Journal of Controlled Release最新文献

{"title":"Scalable cultured gut microbiota-derived nanovesicles for oral augmentation of checkpoint blockade therapy.","authors":"Lin Chen, Nilupaier Tayier, Hao Wu, Guangnian Liu, Shuai Wang, Yu Zhu, Jiayi Sun, Yining Niu, Chenchao Feng, Liwei You, Guang Hu, Xiaoqing Cao, Huiying Liu, Motao Zhu","doi":"10.1016/j.jconrel.2026.115456","DOIUrl":"10.1016/j.jconrel.2026.115456","url":null,"abstract":"<p><p>Microbiota-targeted strategies, such as fecal microbiota transplantation (FMT), hold promise for enhancing immunotherapy but face clinical challenges including safety risks, batch-to-batch variability, and dependence on substantial quantities of donor fecal material. To overcome these limitations, we established a standardized in vitro expansion platform for responder patient-derived gut microbiota. Through optimization of culture conditions, we achieved stable viability and retention of key immunotherapy-enhancing strains over serial passages, enabling a scalable 6.4 × 10⁷-fold expansion. Leveraging this platform, we engineered hybrid nanovesicles derived from bacterial protoplasts, followed by silica surface coating (HNVs@Silica) for oral delivery. The silica shell significantly improved nanovesicle stability under gastrointestinal conditions and conferred superior antitumor efficacy compared with uncoated counterparts. Notably, HNVs@Silica produced from the 2nd, 4th, and 6th passages retained comparable potency in augmenting anti-PD-1 (αPD-1) therapy. Mechanistically, HNVs@Silica remodeled intestinal immunity, particularly within Peyer's patches, by activating and expanding effector CD8⁺ T cells. This local response enhanced the priming and systemic dissemination of tumor-specific T cells, thereby improving the efficacy of αPD-1. Collectively, our findings establish a safe, scalable, and orally bioavailable alternative to FMT for enhancing cancer immunotherapy.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115456"},"PeriodicalIF":12.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182176","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 nanocomposite hydrogel enabling spatial redox compartmentalization for endogenous Cu(I) hijacking and durable cuproptosis-mediated tumor vaccination.","authors":"Sheng Zhao, Yongyi Qu, Wei Chen, Ruotong Li, Jing Zhu, Yunyun Wu, Lunli Xiang, Lin Li, Hongrui Zhu, Jixi Zhang","doi":"10.1016/j.jconrel.2026.115457","DOIUrl":"10.1016/j.jconrel.2026.115457","url":null,"abstract":"<p><p>Cuproptosis-based in situ tumor vaccination provides a unique opportunity to transform tumor destruction into systemic antitumor immunity. However, the oxidative stress required for efficient tumor killing simultaneously disrupts immune competence through copper toxicity and immunosuppressive remodeling. Herein, we develop a spatial redox compartmentalized nanocomposite hydrogel platform to resolve this paradox by selectively amplifying intracellular cuproptosis while preserving the extracellular immune niche. Following peritumoral co-injection of gallic acid-grafted chitosan (CS-GA), dopamine-grafted oxidized hyaluronic acid (OHA-DA), and neocuproine-caffeic acid (NCP-CA) nanoparticles, the hydrogel establishes distinct redox microdomains for tumor eradication and immune protection. Specifically, NCP selectively exploits endogenous exchangeable Cu(I) pools and redirects copper toward mitochondria, where copper valence transformation and ferredoxin 1-mediated activation induce dihydrolipoamide S-acetyltransferase oligomerization, mitochondrial proteotoxic stress, and cuproptotic immunogenic cell death. Meanwhile, CA treatment was associated with increased AMPK phosphorylation and a 63.5% reduction in PD-L1 expression. Simultaneously, catechol-mediated redox cycling by CS-GA&OHA-DA continuously scavenges extracellular reactive oxygen species, alleviating oxidative immunosuppression and restoring T-cell viability to 94.4%. After 14 days of treatment, a substantial tumor regression was observed with a tumor volume reduction exceeding 64.2%. In a contralateral tumor rechallenge model, enhanced infiltration of CD8⁺ T-cells (40.8%) and CD8⁺ T_EM-cells (26.4%) contributed to 75.6% inhibition of tumor recurrence and 93.3% suppression of metastasis. By exploiting endogenous copper resources rather than exogenous copper supplementation and spatially decoupling tumoricidal oxidation from immune-protective antioxidation, this hydrogel platform establishes a new approach for cuproptosis-based in situ vaccination, inducing durable antitumor immune memory and effectively preventing postoperative tumor recurrence and metastasis.