Journal of Controlled Release最新文献

{"title":"Ultraviolet-tyrosinase cascade caged antisense oligonucleotide for precise treatment of hyperpigmentation","authors":"Li Zhou ,&nbsp;Fangfang Duan ,&nbsp;Yuting Zhang ,&nbsp;Yicai Huang ,&nbsp;Le Xu ,&nbsp;Nan Zhang ,&nbsp;Shiming Yang ,&nbsp;Yi Ma ,&nbsp;Bing Yang ,&nbsp;Kai Lu","doi":"10.1016/j.jconrel.2025.114233","DOIUrl":"10.1016/j.jconrel.2025.114233","url":null,"abstract":"<div><div>Hyperpigmentation is a skin disorder characterized by the abnormal accumulation of melanin, in which the melanocortin-1 receptor (MC1R) was recognized as a key target for melanin production. Antisense oligonucleotide (ASO), by targeting mRNA to inhibit protein synthesis, holds a promising gene therapy for hyperpigmentation. However, challenges such as nonspecific activation, off-target toxicity, and limited cellular permeability hinder their broader clinical application. Inspired by the Chinese proverb “Turn an enemy into a friend”, we introduce a dual-gated, ultraviolet (UV)-tyrosinase (TYR) cascade-responsive modified ASO (m-ASO) that enables spatiotemporally controlled silencing of MC1R. The engineered m-ASO is caged via thymidine modification, rendering it inactive until sequentially exposed to exogenous UV and intracellular TYR. UV irradiation, conventionally hyperpigmentation trigger, is repurposed to initiate decaging of m-ASO into an intermediate form, ph-ASO. This intermediate is then enzymatically activated by TYR overexpressed in melanocytes within pigmented tissues, ultimately restoring the native conformation and therapeutic function of the ASO. This “enemy-to-ally” strategy allows for disease-specific, precision activation of ASO therapeutics. Notably, to enhance transdermal delivery, the m-ASO nanocomplex is integrated into a biocompatible, dissolvable microneedle system for painless and localized epidermal administration. The resulting platform demonstrates precise MC1R silencing and effective melanin suppression, while sparing normal melanocytes. Together, this cascade-caged, cell-selective, and minimally invasive strategy presents a novel framework for programmable nucleic acid therapeutics in dermatological and enzyme-overexpressing diseases.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114233"},"PeriodicalIF":11.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043379","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":"Sono-triggered nanoamplifier mediates ferroptosis-immune regulation against bacterial pneumonia","authors":"Zhen-Zhen Wang ,&nbsp;Ruan-Ting Bei ,&nbsp;Hao-Hang Xu ,&nbsp;Ling-Feng Xu ,&nbsp;Xiao-Tong Sun ,&nbsp;Tong Ye ,&nbsp;Lu-Lu Wang ,&nbsp;Can Wu ,&nbsp;Xuan Wu ,&nbsp;Ming-San Miao ,&nbsp;Xin Pang","doi":"10.1016/j.jconrel.2025.114234","DOIUrl":"10.1016/j.jconrel.2025.114234","url":null,"abstract":"<div><div>In the post-pandemic era, multidrug-resistant (MDR) bacterial pneumonia has become a critical global health challenge due to its frequent evasion of conventional antibiotic therapies. Redox metabolic regulation therapy (RMRT), which targets pathological cells through reactive oxygen species (ROS)-mediated disruption of redox homeostasis, has emerged as a promising antibiotic-free approach with broad-spectrum efficacy and reduced resistance potential. In this study, we surprisingly discovered that tirapazamine (TPZ), a clinical hypoxia-activated anticancer prodrug, exhibits potent bacterial ferroptosis-inducing capability via multimodal metabolic interference, suggesting its repurposing potential for pneumonia treatment. To overcome pulmonary delivery limitations and enhance therapeutic performance, a self-reinforcing RMRT amplifier was engineered through supramolecular co-assembly of repurposed TPZ with natural sonosensitizer purpurin 18 (P18). Ultrasound-triggered P18 not only generates bactericidal ROS but also exacerbates infection-site hypoxia, thereby activating TPZ to initiate a ferroptosis cascade via dual mechanisms: ROS overproduction through hypoxia-specific bioactivation and extracellular Fe²⁺ influx potentiation. Notably, the resulting ferroptotic bacteria function as endogenous immunostimulants, subsequently trigger a cascade of immunological responses to establish an antimicrobial-favorable microenvironment. Such RMRT nanoamplifier presents a safe, efficient, and easily accessible strategy that synergizes ferroptosis-associated metabolic regulation and immune activation to combat MDR bacterial pneumonia.