Journal of Controlled Release最新文献

{"title":"Mesalamine premix-based delayed release formulation and its efficacy assessment using a 3D in-vitro gut model for inflammatory bowel disease","authors":"Sunil Kumar Sah ,&nbsp;Mamta Kumari ,&nbsp;Lohare Rahul Sanjay ,&nbsp;Makka Krupali Ashokbhai ,&nbsp;Ujjwal Gupta ,&nbsp;Subhadeep Roy ,&nbsp;Santanu Kaity","doi":"10.1016/j.jconrel.2026.114672","DOIUrl":"10.1016/j.jconrel.2026.114672","url":null,"abstract":"<div><div>Mesalamine is a widely used drug for inflammatory bowel disease (IBD) but suffers from limited solubility, permeability, and multiple formulation challenges. In this study, we tried to tune mesalamine's Biopharmaceutical Classification System (BCS) properties using premix technology to enhance its solubility and intestinal permeability, and to develop a delayed-release formulation. Mesalamine premix was prepared by the spray drying technique. Particle size analysis (PSA), solubility study, Fourier-transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and <em>in-vitro</em> dissolution study were performed to characterize the premix. The premix showed reduced particle size, higher solubility, and lower crystallinity compared to pure mesalamine. Thermal analyses confirmed improved stability, while SEM revealed spherical morphology. Epithelial and endothelial permeability studies using Caco-2, HUVEC, and heterogeneous co-culture (Caco-2/HT-29/M1 macrophage) models assessed increased permeation potential. It shows its efficacy in a pro-inflammatory (M1) macrophage-induced intestinal inflammatory condition in a heterogeneous co-culture. An <em>in-vitro</em> dissolution study of the novel mesalamine delayed-release tablet showed no drug release at 0.1 N HCl (pH 1.2), and complete drug release at pH 6.8, while marketed tablets released the drug more slowly due to the enteric coating. Thus, the formulation approach showed potential as a delayed-release mesalamine oral formulation, which can be used for drug targeting to the colon without the need for a functional coating on the tablet.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114672"},"PeriodicalIF":11.5,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072207","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":"Nitrate-responsive genetically engineered probiotics locally release TNF-α nanobodies against inflammatory bowel disease","authors":"Bochuan Yuan ,&nbsp;Zhangyu Li ,&nbsp;Yuanyuan Song ,&nbsp;Yaqian Zhang ,&nbsp;Feng Zhang ,&nbsp;Ke Wang ,&nbsp;Lina Du ,&nbsp;Yiguang Jin","doi":"10.1016/j.jconrel.2026.114666","DOIUrl":"10.1016/j.jconrel.2026.114666","url":null,"abstract":"<div><div>The clinical potential of oral genetically engineered probiotics is widely recognized, which is usually distinguished by the release of expressed active molecules. However, the impact of the release mode of bacterial payloads remains unknown. Here, we propose a novel release mode, “producing and storing first, then responding and releasing”, in a genetically engineered probiotic. Inflammatory bowel disease is a typical chronic intestinal disease, where nitrate in the intestinal route is highly produced. <em>Escherichia coli</em> Nissle 1917 (EcN) was genetically engineered to highly express TNF-α nanobodies (Nb^TNF-α) for storing and releasing in response to nitrate. Two types of release systems were designed: a protein complex secretion machine, Hly system, and a φX174E-based lysis-release system. These systems were separately recombined into EcN as E5 and E7. The expression and strong anti-inflammation activity of Nb^TNF-α from <em>E. coli</em> were first confirmed. A NarX/L sensing system was tailored for nitrate, which was a typical biomarker of intestinal inflammation. Both E5 and E7 exhibited similar <em>in vitro</em> kinetics of Nb^TNF-α secretion. High anti-ulcerative colitis effects were achieved by oral administration of E5 and E7, characterized by inflammation attenuation and recovery of intestinal mucosal barriers, and the levels of Nb^TNF-α expressed by both in the intestinal tract were similar. This work provides new insights into the design of pathological environment-responsive genetically engineered probiotics against diseases.