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115457"},"PeriodicalIF":12.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182167","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":"Ischemic myocardium-targeted NAD⁺ nanotherapy mitigates myocardial ischemia/reperfusion injury.","authors":"Xiahong Xie, Xiangna Zhang, Zheng Zhou, Congli Han, Kanghua Zeng, Luyao Wang, Jingfeng Chen, Ye Zhang, Yi Zhang, Mingzhou Ye","doi":"10.1016/j.jconrel.2026.115454","DOIUrl":"10.1016/j.jconrel.2026.115454","url":null,"abstract":"<p><p>Myocardial ischemia-reperfusion injury remains a major cause of cardiomyocyte loss and adverse remodeling following acute myocardial infarction, yet effective therapeutic options remain limited. Although nicotinamide adenine dinucleotide (NAD⁺) plays a central role in mitochondrial function and redox homeostasis, its therapeutic application is limited by poor membrane permeability and inefficient restoration of intracellular NAD⁺ pools. Here, we developed a cardiac-targeted lipid-polymer hybrid nanoparticle (LN-DPC) that enables efficient intracellular delivery of NAD⁺ to ischemic myocardium. The nanoparticale integrates boronate-guanidine-mediated NAD⁺ encapsulation with an ischemic myocardium-homing peptide (CSTSMLKAC), achieving stable loading, controlled release, and preferential accumulation in injured cardiac tissue. In vitro, LN-DPC enhanced cellular uptake and restored intracellular NAD⁺ levels, leading to improved mitochondrial function, reduced reactive oxygen species generation, and alleviation of calcium overload under OGD/R conditions. In vivo, the nanoparticles preferentially accumulated in the injured myocardium, attenuated early inflammation, significantly reduced infarct size, improved cardiac function, and markedly limited chronic fibrosis. Mechanistically, NAD⁺ delivery restored SIRT3 expression, improved mitochondrial homeostasis, and suppressed HMGB1-RAGE signaling to mitigate secondary myocardial injury; pharmacological SIRT3 inhibition attenuated the protective effects of LN-DPC both in vitro and in vivo, supporting a functional contribution of SIRT3 to LN-DPC-mediated cardioprotection. Collectively, this work establishes targeted NAD⁺ delivery as an effective strategy to restore metabolic homeostasis and protect against ischemia-reperfusion injury, and provides a nanomedicine platform for metabolic intervention in cardiovascular diseases.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115454"},"PeriodicalIF":12.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167338","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":"Emerging bacterial membrane vesicles from microbial messengers to therapeutic nanocarriers.","authors":"Giulia Elayna Stewart, Yitong Guo, Shijie Cao","doi":"10.1016/j.jconrel.2026.115250","DOIUrl":"10.1016/j.jconrel.2026.115250","url":null,"abstract":"<p><p>Bacterial membrane vesicles (BMVs) are nanoscale vesicles that are naturally released by bacteria into the extracellular environment. By retaining the bacterium's membrane and luminal cargo, BMVs represent natural nanocarriers and long-distance messengers capable of influencing human health and disease progression. Depending on the bacterial species of origin, BMVs present important transport roles by carrying diverse native molecular cargo, protecting luminal cargo from degradation, promoting intracellular delivery and cytosolic release, crossing biological barriers, and mediating interactions with host cells. Recently, engineering strategies have emerged to harness these natural nanocarriers for the improved delivery of a wide range of therapeutic cargos, including proteins, antigens, nucleic acids, oncolytic viruses, polymers, and nanoparticles. These engineering strategies include genetic engineering, encapsulation, surface modification, and detoxification methods. Together, these strategies provide features including superior loading efficiency, targeted delivery, controlled release, longer circulation time, and multi-composite delivery approaches. This review discusses BMVs as versatile, multi-functional, and bio-active delivery vehicles along with current preparation methods, delivery routes, engineering strategies, highlighting unique features and challenges for translation.