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114234"},"PeriodicalIF":11.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043377","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":"Dual STING activation and CD47/SIRPα blockade via chitooligosaccharide-based nanoparticles to amplify antitumor immunity","authors":"Shaohui Xu ,&nbsp;Jiahan Shao ,&nbsp;Zhijun Miao ,&nbsp;Heng Wang ,&nbsp;Huaxing Dai ,&nbsp;Bo Tian ,&nbsp;Run Shi ,&nbsp;Yinan Zhong ,&nbsp;Chao Wang","doi":"10.1016/j.jconrel.2025.114235","DOIUrl":"10.1016/j.jconrel.2025.114235","url":null,"abstract":"<div><div>The stimulator of interferon genes (STING) pathway represents a promising target for cancer immunotherapy, but traditional small-molecule agonists suffer from poor pharmacokinetics and systemic toxicity. To address this, we engineered chitooligosaccharide (COS)-dendritic polycarbonate (DPC) nanoparticles (CD NPs) as polymeric STING agonists with enhanced stability and tumor retention. Compared with free COS, CD NPs induced ∼5–7-fold higher <em>Ifnb1</em> and <em>Cxcl10</em> expression, robustly activated TBK1/IRF3 phosphorylation, and strengthened STING signaling in macrophages and tumor cells. In vivo, CD NPs selectively accumulated in tumors, increased M1 macrophages and dendritic cell maturation, reduced myeloid-derived suppressor cells, and promoted CD8+ T-cell infiltration, thereby reshaping the tumor microenvironment into a pro-inflammatory state. To further counter immune evasion, we encapsulated the CD47/SIRPα inhibitor RRX-001 into reactive oxygen species (ROS)-responsive carriers, yielding RRX@RCD. This dual-modality platform blocked the “don't eat me” signal while amplifying STING signaling, markedly enhancing tumor cell phagocytosis and interferon production. In CT26 tumor-bearing mice, RRX@RCD achieved superior tumor regression, doubled median survival. Overall, RRX@RCD synchronizes innate and adaptive immune activation, offering a safe and potent nanomedicine strategy for durable antitumor immunity.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114235"},"PeriodicalIF":11.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043387","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":"Vascular endothelial cell-targeted mRNA delivery via synthetic lipid nanoparticles for venous thrombosis prevention","authors":"Zhiwei Guo, Lianfeng Fan, Yinyu Ma, Kaisong Tian, Wei Qiu, Anqi Wei, Wei Fu, Yuanyuan Chen, Zhiping Cui, Songli Wang, Changyou Zhan","doi":"10.1016/j.jconrel.2025.114147","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.114147","url":null,"abstract":"Venous thromboembolism significantly contributes to the global disease burden. Anticoagulant and antiplatelet therapies are currently the treatment strategies. However, challenges remain due to hemorrhagic complications and the inability to resolve established thrombi. There is an urgent need for a new generation of antithrombotic agents. Given the fibrin specificity and rapid thrombus dissolution capacity of recombinant tissue plasminogen activator (TPA) protein, along with the significant advantages of mRNA therapeutics in protein replacement, we aim to develop an antithrombotic strategy through the targeted delivery of TPA mRNA to vascular endothelial cells using synthetic lipid nanoparticles (LNPs). A series of amino ionizable lipids were synthesized to create an LNP library, from which the LNP selectively targeting vascular endothelial cells (vtLNP) was selected by a DNA barcode labeling high-throughput screening method. The antithrombotic efficacy and safety of vtLNP loaded with TPA mRNA (vtLNP@TPA) were evaluated in a deep vein thrombosis (DVT) mouse model and normal ICR mice, respectively. The results revealed that vtLNP@TPA significantly prevented the occurrence and development of venous thrombosis. This study provides relevant experimental evidence for a novel antithrombotic therapy strategy for venous thrombosis using mRNA therapeutics.