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114666"},"PeriodicalIF":11.5,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071497","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":"Ocular delivery of different valosin-containing protein (VCP) inhibitory formulations prevents retinal degeneration in rho∆I255 mice","authors":"Bowen Cao ,&nbsp;Ana-Cristina Almansa-Garcia ,&nbsp;Merve Sen ,&nbsp;Regine Mühlfriedel ,&nbsp;Mathias W. Seeliger ,&nbsp;Anne-Sophie Petremann-Dumé ,&nbsp;Ellen Kilger ,&nbsp;Anneli Vollert ,&nbsp;Sylvia Bolz ,&nbsp;Christine Henes ,&nbsp;Paolo Caliceti ,&nbsp;Stefano Salmaso ,&nbsp;Marius Ueffing ,&nbsp;Blanca Arango-Gonzalez","doi":"10.1016/j.jconrel.2026.114670","DOIUrl":"10.1016/j.jconrel.2026.114670","url":null,"abstract":"<div><div>Rhodopsin-mediated autosomal dominant retinitis pigmentosa (<em>RHO</em>-adRP) is a progressive inherited retinal degenerative disorder currently lacking effective treatments. A recurrent 3-base pair deletion in the RHO gene, resulting in the loss of isoleucine at codon 255 or 256 (<em>RHO</em>^∆I255 or <em>RHO</em>^∆I256), has been identified in patients from the United Kingdom, Germany, Belgium, China, and Korea, suggesting a broad geographic distribution. This mutation leads to rhodopsin (RHO) misfolding, its retention in the endoplasmic reticulum (ER), and aggregation with wild-type (WT) RHO, ultimately triggering ER stress and photoreceptor degeneration. These aggregates are primarily cleared via the ER-associated degradation (ERAD) pathway, with valosin-containing protein (VCP) playing a key role in their retrotranslocation and proteasomal degradation. Pharmacological or genetic inhibition of VCP has shown neuroprotective effects in other models of adRP, but the poor aqueous solubility of VCP inhibitors and challenges in retinal drug delivery hinder clinical translation.</div><div>To overcome these limitations, we evaluated and compared three VCP-targeted therapeutic strategies in <em>Rho</em>^∆I255 knock-in mouse retinae: (1) small-molecule inhibitors (ML240, NMS-873) solubilized in DMSO, (2) ML240 encapsulated in monomethoxy-polyethylene glycol (mPEG)-cholane nanoparticles, and (3) small interfering RNA (siRNA) targeting VCP, delivered via magnetic nanoparticles. Neuroprotective effects were assessed in vitro in retinal explants and in vivo following intravitreal injection.</div><div>Our findings provide the first evidence that VCP inhibition restores RHO trafficking to the outer segments and prevents photoreceptor cell death in the <em>Rho</em>^∆I255 model. Among the three approaches, nanocarrier-encapsulated ML240 exhibited superior efficacy, enabling sustained drug delivery and enhanced photoreceptor protection. These results establish a preclinical proof-of-concept for nanocarrier-mediated VCP inhibition as a promising therapeutic strategy for <em>RHO</em>-adRP and potentially other ER-stress-related retinal degenerations.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114670"},"PeriodicalIF":11.5,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072206","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":"Long-acting nanomedicine for brain diseases","authors":"Jun Liao ,&nbsp;Qi Huang ,&nbsp;Ruiyu Li ,&nbsp;Lidong Gong ,&nbsp;Tiancheng Li ,&nbsp;Zhiqiang Lin","doi":"10.1016/j.jconrel.2026.114665","DOIUrl":"10.1016/j.jconrel.2026.114665","url":null,"abstract":"<div><div>Effective pharmacological management of neurological disorders is profoundly limited by the blood-brain barrier (BBB) and the short biological half-life of therapeutics, necessitating frequent and invasive administration. Long-acting drug delivery systems (LADDS) integrated with nanotechnology offer a transformative paradigm to overcome these challenges. This review discusses the key principles and nanoplatforms enabling sustained brain drug delivery to the central nervous system. Key release mechanisms are analyzed including diffusion, degradation, and stimuli-responsiveness which alongside a survey of major nanocarrier platforms, designed to achieve controlled pharmacokinetics and enhanced BBB penetration. Recent groundbreaking applications in preclinical models of ischemic stroke, Alzheimer's disease, glioma, and traumatic brain injury are highlighted, where LADDS provide continuous, localized neuroprotection and modulate chronic pathology. Finally, the significant translational challenges, including long-term biocompatibility, manufacturing scalability, and regulatory hurdles, are critically evaluated. LADDS are poised to redefine neuropharmacology, shifting the focus from transient symptom management to precise, durable, and restorative intervention for chronic brain diseases.