, Thomas Baticle, Catherine Cailleau, Elodie Lamy, Julie Mougin, David Chapron, Stanislas Grassin-Delyle, Juliette Vergnaud, Nicolas Tsapis, Elias Fattal, François Fay","doi":"10.1016/j.jconrel.2025.113635","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113635","url":null,"abstract":"Sepsis is a life-threatening condition resulting from an imbalanced immune response to an infection that causes over 10 million deaths annually, particularly in low and middle-income countries. Current clinical management of sepsis relies on infection control, homeostasis restoration, and systemic corticosteroid therapy. Unfortunately, while beneficial, corticosteroid regimens, including dexamethasone, can lead to adverse effects such as neurological and metabolic complications, limiting their use. In this work, we decided to develop a scalable production method using only approved and cost-effective materials. We also conceived our formulation to be freeze-drying friendly to allow its use within various healthcare systems. Following those concepts, we designed DSPE-PEG(2000)-based micelles to encapsulate dexamethasone, and improve its <em>in vivo</em> efficacy by extending blood circulation time and targeting innate blood immune cells. First, the physicochemical properties, stability, <em>in vitro</em> release kinetics, and efficacy of dexamethasone-loaded micelles were comprehensively measured to demonstrate the platform's robustness. The therapeutic <em>in vivo</em> efficacy of dexamethasone-loaded micelles and their ability to increase animal survival was exhibited in two murine sepsis models, an endotoxemia model, and the cecal ligation and puncture model. Various biodistribution and <em>ex vivo</em> fluorescence imaging assays revealed that using micelles led to an improved blood circulation time and a preferential accumulation within immune cells that could explain the enhanced efficacy of dexamethasone-loaded micelles compared to the soluble form of the drug used clinically. Altogether, our results indicate that this robust micellar delivery system can potentially improve the anti-inflammatory therapy of dexamethasone, offering a safer and more effective alternative to conventional corticosteroid regimens in sepsis.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"8 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660559","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":"Inhalable pH-responsive charge-reversal polymer-small interfering RNA polyplexes for directed gene therapy of anaplastic lymphoma kinase fusion-positive lung cancer","authors":"Jiadong Pang, Xiaoyu Chen, Zhijun Lin, Shuo Yao, Wanyan Wang, Hong Wu, Wei Xing, Jiang Yang","doi":"10.1016/j.jconrel.2025.113644","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113644","url":null,"abstract":"Anaplastic lymphoma kinase (ALK) oncogenic fusions are an infamously evolving target in ALK fusion-positive (ALK⁺) non-small cell lung cancer (NSCLC). RNA interference (RNAi) is a potential alternative to small-molecule ALK inhibitors but suffers from poor cellular delivery and low stability, restricting sustained on-target therapeutic efficacy. To attain non-invasive direct RNAi at target sites in the lungs, inhalable vehicles are demanded to shield unstable siRNA from degradation in alkaline pleural fluid and to shuttle siRNA in the acidic tumor microenvironment. Here, we chemically synthesize a universal polyethylene glycol-poly(β-amino esters)-histidine(PEG-PBAE-His, PPH) system that enables siRNA-directed <em>ALK</em> gene silencing in ALK⁺ NSCLC with controlled release. The rational design of PEGylated polycationic PPH integrates the non-ionic nature, inertness, stealth effect, and low immunogenicity of PEG coronae with dual positively-charged PBAE and His to encapsulate siRNA payloads through enhanced electrostatic complexations. The assembled polyplexes with low polydispersity are overall anionic in alkaline pleural fluid and reversed into cationic charges at acidic pH, facilitating cellular uptake and lysosomal pH-governed release. The PPH-directed delivery significantly improves siRNA stability and ALK sequence-specific knockdown in H3122 cells, with a transfection efficiency comparable to commercial polyethylenimine but with lower cytotoxicity. The ALK-centric RNAi therapy prohibits cancer clonogenicity, migration, and invasion and induces potent growth inhibition in ALK⁺ NSCLC xenografts through inhalation. The inhalable polyplexes represent a transformative delivery platform that combines pH-responsive targeting, enhanced stability, and low toxicity, addressing critical limitations of existing siRNA delivery systems.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"61 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653533","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":"Overcoming P-glycoprotein-mediated multidrug resistance in cancer cells through micelle-forming PHPMA-b-PPO diblock copolymers for doxorubicin delivery","authors":"Martin Kaňa, Alena Braunová, Daniil Starenko, Markéta Frejková, Jan Bouček, Blanka Říhová, Marek Kovář, Tomáš Etrych, Milada Šírová","doi":"10.1016/j.jconrel.2025.113645","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113645","url":null,"abstract":"Multidrug resistance (MDR) represents one of the major concerns in cancer therapy as it may cause reduced efficacy of chemotherapeutic drugs due to the overexpression of ABC transporters, particularly P-glycoprotein (P-gp). This study explores the potential of novel amphiphilic diblock (DB) copolymers composed of poly(<em>N</em>-(2-hydroxypropyl)methacrylamide)-based copolymers (PHPMA) and poly(propylene oxide) (PPO) to overcome MDR mechanisms. The DB copolymers and their doxorubicin (Dox) conjugates significantly increased Dox accumulation in P-gp positive cells, markedly sensitizing them to Dox cytotoxic activity. The underlying mechanisms included depletion of intracellular ATP with subsequent inhibition of P-gp mediated drug efflux, an altered mitochondrial membrane potential, and increased ROS production. Moreover, the DB-Dox conjugates inhibited tumor growth <em>in vivo</em> more effectively compared to the corresponding PHPMA-based drug delivery system. Copolymers with additionally loaded PPO in the micelle core demonstrated superior efficacy in terms of P-gp inhibition, ATP depletion, and chemosensitizing effect <em>in vitro</em>, as well as antitumor activity <em>in vivo</em>. DB copolymers effectively depleted ATP levels both <em>in vitro</em> and <em>in vivo</em> using patient-derived xenograft (PDX) models, underscoring their capacity to enhance the effectiveness of standard chemotherapy and translational potential.