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115250"},"PeriodicalIF":12.4,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760530","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":"Nanomedicine for targeting crosstalk between nerves and cancer.","authors":"Xinbo Yu, Guilin Xiang, Han Wang, Xiaoqiang Li, Hanwei Huang, Shuhui Song, Qi Xi, Jia Zhao, Funan Liu","doi":"10.1016/j.jconrel.2026.115269","DOIUrl":"10.1016/j.jconrel.2026.115269","url":null,"abstract":"<p><p>The emerging field of cancer neuroscience has revealed the nervous system as a dynamic regulator of tumors and the tumor microenvironment. Neural activity influences tumor progression through electrical signaling, neurotransmitter and neuropeptide release, and interactions with immune cells. The direction and magnitude of these effects vary according to neuronal subtype, receptor expression, target cell, and tumor context. Neural inputs may either promote or suppress tumor growth and anti-tumor immunity, although protumorigenic and immunosuppressive pathways remain the most extensively characterized. Conversely, tumors remodel neural circuits to accelerate their growth and trigger severe neurological complications, such as cancer pain. These bidirectional interactions make the nerve-cancer interface a compelling therapeutic target. Nanomedicine offers significant promise in this context, leveraging its adaptability in drug delivery. Specifically, surface functionalization allows targeted delivery of neuromodulators, precisely modulating the tumor-associated neural niche. Moreover, nanomedicine can be rationally designed to ensure biocompatibility, physiological stability, controlled release, and penetration across biological barriers. It can also co-deliver therapeutic and imaging agents for combined or theranostic applications. This review systematically summarizes the mechanisms underlying nerve-cancer interactions and evaluates their therapeutic potential through nanomedicine. We highlight emerging nanomedicine-based strategies for treating tumors and cancer pain, including single-modality neural modulation, multimodal combination therapies, and imaging-guided approaches. Finally, we address current challenges and future directions, aiming to inspire innovative approaches for comprehensive cancer therapy.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115269"},"PeriodicalIF":12.4,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766356","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":"Combining imaging strategies with physiologically-based pharmacokinetic modeling to improve precision dosing & drug delivery in brain tumors.","authors":"Tamara Jordens, Anne-Jaël Elskamp, Imke H Bartelink","doi":"10.1016/j.jconrel.2026.115451","DOIUrl":"10.1016/j.jconrel.2026.115451","url":null,"abstract":"<p><p>Small molecule targeted therapies frequently fail to control brain metastases and primary brain tumors even when systemic exposure reaches toxicity-limiting levels. Systemic exposure-response relationships are often absent, which is well documented for tyrosine kinase inhibitors. Target-site information is therefore needed, since the concentration reached in the tumor is determined not by plasma exposure, but by passive and active transport across the blood-brain barrier and by intratumoral heterogeneity. Physiologically-based pharmacokinetic (PBPK) modeling provides the mechanistic framework to describe this. Models built solely on in vitro-to-in vivo extrapolation of permeability and transport have repeatedly required correction factors derived from rodent data, and their evaluation in humans still depends on invasive sampling or microdialysis. Microdialysis performs poorly for lipophilic, highly protein-bound drugs. We argue that quantitative imaging can supply the missing in vivo input. In a hybrid strategy, in vitro-derived transport parameters serve as the starting point, while blood-brain barrier influx and efflux are recalibrated on positron emission tomography (PET) microdose measurements in patients. This could lead to improved prediction of brain concentrations at therapeutic doses and allows simulated target-site exposure to be weighed against in vitro potency for compound and dose selection. Beyond whole-brain averages, magnetic resonance imaging (MRI) can provide permeability and perfusion parameters longitudinally and in larger cohorts, whereas mass spectrometry imaging (MSI) techniques can map intratumoral heterogeneity in drug distribution in the tumor microenvironment and identify potential sanctuary sites. We map each modality onto the specific PBPK parameters it can inform, and argue that imaging-informed, spatially resolved PBPK is a realistic route toward model-informed precision dosing in neuro-oncology.