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"28 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043378","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":"Bilayer self-assembly encapsulated by engineered vesicle disrupts glutathione to induce Disulfidptosis-enhanced cuproptosis for tumor immunotherapy","authors":"Yuqi Cao ,&nbsp;Xiaomin Zhao ,&nbsp;Yuhang Miao ,&nbsp;Xinhe Liu,&nbsp;Xin Liu,&nbsp;Zongxin Yue,&nbsp;Xin Ruan,&nbsp;Qiannan Tu,&nbsp;Xin Wang,&nbsp;Guoliang Zhou,&nbsp;Jia Hu,&nbsp;Dawei Deng","doi":"10.1016/j.jconrel.2025.114232","DOIUrl":"10.1016/j.jconrel.2025.114232","url":null,"abstract":"<div><div>Cuproptosis, a copper-dependent programmed cell death, can effectively activate tumor immunogenicity and reverse the immunosuppressive tumor microenvironment (TME). Nevertheless, the overexpression of xCT-SLC7A11 in tumor cells is beneficial for maintaining the biosynthesis of glutathione (GSH) to counteract cuproptosis. Herein, copper-based bilayer self-assembly Cel-Cu/DHA (CCD) encapsulated by red blood cell vesicle engineered with folate (RF), CCD@RF nanoparticles (NPs), have been prepared to target synergistic therapeutic mechanisms and induce disulfidptosis-enhanced cuproptosis for augmented anti-tumor immunotherapy by disrupting intracellular GSH balance. In xCT-SLC7A11^high cancer cells, dihydroartemisinin (DHA) pre-released from CCD@RF NPs serves to impede glucose metabolism, thereby downregulating NADPH levels, causing the accumulation of cystine and the collapse of actin cytoskeleton proteins. This simultaneously induces disulfidptosis and blocks the source of cysteine which is essential for GSH synthesis, thereby amplifying cuproptosis with assistance of celastrol (Cel). Moreover, Cu²⁺ released from CCD@RF NPs, once reduced by GSH, could catalyze Fenton-like reactions to generate hydroxyl radicals (·OH), further disrupting intracellular redox homeostasis. Tumor cells undergoing immunogenic cell death (ICD) derived from disulfidptosis-enhanced cuproptosis, could release antigens, inducing robust immune responses, ultimately effectively inhibiting tumor growth and metastasis. This work proposes a novel dual-pronged therapeutic strategy by disrupting intracellular redox balance, offering a new direction for future anti-tumor immunotherapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114232"},"PeriodicalIF":11.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043127","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":"Alkaline phosphatase-responsive hydrogel for efficient management of autoimmune intraocular inflammation","authors":"Yijing Li ,&nbsp;Dan Lin ,&nbsp;Jinrun Chen ,&nbsp;Wenqiao Zhang ,&nbsp;Huanting Jin ,&nbsp;Shuqi Feng ,&nbsp;Huanyu Mao ,&nbsp;Jiabei Hou ,&nbsp;Xingyi Li ,&nbsp;Yuqin Wang ,&nbsp;Jianhong Zhou","doi":"10.1016/j.jconrel.2025.114229","DOIUrl":"10.1016/j.jconrel.2025.114229","url":null,"abstract":"<div><div>Autoimmune uveitis (AU) remains a leading cause of visual impairment and blindness worldwide, necessitating efficient and innovative therapeutic strategies to overcome the limitations of current clinical interventions. Capitalizing on the significant elevation of alkaline phosphatase (ALP) levels in intraocular tissues (vitreous humor, retina) during AU pathogenesis, we rationally designed an ALP-responsive self-delivering dexamethasone sodium phosphate (DexP) hydrogel using an ionic cross-linking approach. This DexP hydrogel serves as a sustained-release depot for adalimumab (ADA), enabling synergetic AU therapy through a simple combination of aqueous DexP and ADA solutions with calcium chloride under mild conditions, which facilitates controlled release of both therapeutics in an ALP-responsive manner. Importantly, <em>in vivo</em> experiments demonstrated that a single intravitreal (IVT) injection of ADA@DexP hydrogel significantly attenuated autoimmune intraocular inflammation by effectively inhibiting inflammatory cell infiltration, suppressing pro-inflammatory cytokines (IL-17A, IL-1β, TNF-α), and preserving blood-retinal barrier (BRB) integrity. Furthermore, the intravitreal administration of ADA@DexP hydrogel exhibited excellent intraocular biocompatibility and a safety profile. Overall, this carrier-free ADA@DexP hydrogel represents a promising alternative strategy for AU therapy, particularly given that both DexP and ADA are FDA-approved clinical agents.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114229"},"PeriodicalIF":11.