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"214 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of administration route and PEGylation on alpha-1 antitrypsin augmentation therapy","authors":"Xiao Liu, Bernard Ucakar, Kevin Vanvarenberg, Etienne Marbaix, Rita Vanbever","doi":"10.1016/j.jconrel.2025.113643","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113643","url":null,"abstract":"Patients suffering from emphysema associated with alpha1 antitrypsin (AAT) deficiency can benefit from augmentation therapy. AAT is administered to the patient once a week by intravenous infusion by a healthcare professional. However, only 2 % of the AAT dose reach the lungs following intravenous infusion. Inhalation of AAT might be a convenient and effective alternative to intravenous infusion. Yet, it has shown limited therapeutic efficacy in a recent clinical trial. Here, we assessed the impact of these routes of AAT administration on AAT pharmacokinetics, lung distribution and therapeutic efficacy in mice. PEGylation of the serpin was employed to improve its therapeutic value. Intravenous injection of AAT or its local administration to the lungs resulted in a similar exposure of the lung parenchyma to AAT with however an AAT dose delivered to the lungs 45-times lower than the injected dose. Conjugation of AAT to a 2-armed 40 kDa polyethylene glycol (PEG) chain prolonged its half-life in plasma and lungs 1.6-times, decreased its penetration in the lung tissue by both routes of administration but did not markedly affect the lung exposure to AAT. The PEG moiety in PEG-AAT was cleared more slowly than the protein moiety and high PEG quantities remained in the lung tissue and alveolar macrophages several days after intratracheal instillation. Pulmonary administration and PEGylation both improved AAT efficacy to prevent lung injury and inflammation in a murine model of chronic obstructive pulmonary disease where lung inflammation was induced by delivering porcine pancreatic elastase and lipopolysaccharide locally to the airways. Anti-AAT and anti-PEG antibodies were generated by AAT and PEG-AAT administration, as expected for a foreign protein. However, anti-PEG antibodies did not significantly contribute to the overall anti-drug antibody titers against the conjugate. AAT and PEG-AAT showed good stability to jet nebulization. This study provides new insights into the impact of administration route and PEGylation on lung exposure, clearance, therapeutic efficacy, and safety of AAT. It highlights that inhalation of AAT might effectively replace its intravenous infusion in augmentation therapy.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"43 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653532","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":"Micelle into gel thermosensitive intra-articular hydrogels for osteoarthritis management","authors":"Helena Rouco, Maria Permuy, Fernando Muñoz, José Antonio Vázquez, José R. Caeiro, Mariana Landin, Patricia Diaz-Rodriguez","doi":"10.1016/j.jconrel.2025.113639","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113639","url":null,"abstract":"Osteoarthritis (OA) is a chronic and degenerative joint disease with a rising incidence worldwide. Current therapeutic approaches primarily focus on symptom relief through systemic administration, which raises safety concerns related to side effects and long-term use. In this context, the local administration of natural compounds with anti-inflammatory and anti-arthritic properties, such as β-Lapachone constitutes an interesting alternative. In this work, we prepared and characterized injectable thermosensitive hybrid hydrogels loaded with β-Lapachone. A comprehensive characterization of the hydrogel systems was performed, including micellar diameter, mechanical properties at different temperatures, the ability to control drug release and microstructure. The anti-inflammatory activity of the free drug, as well as that of the blank or loaded hydrogels was then evaluated <em>ex vivo</em>, using OA cartilage explants. Additionally, <em>in vivo</em> studies were carried out in a rabbit model of OA to assess their clinical potential. The results suggest that the hydrogel systems possess a composite microstructure integrating micelles, together with a temperature-responsive stiffness and the ability to modulate drug release. In addition, β-Lapachone-loaded hydrogels display an interesting immunomodulatory potential <em>ex vivo</em>, as they were able to efficiently reduce the secretion of several proinflammatory mediators, such as IL-6, MMP9, MMP13 and CXCL8. Furthermore, the drug-loaded hydrogels were found to improve <em>in vivo</em> cartilage and bone histomorphometric markers, such as subchondral bone thickness, as well as early signs of cartilage damage, such as the fibrillation index. Therefore, the developed β-Lapachone-loaded thermosensitive hydrogels constitute a promising alternative for OA management.