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115451"},"PeriodicalIF":12.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147899","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 reactive oxygen species for advanced drug delivery and therapeutics","authors":"Jae Hyung Park,Andrew Wang,Hélder A. Santos","doi":"10.1016/j.jconrel.2026.115437","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115437","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"110 1","pages":"115437"},"PeriodicalIF":10.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088418","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":"The role of glycocalyx-protein corona interactions in the cell type-specific uptake of mRNA nanocarriers","authors":"Ward Jacobs,Klarinda de Zwaan,Luco Rutten,Thierry van Wessel,Thomas J. Boltje,Laia Querol Cano,Christian Büll,Nico Sommerdijk,Lorenzo Albertazzi,Roland Brock","doi":"10.1016/j.jconrel.2026.115440","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115440","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"24 1","pages":"115440"},"PeriodicalIF":10.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088425","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 indocyanine green-potentiated gastrin releasing peptide receptor-targeting multifunctional peptide-drug conjugate for prostate cancer therapy","authors":"Hao Tian, Zihan Huang, Xiangding Liu, Quan Zuo, Jiang Wu, Xueyao Chen, Xin Gao, Dengfu Wu, Xingkai Wang, Hongyi Huang, Shuo Jiang, Yuxin Song, Siqi Zhang, Feng Wang, Peng Liu, Rui Wang, Kuan Hu","doi":"10.1016/j.jconrel.2026.115260","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115260","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"6 1","pages":"115260"},"PeriodicalIF":10.8,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754907","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":"Exosomes as next-generation drug carriers: Transforming cancer therapy.","authors":"Yaseera Arif, Disha Nagesh Moholkar, Raghuram Kandimalla, Farrukh Aqil, Ramesh C Gupta","doi":"10.1016/j.jconrel.2026.115265","DOIUrl":"https://doi.org/10.1016/j.jconrel.2026.115265","url":null,"abstract":"<p><p>Cancer remains a major global health challenge, with its growing incidence highlighting the critical need for effective and accessible treatments. Current therapeutic approaches, including surgery, chemotherapy, radiation therapy, hormone therapy, and immuno-therapy, are often limited by toxicity, poor targeting, and suboptimal efficacy. These challenges have driven the development of nanotechnology-based strategies aimed at improving tumor selectivity and therapeutic outcomes. Among the most promising are extracellular vesicles, particularly exosomes (30-150 nm), which have garnered significant attention as natural nanocarriers due to their inherent role in intercellular communication and their capacity to encapsulate proteins, nucleic acids, and lipids. Exosomes can be obtained from a wide range of sources, including biological fluids, cell cultures, and unconventional origins such as plants and microorganisms. Of particular interest are milk- and colostrum-derived exosomes, particularly those of bovine origin, have emerged as a promising delivery platform owing to their scalability, biocompatibility, cost-effectiveness and suitability for oral administration. These vesicles possess immunomodulatory properties, demonstrate stability under gastrointestinal conditions, and are readily internalized by intestinal epithelial cells. Furthermore, surface engineering with targeting ligands such as folic acid can enhance tumor specific delivery by exploiting receptor overexpression while minimizing systemic toxicity. This review critically examines exosome sources, isolation and characterization methodologies, cargo-loading strategies, biodistribution, pharmacokinetics, and engineering approaches together with their applications in delivering small-molecule drugs and nucleic acid-based therapeutics to overcome multidrug resistance in cancer. In addition, current challenges related to exosome heterogeneity, manufacturing, quality control, clinical translation, and regulatory considerations are discussed, together with future perspectives for the development of exosome-based therapeutics.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":"115265"},"PeriodicalIF":12.4,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759832","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}