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043194","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":"Intravenous lipid-siRNA conjugate mediates gene silencing at the blood-brain barrier and blood-CSF barrier","authors":"Alexander G. Sorets ,&nbsp;Katrina R. Schwensen ,&nbsp;Nora Francini ,&nbsp;Andrew Kjar ,&nbsp;Sarah Lyons ,&nbsp;Joshua C. Park ,&nbsp;Dillon Palmer ,&nbsp;Adam M. Abdulrahman ,&nbsp;Rebecca P. Cowell ,&nbsp;Ketaki A. Katdare ,&nbsp;Ella N. Hoogenboezem ,&nbsp;Angela Wang ,&nbsp;Alexander P. Ligocki ,&nbsp;Rebecca J. Embalabala ,&nbsp;Neil Dani ,&nbsp;Craig L. Duvall ,&nbsp;Ethan S. Lippmann","doi":"10.1016/j.jconrel.2025.114226","DOIUrl":"10.1016/j.jconrel.2025.114226","url":null,"abstract":"<div><div>Barriers of the central nervous system (CNS), such as the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), regulate the two-way exchange of material between the blood and CNS. While the BBB and BCSFB can become dysfunctional in patients with chronic CNS diseases, few studies have focused on strategies for targeting these interfaces. Here, we showed that an intravenously administered lipid-siRNA conjugate was delivered to and silenced genes within brain endothelial cells and choroid plexus epithelial cells, which comprise the BBB and BCSFB, respectively. A single intravenous dose of lipid-siRNA conjugate was delivered to ∼100 % of brain endothelial cells and major choroid plexus cell types, without substantial delivery into brain parenchymal tissue. Sustained mRNA and protein silencing was achieved in both brain endothelial cells and bulk choroid plexus tissues. Moreover, single cell RNA sequencing demonstrated gene knockdown in capillaries, venous endothelial cells, and choroid plexus epithelial cells without silencing genes in parenchymal cell populations. Collectively, this work establishes an effective nonviral framework to mediate gene inhibition in the brain barriers.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114226"},"PeriodicalIF":11.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043383","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 forming silk fibroin hydrogel dressing accelerates acute wound healing via immunomodulation and extracellular matrix regeneration","authors":"Zhiyang Chen ,&nbsp;Jialing Cheng ,&nbsp;Mo Wang ,&nbsp;Yu Jiang ,&nbsp;Dengbao Jiang ,&nbsp;Yanfang Yang ,&nbsp;Yanjing Bai ,&nbsp;Lingshuang Wang ,&nbsp;Caili Ma ,&nbsp;Jun Ye ,&nbsp;Hongliang Wang ,&nbsp;Yulin Liu","doi":"10.1016/j.jconrel.2025.114228","DOIUrl":"10.1016/j.jconrel.2025.114228","url":null,"abstract":"<div><div>Cutaneous injuries, a prevalent clinical challenge, often face delayed healing due to suboptimal wound management strategies. Conventional hydrogel dressings are limited by inadequate mechanical properties, poor bioactivity, and insufficient therapeutic efficacy. Here, we developed an innovative in situ forming hydrogel dressing by integrating silk fibroin (SF)—a natural biopolymer with tunable structural and bioactive properties—with polyvinyl butyral (PVB), which provides an ideal system for the delivery of active substances for wound healing and has broad application prospects in skin wound management. Upon ethanol evaporation, the SF/PVB composite rapidly formed a hydrogel film with enhanced mechanical strength, optimal breathability, and waterproofness. The SF-based dressing (LD-SF) demonstrated multifunctional wound-healing capabilities, including rapid hemostasis, antioxidative activity, and anti-inflammatory modulation. Notably, molecular-weight (MW)-dependent bioactivity was observed: low-MW SF (45 kDa) significantly promoted fibroblast proliferation and migration, while high-MW SF (72 kDa) exhibited superior immunomodulatory effects by polarizing macrophages toward pro-resolving phenotypes. In a murine full-thickness wound model, LD-SF accelerated re-epithelialization, enhanced angiogenesis, and stimulated collagen remodeling. Mechanistically, LD-SF facilitated extracellular matrix regeneration via <em>β</em>-sheet-driven structural stability and amino acid-mediated metabolic support. This dual-action system synergistically orchestrates immunomodulation—through macrophage phenotype regulation and cytokine balance—and robust extracellular matrix regeneration, offering a transformative approach to acute wound repair with minimized scarring and accelerated functional recovery. The study provides a clinically translatable solution for acute wound care by integrating rapid in situ film formation, molecular-weight-tunable bioactivity, and scar-minimizing outcomes, thereby addressing critical gaps in current wound management technologies.