Journal of Controlled Release最新文献

{"title":"Functional lipid nanoparticles for safe delivery of macromolecular antibiotics to gram-negative bacteria","authors":"Melgious J.Y. Ang, Nithiyaa Balakrishnan, Ki Hyun Bae, Qiangqiang Wang, Zhengjie Wu, Yanming Wang, Pinzheng Zhang, Brandon Y.L. Seow, Xiaoli Liu, Yi Yan Yang","doi":"10.1016/j.jconrel.2025.113907","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113907","url":null,"abstract":"Lipid nanoparticle<strong>s</strong> (LNP<strong>s</strong>) hold great potential for delivery of macromolecular antimicrobials. Herein, we designed a series of anionic LNPs capable of delivering cationic polymyxin B (PMB) for effective and safe treatment of Gram-negative bacterial infection. The use of anionic lipid induced self-assembly of PMB, encapsulating cationic PMB molecules in<strong>to</strong> LNPs <em>via</em> electrostatic interactions (PMB-LNPs). Anionic lipid architecture and lipid:PMB mixing ratios had a substantial influence on particle size, surface charge, and drug release properties of PMB-LNPs. Following <em>in vitro</em> screening assays, C14-Glu₅/PMB (1:4) LNP was identified as the lead formulation due to its potent bactericidal activity against a panel of tested Gram-negative bacteria strains. Confocal and SEM imaging studies validated the importance of fractionated PMB release in mediating the enhanced binding of C14-Glu₅/PMB (1:4) LNPs on the bacterial outer membrane. Additionally, PMB-LNPs conferred prolonged blood circulation, preferential liver accumulation, and superior tolerability over free PMB. In a murine neutropenic <em>A. baumannii</em> infection model, administration of C14-Glu₅/PMB LNPs eliminated bacteria in the liver and suppressed bacterial regrowth in the kidney more effectively than free PMB, resulting in an improved body weight status and histological appearance. This study may provide insights into the <em>de novo</em> design of LNP-based nanomedicines for antimicrobial therapies.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"98 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176956","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":"Topical delivery of cultivated limbal stem cells via porous photocurable hydrogel: A noninvasive, convenient, and efficient stem cells delivery strategy for limbal stem cell deficiency","authors":"Shujia Guo, Yi Han, Jiani Li, Yuhan Huang, Dong Yu, Yuwen Liu, Yuqian Wang, Chaoyu Fan, Yimin Huang, Wenyin Guan, Danyi Qin, Lan Zheng, Caihong Huang, Cheng Li, Jiaoyue Hu, Zuguo Liu","doi":"10.1016/j.jconrel.2025.113900","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113900","url":null,"abstract":"Topical administration of stem cells is one of the simplest approaches to stem cell-based therapy for limbal stem cell deficiency (LSCD). Without timely supplementation of deficient stem cells, LSCD may worsen, carrying a high risk of blindness in severe cases. However, challenges such as stem cell loss, poor cell attachment, short retention time, and phenotypic transformation of stem cells limit the efficiency of direct stem cell delivery. To address these problems, this study conducted <em>in vitro</em> and <em>in vivo</em> screenings of photocurable hydrogels and identified a porous Gelatin Methacryloyl (PG) hydrogel with larger pore sizes prepared by phase separation technology that satisfies four critical conditions: (i) encapsulating stem cells before delivery, (ii) maintaining the viability and self-renewal of stem cells <em>via</em> activation of the non-canonical Wnt signaling pathway, (iii) adhering uniformly to the ocular surface, and (iv) supporting stem cell proliferation, migration, and adhesion to the target interfaces. In a rabbit model of LSCD, the PG hydrogel loaded with cultivated limbal stem cells was applied to the ocular surface in combination with corneal bandage lenses, enabling a sutureless, non-invasive, convenient, and efficient stem cell delivery system. This innovative delivery strategy not only greatly simplified the existing process of limbal stem cell transplantation and significantly reduced surgery time, but also successfully overcame the challenges associated with direct stem cell eye drops. Most importantly, it promoted corneal injury repair, achieving avascular and scar-free corneal regeneration.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"58 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176955","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":"COG133 peptide-conjugated lipid nanoparticles sensitize medulloblastoma to radiation therapy in mice","authors":"Aditya Gupta, Sohan Mahto, Rebecca E. Oberley Deegan, Donald W. Coulter, Ram I. Mahato","doi":"10.1016/j.jconrel.2025.113902","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113902","url":null,"abstract":"Medulloblastoma (MB) is a malignant brain tumor that often arises in the cerebellum and has a propensity for spreading to the spinal cord or other parts of the central nervous system (CNS). Craniospinal irradiation (CSI) has long been a cornerstone in the treatment of MB, especially for patients with high-risk or metastatic disease. However, CSI often leads to long-term neurocognitive deficits, including learning disabilities, and growth abnormalities, especially in children. In this