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114665"},"PeriodicalIF":11.5,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072205","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":"Ultrasmall zwitterion-micelles coupled with anti-checkpoint antibody for overcoming glioma barriers to eliminate stem cells and amplify immunotherapy","authors":"Ke Wang ,&nbsp;Yi Wang ,&nbsp;Dongyu Zhang ,&nbsp;Bingbing Zhao ,&nbsp;Shineng Chen ,&nbsp;Yinan Zhong ,&nbsp;Dechun Huang ,&nbsp;Hongliang Qian ,&nbsp;Hao Xie ,&nbsp;Wei Chen","doi":"10.1016/j.jconrel.2026.114668","DOIUrl":"10.1016/j.jconrel.2026.114668","url":null,"abstract":"<div><div>The efficacy of immune checkpoint blockade (ICB) against glioblastoma (GBM) is significantly constrained by the blood-brain barrier (BBB) and the immunosuppressive tumor microenvironment associated with glioma stem cells (GSCs). To address these challenges, anti-programmed death-ligand 1 antibodies (anti-PD-L1) are conjugated to ultra-small zwitterionic micelles (MCB) through pH-sensitive traceless linkers, followed by encapsulation of salinomycin (SAL) to construct multimodal zwitterionic micelles (MCB-PD@S). The resulting micelles efficiently cross the BBB via BGT-1-mediated active transport, exploit vesicular trafficking pathways in GBM vasculature for tumor-specific accumulation, and utilize their zwitterionic surface to enhance penetration into GSC niches through monocarboxylate transporters (MCTs). SAL-induced eradication of GSCs robustly stimulates immunogenic cell death, dendritic cell maturation, and subsequent T-cell activation. This effect is synergistically amplified by the release of structurally intact anti-PD-L1 within the acidic tumor microenvironment, collectively fostering potent and sustained antitumor immunity that effectively suppresses GBM recurrence. This work establishes a new paradigm in brain tumor therapy by simultaneously overcoming biological delivery barriers and immune evasion, offering a clinically translatable solution for post-resection GBM management.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114668"},"PeriodicalIF":11.5,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072203","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":"Dendritic cell-targeted tumor antigen delivery by glucosylated lipid nanoparticles for precision tumor immunotherapy","authors":"Jing Liu ,&nbsp;Fengyi Lin ,&nbsp;Guanghao Hu ,&nbsp;Ruixin Zhang ,&nbsp;Changyang Gong ,&nbsp;Xun Sun ,&nbsp;Peng Mi","doi":"10.1016/j.jconrel.2026.114671","DOIUrl":"10.1016/j.jconrel.2026.114671","url":null,"abstract":"<div><div>Vaccination is an important approach for cancer immunotherapy, but is limited by the inefficient delivery of immunogenic antigens to dendritic cells (DCs) to stimulate tumor-specific immune responses. Herein, we engineered glucosylated lipid nanoparticles (GluLNPs) to deliver tumor antigens and form personalized vaccines in situ, efficiently targeting DCs to stimulate robust antitumor immunity for the immunotherapy of low-immunogenic breast cancer. Through intratumoral injection, GluLNPs can efficiently capture and deliver tumor antigens, including neoantigens released from eradicated primary triple-negative breast tumors after mild phototherapy with photosensitizer-loaded nanoparticles (i.e., ICGNPs), to DCs, thereby triggering DC maturation and robust antitumor immune responses. Moreover, GluLNPs can effectively elicit strong systemic antitumor immunity against distant and metastatic triple-negative breast tumors when combined with immune checkpoint blockade. This study presents a practical strategy for developing effective DC-targeting personalized nanovaccines and in situ vaccination for precise and effective tumor immunotherapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114671"},"PeriodicalIF":11.5,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072204","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":"Macrophage membrane-biomimetic DNA nanocages deliver taurine to reprogram trained immunity for periodontitis therapy","authors":"Ya Cui ,&nbsp;Xiaojing Li ,&nbsp;Shebin Hong ,&nbsp;Kaili Lin ,&nbsp;Lixia Mao ,&nbsp;Xudong Wang","doi":"10.1016/j.jconrel.2026.114664","DOIUrl":"10.1016/j.jconrel.2026.114664","url":null,"abstract":"<div><div>As