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114228"},"PeriodicalIF":11.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043381","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":"Endoplasmic reticulum-mitochondria dual-targeting nanoplatform suppresses cancer stemness and enhances colorectal cancer immunotherapy","authors":"Yilin Wang ,&nbsp;Wenting Cheng ,&nbsp;Yang Chen ,&nbsp;Hailong Tian ,&nbsp;Canhua Huang ,&nbsp;Ka Li","doi":"10.1016/j.jconrel.2025.114230","DOIUrl":"10.1016/j.jconrel.2025.114230","url":null,"abstract":"<div><div>Cancer stemness in colorectal cancer (CRC) drives immune evasion and fosters an immunosuppressive tumor microenvironment (TME), limiting the efficacy of immunotherapy. To counteract this stemness-driven immune evasion, we developed a hyaluronic acid (HA) surface-modified dual-targeting nanoplatform (HA/pCe6-Ato NPs) that induces both endoplasmic reticulum stress and mitochondrial dysfunction. HA functionalization facilitates tumor-specific targeting via CD44 receptor-mediated endocytosis. The nanoplatform incorporates an ER-targeting photosensitizer, pCe6, synthesized by conjugating Chlorin e6 with p-Toluenesulfonamide, and the mitochondrial respiratory chain inhibitor atovaquone (Ato), which self-assembles into nanoparticles. Upon activation, HA/pCe6-Ato NPs induce ER stress and mitochondrial dysfunction, disrupting cancer stemness and reprogramming the immunosuppressive TME. Preclinical evaluations showed that HA/pCe6-Ato NPs promote apoptosis and accelerate reactive oxygen species production in cancer stem-like cells (CSCs), while reducing immunosuppressive factor secretion and enhancing immune effector cell infiltration. These effects synergistically enhance the efficacy of immunotherapy, achieving superior tumor inhibition compared with conventional monotherapies. Collectively, HA/pCe6-Ato NPs highlight the potential of organelle-targeting strategies to dismantle cancer resilience mechanisms, providing a foundation for dual-targeting nanomedicines to overcome resistance and enhance immunotherapy in CRC.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114230"},"PeriodicalIF":11.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043727","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":"Balloon-like polymersomes with tunable charged and burstable interfaces for controlled drug delivery","authors":"Gang Zhang ,&nbsp;Zifen Li ,&nbsp;Rongrong Zou,&nbsp;Rui Yang,&nbsp;Zuojie Wang,&nbsp;Yi Zheng,&nbsp;Yeqiang Zhou,&nbsp;Xiaobing Ma,&nbsp;Yang Liu,&nbsp;Hong Tan,&nbsp;Mingming Ding","doi":"10.1016/j.jconrel.2025.114227","DOIUrl":"10.1016/j.jconrel.2025.114227","url":null,"abstract":"<div><div>Inherent instability, low response efficiency, and lack of functionality have hindered the clinical application of polymer drug carriers. Addressing these challenges through straightforward molecular design remains a significant obstacle. Here, we introduce a novel approach using a structurally simple, clickable amphiphilic diblock copolymer vesicle. Our strategy involves asymmetric functionalized interfacial crosslinking, which modifies the interfacial curvature to induce polymersome swelling and stabilizes this metastable state through a disulfide-bond-crosslinked network, reminiscent of an inflated balloon. Moreover, the side chain functional groups of the crosslinking agent provide the self-assembled structures with controllable and switchable surface charges. This feature allows for the manipulation of nanoparticle internalization pathways, tissue distribution and tumor targeting efficacy in vivo. Notably, these functionalized balloon-like polymersomes can burst rapidly under the stimulation of glutathione, thereby facilitating efficient and specific intracellular drug release. This study presents an effective solution to the longstanding dilemma of stability, release, and functionality in diblock copolymer carriers, paving the way for the development of intelligent drug carriers with significant clinical translation potential.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"387 ","pages":"Article 114227"},"PeriodicalIF":11.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043385","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}