study, we aimed to decrease the dose of irradiation and the proliferation of MB by using Volasertib (VSB), a Polo-like kinase 1 (PLK1) specific inhibitor. VSB was highly potent in-vitro with an IC₅₀ of 27.43 nM and 13 nM in HDMB03 and DAOY cells, respectively. However, in the orthotopic MB mouse model, VSB as a free drug did not improve overall survival or decrease tumor burden. Hence, we encapsulated VSB in COG133-conjugated lipid nanoparticles (COG133-LNPs) to circumvent the blood-brain barrier (BBB). We observed that COG-133-LNPs loaded with VSB increased the biodistribution of VSB by three folds than the non-targeted LNPs in the brain. Furthermore, COG133-LNPs along with irradiation decreased tumor burden significantly as compared to VSB or radiation alone. To our observation, COG133-LNPs display high potency in killing MB cells and sensitizing them toward radiation therapy.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"5 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176959","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":"Anti-CD33 antibody enhances liposomal co-delivery of cytarabine and daunorubicin for targeted combination chemotherapy","authors":"Jinyang Li, Jiasheng Lu, Xin Huang, Yuan Ding, Jianfen Zhou, Ruohan Chen, Zhixuan Jiang, Xingyan Fan, Yilin Yang, Chongbing Liao, Weiyue Lu, Wuyuan Lu","doi":"10.1016/j.jconrel.2025.113899","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113899","url":null,"abstract":"The combination chemotherapy of cytarabine and daunorubicin (7 + 3 standard regimen) has stood as the mainstay treatment against acute myeloid leukemia for decades. Recent advances in nanomedicine have led to the development of Vyxeos®, a liposomal formulation of cytarabine/daunorubicin fixed in a synergistic 5:1 M ratio. The synchronized pharmacokinetics and biodistribution of the partner chemotherapeutic agents in Vyxeos® contribute to a significantly higher complete remission rate compared to the traditional 7 + 3 regimen. However, Vyxeos® did not markedly enhance the safety profile, exhibiting similar types and severities of adverse events. To mitigate adverse reactions as well as intensify 7 + 3 combination chemotherapy, we leveraged a functionalization strategy, engineering a humanized anti-CD33 antibody-modified liposome carrier to actively co-deliver cytarabine and daunorubicin. Differing from DSPC/DSPG-based liposomal formulation of Vyxeos®, we developed a PEGylated HSPC liposome with high cholesterol content to proportionally co-load the two agents. Surface reaction via maleimide-thiol chemistry realized anti-CD33 antibody functionalization, demonstrating superior in-vivo therapeutic efficacy compared to plain liposomal drug formulations (<em>p</em> &lt; 0.001) and moderately reduced non-specific adverse effects in the heart and kidneys.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"35 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176960","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":"Injectable hydrogel-based drug formulation for enhancing tertiary lymphoid structure formation and cancer immunotherapy efficacy","authors":"Chaiyaporn Kuwentrai, Weilong Tang, Xuansheng Lin, Teng Chi, Dongping Liu, Erwei Song, Matthew J. Webber, Jian-Dong Huang, Zhou Ye","doi":"10.1016/j.jconrel.2025.113897","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113897","url":null,"abstract":"Tertiary lymphoid structures (TLSs) in the tumor microenvironment are associated with improved cancer prognosis and enhanced immune checkpoint blockade (ICB) responses. In this study, an injectable hydrogel-based drug formulation is developed to stimulate TLSs formation in a B16-OVA melanoma mouse model. A hydrogel, termed HA-CPP⸦CB (Cabrita et al., 2020 [<span><span>8</span></span>]), is formed by supramolecular interactions between 4-(4-chlorophenyl)pyridine modified hyaluronic acid (HA-CPP) and cucurbit [<span><span>8</span></span>]uril (CB (Cabrita et al., 2020 [<span><span>8</span></span>])). The results reveal that a single injection of HA-CPP⸦CB (Cabrita et al., 2020 [<span><span>8</span></span>]) hydrogel containing the CXCL13 chemokine and LIGHT cytokine effectively increases TLSs density, facilitates mature TLSs formation, suppresses tumor growth, and extends survival. Importantly, the hydrogel treatment also up-regulates the number of antigen-specific T-cells in the secondary lymphoid organs. Furthermore, combination of the hydrogel-based drug formulation and the anti-PD1 ICB therapy results in increased tumor suppression, improved survival rates, and strengthened TLSs formation, ultimately contributing to B16-OVA melanoma eradication. In conclusion, this study demonstrates the potential application of hydrogel-based drug carriers as synthetic immune niche scaffolds for promoting mature-like TLSs formation within the B16-OVA melanoma tumor microenvironment, offering a promising strategy for advancing tumor immunotherapy.