one of the most burdensome oral diseases, periodontitis frequently leads to tooth loss and heightens the risk of systemic diseases. A major clinical challenge is that current strategies often fail to resolve chronic inflammation and bone resorption characteristic of its refractory state. Recent research implicates maladaptive trained immunity (TRIM) as a core mechanism, which promotes myeloid cell skewing and amplifies inflammatory responses and bone loss. Single-cell sequencing of peripheral blood mononuclear cells from periodontitis patients identified an elevated inflammatory stress state. Taurine, a sulfur-containing amino acid with known anti-inflammatory properties, offers therapeutic potential, but its application is limited by low oral bioavailability and a lack of target specificity. To address these challenges, a novel therapeutic strategy based on precisely engineered DNA nanocages carrying taurine has been developed. These nanocages are camouflaged with hybrid cell membranes harvested from M2-polarized and trained-immunosuppressive macrophages for targeted monocytes. This biomimetic system is designed to therapeutically correct the dysregulated TRIM state in monocytes and macrophages, effectively inhibiting inflammation and bone destruction. Concurrently, it restores the osteogenic differentiation and mitochondrial function of periodontal ligament cells via immune modulation, establishing a novel strategy for the precise immunotherapy of chronic periodontitis.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114664"},"PeriodicalIF":11.5,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048493","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 proimmunotoxin nanodrug targeting AIDS-associated non-Hodgkin lymphoma","authors":"Shilin Chen ,&nbsp;Tong Qi ,&nbsp;Hongxu Peng ,&nbsp;Eugene Kimura ,&nbsp;Xiang Zhang ,&nbsp;Emiko Kranz ,&nbsp;Zheng Cao ,&nbsp;Zi Wang ,&nbsp;Wenting Chen ,&nbsp;Leonardo R. Ancheta ,&nbsp;Douglas A. Lappi ,&nbsp;Pei-Yu Chiou ,&nbsp;Yunfeng Lu ,&nbsp;Tracy R. Daniels-Wells ,&nbsp;Manuel L. Penichet ,&nbsp;Jing Wen","doi":"10.1016/j.jconrel.2026.114661","DOIUrl":"10.1016/j.jconrel.2026.114661","url":null,"abstract":"<div><div>B-cell non-Hodgkin lymphoma (NHL) is the most common hematopoietic malignancy in the United States, with a notably higher incidence and aggressiveness observed in individuals infected with human immunodeficiency virus (HIV), leading to AIDS-associated NHL (AIDS-NHL). The transferrin receptor 1 (TfR1/CD71), a type II transmembrane homodimeric protein, is overexpressed on several cancers, including NHL, providing a meaningful therapeutic target. Our group developed an anti-TfR1 IgG3-avidin fusion protein, ch128.1Av, designed to deliver biotinylated therapeutic agents into cancer cells through receptor-mediated endocytosis. When coupled with biotinylated saporin 6 (b-SO6), a plant-derived protein synthesis inhibitor, the resulting ch128.1Av/b-SO6 immunotoxin is highly effective at killing malignant cells. However, toxicity to normal cells limits its systemic administration. To overcome this problem, we developed a proimmunotoxin nanodrug, named “n(ch128.1Av/b-SO6)-CXCL13”. This strategy involves encapsulating individual immunotoxins within a thin zwitterionic polymer shell, which is stabilized by peptide crosslinkers that only respond to metalloproteinase-2 (MMP-2), a tumor microenvironment-specific enzyme. The nanodrug is further conjugated with a B-cell targeting chemokine CXCL13. This design allows the proimmunotoxin to circulate safely, specifically accumulate and release encapsulated ch128.1Av/b-SO6 intratumorally in response to MMP-2. This approach not only minimizes off-target toxicity but also enhances tissue penetration by enabling choline analogues on proimmunotoxin nanodrugs to bind choline transporters expressed on tumor cells or the blood-brain barrier. Importantly, n(ch128.1Av/b-SO6)-CXCL13 demonstrated antitumor efficacy in an AIDS-associated NHL xenograft mouse model. Taken together, our results suggest that n(ch128.1Av/b-SO6)-CXCL13, or similar proimmunotoxin strategies, represents a promising therapeutic avenue for AIDS-NHL and potentially other malignancies.