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"55 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635561","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":"Investigation of the impact of lipid nanoparticle compositions on the delivery and T cell response of circRNA vaccine","authors":"Yasir Alshehry, Xiang Liu, Yu Zhang, Guizhi Zhu","doi":"10.1016/j.jconrel.2025.113617","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113617","url":null,"abstract":"Circular RNA (circRNA) is an emerging class of vaccines for various diseases, such as cancer immunotherapy. For cancer therapeutic vaccines, it is critical to deliver circRNA to lymphoid tissues such as lymph nodes (LNs) and dendritic cells (DCs) and then elicit antigen-specific T cell responses. Lipid nanoparticles (LNPs) have shown great success for mRNA vaccines and may also have great potential as nanocarriers for circRNA vaccines. Here, we studied the impact of LNP composition on the efficiency of immune delivery, protein expression, and the T cell responses for circRNA vaccine. First, we used model mRNA and circRNA encoding firefly luciferase (mRNA-fLuc) to study protein expression and used two small circRNA vaccines to study T cell responses. We investigated a combination of six ionizable lipids, three helper lipids, and six different molar ratios of cholesterol and β-sitosterol for their impact on the physicochemical properties of RNA LNPs, <em>in vitro</em> DC transfection, <em>in vivo</em> protein expression in draining LNs, and antigen-specific T cell responses. Among these ionizable lipids, SM-102 was the most effective for DC transfection and enabling circRNA vaccines to elicit T cell responses. DOPE and β-sitosterol incorporation in LNPs resulted in efficient protein expression, albeit β-sitosterol incorporation appeared to be associated with reduced T cell response. Overall, circRNA was efficiently delivered to DCs and macrophages in mouse draining lymph nodes by LNPs of SM-102 (50 %), cholesterol (38.5 %), DOPE (10 %), and DMG-PEG2000 (1.5 %), resulting in the induction of potent antigen-specific CD8⁺ T cell response in mice. These findings may provide insights into designing the compositions of LNPs as the carrier for circRNA therapeutics and vaccines.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"27 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635562","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":"Effects of silica nanoparticles with varied physicochemical properties on the survival and functionality of saturated macrophages","authors":"Sushanto Kumar Saha, Cansu Umran Tunc, Nitish Khurana, Jason William Grunberger, Hamidreza Ghandehari","doi":"10.1016/j.jconrel.2025.113640","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113640","url":null,"abstract":"Silica nanoparticles (SNPs) have shown potential as nanocarriers in diagnostic, imaging, and drug delivery applications. To use SNPs for systemic drug delivery, it is important to have a detailed understanding of how these particles interact with the mononuclear phagocytic system (MPS). Whether or not SNPs may saturate the macrophages, thereby influencing their function and impairing innate immune responses, remains poorly understood. In this work, we defined macrophage saturation using RAW 264.7 macrophages as a model and studied four SNPs with variations in size and porosity. We further explored the downstream effects of SNP uptake by macrophages, including apoptosis/necrosis, cell cycle progression, membrane integrity, and phagocytic activity. The data demonstrate that SNPs do not alter major cellular functions at their respective nontoxic, saturating concentrations.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"17 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635579","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":"In situ peptide assembly for cell membrane rewiring in tumor therapy","authors":"Yu Ma, Qiaochu Jiang, Xiaoyang Liu, Xianbao Sun, Gaolin Liang","doi":"10.1016/j.jconrel.2025.113637","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113637","url":null,"abstract":"Peptide assembly on the cell membrane is capable of endowing cells with novel biological properties that are distinct from their original states, thereby playing a pivotal role in the regulation of diverse cellular biological events. In practical biomedical scenarios, in order to make peptide assembly more precisely meet the requirements of cells at different physiological stages and conditions to achieve desired effects of cell function regulation, it becomes particularly crucial to conduct precise <em>in situ</em> spatiotemporal control of peptide assembly on the cell membrane, thus attracting great attentions. Particularly for tumor treatment, this artificially manipulated cell surface engineering can achieve excellent anti-tumor effects by altering the cell membrane structure, influencing receptor clustering or interfering with relevant signal pathways. Of note, membrane-anchoring peptides play a key role in these processes. In this review, we focus on three main types of membrane-anchoring peptides, elaborating in detail on how their assembly regulation mechanisms influence the cell membrane remodeling effect, and further exert therapeutic effects on tumors. On this basis, we further introduce a variety of tumor treatment strategies combined with <em>in situ</em> peptide assembly on the cell membrane, and discuss the current opportunities and challenges in this field, aiming to present the overall research panorama and trend of <em>in situ</em> peptide self-assembly on the cell membrane for efficient tumor treatment.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"89 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639967","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}