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"57 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176957","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-enhanced ROS-responsive camptothecin prodrug nanoparticles elicit safe and efficient intravesical instillation therapy of bladder cancer","authors":"Kunpeng Liu, Binbin Jiao, Guan Zhang, Zhihua Gan, Shicong Lai, Zhenshan Ding, Qingsong Yu","doi":"10.1016/j.jconrel.2025.113905","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113905","url":null,"abstract":"Bladder cancer remains a significant clinical challenge, necessitating the development of innovative therapeutic strategies. Recent advancements have highlighted the potential of reactive oxygen species (ROS)-responsive drug delivery systems in cancer therapy. In this study, we introduce a novel treatment approach utilizing a ROS-responsive camptothecin (CPT) prodrug encapsulated within chitosan nanocarrier, named CACPT. Cinnamaldehyde (CA), acting as a ROS generator, forms thioketal bonds with CPT to create a prodrug that responds selectively to the elevated ROS levels within the tumor microenvironment. Upon exposure to high ROS conditions, these thioketal bonds are cleaved, resulting in the simultaneous release of CPT and CA. The liberated CA further enhances ROS production, establishing a positive feedback loop that amplifies the therapeutic effect. The use of amphiphilic chitosan nanocarriers enhances the retention and penetration of the prodrug within bladder tissue, optimizing its therapeutic potential. Our experimental findings demonstrate that this self-enhanced ROS-responsive release promotes increased cellular uptake and significantly enhances the anticancer efficacy of CACPT. These results position CACPT as a promising candidate for orthotopic infusion therapy in bladder cancer, potentially overcoming current limitations in treatment options. The innovative combination of ROS-responsive mechanisms and chitosan nanocarriers represents a paradigm shift in bladder cancer therapeutics, offering a multifaceted approach with substantial promise for clinical translation.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"26 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176958","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":"Double-layered core-shell microneedle patch integrated with microparticles for long-acting treatment of osteoporosis","authors":"Bo Xu, Suohui Zhang, Han Liu, Guozhong Yang, Zequan Zhou, Yunhua Gao","doi":"10.1016/j.jconrel.2025.113898","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113898","url":null,"abstract":"Osteoporosis is one of the most common diseases affecting the elderly, particularly postmenopausal women. It significantly increases the risk of fractures, reduces quality of life, and adds to the medical burden. Traditional formulations, such as alfacalcidol (ALF) capsules and tablets, have limitations, including difficulties in swallowing and patient resistance to long-term medication use, highlighting the urgent need for a sustained-release ALF formulation. To address this, we developed a double-layered core-shell microneedle patch integrated with ALF-loaded microparticles for the long-acting treatment of osteoporosis. This system aims to reduce administration frequency and improve patient compliance. After application for just 5 min, the patch can be removed, leaving the microneedle tips embedded in the skin. The core-shell structure of the tip consists of a core made of ALF-loaded polylactic-<em>co</em>-glycolic acid (PLGA) microparticles and a shell composed of ethylcellulose (EC). This structure acts as a drug reservoir within the skin, enabling for sustained release of ALF over 14 days. Compared to commercially available ALF tablets which require daily administration, the long-acting ALF double-layered core-shell microneedle patch (ALF-DCSMN) delivers a lower systemic drug dose while demonstrating comparable or better efficacy in increasing bone mass and improving trabecular microstructure. Notably, ALF-DCSMN only requires semimonthly administration. Overall, these promising results suggest that the ALF-DCSMN is a safe, effective, and user-friendly transdermal formulation for the long-acting treatment of osteoporosis.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"5 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164846","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":"Intestinal retentive delivery system for improved disease therapy","authors":"Xin Wu, Wantao Wu, Nam Jutaek, Lei Rong, Kai Han","doi":"10.1016/j.jconrel.2025.113903","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113903","url":null,"abstract":"Oral drug delivery systems (DDSs) show great advantages in patient compliance due to their convenience and non-invasiveness. Typically, oral DDSs are designed to deliver drugs to the specific gastrointestinal region, and normalize the dysregulated intestinal niche <em>in situ</em>, or facilitate their transport across the biological barriers including mucus and epithelial layers. Prolonging the residence time of oral DDSs in the gastrointestinal tract is indispensable in realizing these goals. However, the hostile gastric environment is not suitable for the retention of susceptible drugs. Intestinal retentive DDSs are promising alternatives for the oral delivery of these drugs. Moreover, intestinal retentive DDSs can provide opportunities for the regulation of mucosal immunity and gut microbiota. In this review, we briefly describe the general information of intestinal transit time and its influencing factors. We next summarize the recent advances of engineering strategies in prolonging the intestinal retention of oral DDSs at nano-, micro-, and macro-scales. While the underlying mechanisms of intestinal retention remain incompletely understood, we discuss the potential theories and evidence. In addition, we discuss how this prolonged retention of oral DDSs modulates the intestinal environment <em>in situ</em> and the systemic immunity.