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114661"},"PeriodicalIF":11.5,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048494","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-PD-L1 biomimetic nanobubbles for ultrasound-triggered reprogramming of cold hepatocellular carcinoma for immunotherapy","authors":"Haibin Tu ,&nbsp;Yanbing Cao ,&nbsp;Xinyi Lin ,&nbsp;Lei Ding ,&nbsp;Yang Zhou ,&nbsp;Siyi Feng ,&nbsp;Xiaolong Liu ,&nbsp;Ming Wu","doi":"10.1016/j.jconrel.2026.114659","DOIUrl":"10.1016/j.jconrel.2026.114659","url":null,"abstract":"<div><div>Hepatocellular carcinoma exhibits profound resistance to immune checkpoint blockade due to its dense stromal architecture and immunosuppressive tumor microenvironment with an immune-excluded phenotype. To overcome this therapeutic challenge, we developed PD-1-displaying biomimetic nanobubbles (NB@CM-H-PD-1) that orchestrate a trimodal strategy combining PD-L1-targeted checkpoint blockade, sonodynamic therapy, and acoustic cavitation-mediated stromal remodeling to transform immunologically “cold” HCC into an immune-responsive state. These engineered nanobubbles comprise a perfluorocarbon core, a lipid-bilayer shell embedded with hematoporphyrin monomethyl ether, and an outer coating of cell membranes derived from PD-1–overexpressing cells. The platform executes a synchronized cascade: membrane-displayed PD-1 mediates tumor-specific targeting while providing checkpoint inhibition; sonosensitizer activation generates reactive oxygen species (ROS) triggering immunogenic cell death; and ultrasound-targeted nanobubble destruction enhances intratumoral penetration through cavitation-induced stromal disruption. In vitro characterization demonstrated that NB@CM-H-PD-1 maintained excellent biocompatibility under physiological conditions while exhibiting potent ultrasound-triggered ROS production and cytotoxic activity. In both subcutaneous and metastatic HCC models, this approach achieved near-complete tumor eradication without systemic toxicity. Comprehensive immunological analyses revealed robust immunogenic cell death induction, dendritic cells (DCs) maturation, enhanced T-cell infiltration with increased IFN-γ secretion, and tumor microenvironment reprogramming that initiated systemic antitumor immunity controlling both primary and metastatic lesions. Thus, our findings establish this biomimetic platform as an effective mechano-chemical-immune synergistic actuator for sensitizing refractory HCC to immunotherapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114659"},"PeriodicalIF":11.5,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048495","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":"pH-responsive polymeric-peptide complex enhances tumor immunogenic cell death by membrane disruption","authors":"Guanyu Jin ,&nbsp;Zhaofan Yang ,&nbsp;Lanqing Wang ,&nbsp;Shucheng Zhang ,&nbsp;Shanyi Lin ,&nbsp;Zhuoling Bi ,&nbsp;Bingzheng Yu ,&nbsp;Yuanzhen Su ,&nbsp;Sijun Xiang ,&nbsp;Irina A. Veselova ,&nbsp;Hao Liu ,&nbsp;Fangda Li ,&nbsp;Shuilin Wu ,&nbsp;Mingqiang Li ,&nbsp;Xuesi Chen ,&nbsp;Shixian Lv","doi":"10.1016/j.jconrel.2026.114660","DOIUrl":"10.1016/j.jconrel.2026.114660","url":null,"abstract":"<div><div>Melittin, the principal bioactive component of bee venom, exhibits potent anticancer activity. However, its clinical application is hindered by nonspecific hemolytic toxicity. In this study, we developed a pH-responsive polymeric-peptide complex (PCM) to improve anti-tumor activity of melittin while minimizing off-target effects. PCM remained structurally stable under physiological conditions (pH 7.4) but underwent rapid disassembly in the mildly acidic tumor microenvironment (pH 6.8) to expose melittin. The exposed melittin bound to tumor cell membranes, compromised membrane integrity through transmembrane pore formation, leading to tumor cell death. This membrane disruption elicited the release of damage-associated molecular patterns, thereby activating antitumor immune responses. In a murine breast cancer model, low dose administration of PCM significantly inhibited tumor recurrence and metastasis, and generated durable antitumor immunological memory without significant side effects. The mechanistic actions and morphological effects of PCM on tumor cells were thoroughly investigated, providing important theoretical insights for the clinical translation of anticancer peptides.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114660"},"PeriodicalIF":11.5,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048496","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}