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"95 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164847","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":"A novel cationic liposome-formulated toll like receptor (TLR)7/8 agonist enhances the efficacy of a vaccine against fentanyl toxicity","authors":"Fatima A. Hamid, Nguyet-Minh Nguyen Le, Daihyun Song, Hardik Amin, Linda Hicks, Sophia Bird, Karthik Siram, Brooke Hoppe, Borries Demeler, Jay T. Evans, David Burkhart, Marco Pravetoni","doi":"10.1016/j.jconrel.2025.113901","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113901","url":null,"abstract":"The U.S. opioid epidemic is an extraordinary public health crisis that started in 1990 and significantly accelerated in the last decade. Since 2020, over 100,000 fatal drug overdoses have been reported annually, and 75 % of those involved fentanyl and its analogs (F/FA). Accelerating the translation of innovative, effective, and safe treatments is needed to augment existing measures to counteract such a crisis. Active immunization against F/FA and other opioids represents a promising therapeutic and prophylactic strategy for opioid use disorder (OUD) and opioid-induced overdose toxicity. Previously we demonstrated that the anti-fentanyl vaccine comprising a fentanyl-based hapten (F) conjugated to the diphtheria cross-reactive material (CRM), admixed with the novel lipidated toll-like receptor 7/8 (TLR7/8) agonist INI-4001 adsorbed on Alhydrogel® (alum) induced high-affinity fentanyl-specific polyclonal antibodies that protected against fentanyl-induced pharmacological effects in mice, rats, and mini-pigs. Here, INI-4001 was formulated into liposomes with different surface charges, and their impact on F-CRM adsorption, INI-4001 adjuvanticity, and vaccine efficacy were explored. Additionally, as the role of innate immunity in mediating the efficacy of addiction vaccines is largely unknown, we tested these formulations on the activation of innate immunity <em>in vitro</em>. Cationic INI-4001 liposomes surpassed other liposomal and aluminum-based formulations of INI-4001 by enhancing the efficacy of fentanyl vaccines and protecting rats against bradycardia and respiratory depression by blocking the distribution of fentanyl to the brain. Fentanyl vaccines adjuvanted with either cationic INI-4001 liposomes or the aqueous INI-4001 adsorbed to alum induced significant surface expression of co-stimulatory molecules and maturation markers in a murine dendritic cell line (JAWS II), while the former was superior in enhancing the macrophages surface expression of CD40, CD86 and inducible nitric oxide synthase (iNOS), indicative of maturation and activation. These results warrant further investigation of liposome-based formulations of TLR7/8 agonists for improving the efficacy of vaccines targeting F/FA and other opioids of public health interest.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"22 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145533","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 stimuli responsive nanoparticle systems for the controlled, intracellular delivery of immunotherapeutic and chemotherapeutic agents","authors":"Dennis Huang ,&nbsp;Ishaan Duggal ,&nbsp;Brandon Chau Matthews ,&nbsp;Elaine Lee ,&nbsp;Eric Tong ,&nbsp;Nicholas A. Peppas","doi":"10.1016/j.jconrel.2025.113878","DOIUrl":"10.1016/j.jconrel.2025.113878","url":null,"abstract":"<div><div>Advanced cancer therapeutic strategies are rapidly evolving due to a better fundamental understanding of cancer cell biology and the complex tumor microenvironment. There is a need for better rational design of bioresponsive nanotherapeutics to take cues from the tumor microenvironment and better facilitate the intracellular delivery of multiple cancer therapeutic agents. Biodegradable, cationic nanogels were synthesized via a UV-initiated free radical emulsion polymerization to impart environmentally responsive behavior for the intracellular delivery of immunotherapeutic and chemotherapeutic agents. The 2-(diethylamino) ethyl methacrylate based copolymeric nanogels exhibited pH responsive behavior that was optimized for the pH gradient of the tumor microenvironment and endosomal compartments of cancer cells. Then, the cationic nanogels were assessed for their ability to load and release various chemotherapeutic and immunotherapeutic agents. Finally, the copolymeric nanoparticle system was evaluated in vitro for biocompatibility, cellular internalization, and therapeutic efficacy. This combination treatment strategy will provide an excellent foundation for the rational design and development of the next generation of drug delivery systems.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"384 ","pages":"Article 113878"},"PeriodicalIF":10.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153936","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}