Journal of Controlled Release最新文献_第8页

Bioinspired programmed antibiofilm strategies for accelerated wound healing via spatiotemporally controlled enzyme nanoreactors

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-03-01 DOI: 10.1016/j.jconrel.2025.113582

Juntao Hu , Yibing Huang , Hao Hao , Pujing Tian , Yinuo Yin , Yuting He , Fengjie Hao , Wantong Jiang , Yanping Zhang , Youzhong Wan , Quan Luo

{"title":"Bioinspired programmed antibiofilm strategies for accelerated wound healing via spatiotemporally controlled enzyme nanoreactors","authors":"Juntao Hu , Yibing Huang , Hao Hao , Pujing Tian , Yinuo Yin , Yuting He , Fengjie Hao , Wantong Jiang , Yanping Zhang , Youzhong Wan , Quan Luo","doi":"10.1016/j.jconrel.2025.113582","DOIUrl":"10.1016/j.jconrel.2025.113582","url":null,"abstract":"<div><h3>Abstract</h3><div>Biofilms, protected by their dense, self-produced matrix, pose a significant clinical challenge due to their antibiotic resistance, leading to persistent infections and delayed wound healing, particularly in diabetic patients. Tailored to the biofilm life cycle, a double-layered nanoreactor was developed for rapid and complete antibiofilm therapy. The inner layer, cross-linked with poly(allylamine hydrochloride) (PAH)/phosphate, dimeric indocyanine green (dICG), and bromothymol blue (BTB), shields glucose oxidase (GOx) and β-glucanase (β-DEX) from unfavorable environment. The outer layer is coated with bacteria-targeted gold nanozymes (AuNEs). The healing of biofilm-infected diabetic wounds progresses three spatiotemporal stages activated by light irradiation and pH changes. Initially, the photothermal effect of dICG triggers nitric oxide (NO)-mediated biofilm dispersion and lowers the wound pH via a GOx/AuNEs cascade reaction. The resulting acidic environment then induces nanoreactor disassembly, releasing β-DEX to degrade the biofilm matrix and facilitate deeper penetration. Finally, AuNEs specifically recognize and eliminate planktonic bacteria, further disrupting the biofilms and accelerating wound healing by generating reactive oxygen species (ROS) and more toxic reactive nitrogen species (RNS). The wound status can be monitored in real-time using BTB's colorimetric pH analysis for visual feedback on treatment progress. This multifunctional design offers a programmed antibiofilm strategy for dynamic wound management.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113582"},"PeriodicalIF":10.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526121","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}

引用次数: 0

Pancreas-targeted lipid nanoparticles for relatively non-invasive interleukin-12 mRNA therapy in orthotopic pancreatic ductal adenocarcinoma

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-03-01 DOI: 10.1016/j.jconrel.2025.113588

Qian Shen , Jia Liu , Ling Zeng , Yupeng Ren , Jing Liao , Sijie Chen , Yingsen Tang , Zixi Zhang , Meng Jiang , Hangping Liao , Lingyun Wang , Xiaoding Xu , Jinjin Chen

{"title":"Pancreas-targeted lipid nanoparticles for relatively non-invasive interleukin-12 mRNA therapy in orthotopic pancreatic ductal adenocarcinoma","authors":"Qian Shen , Jia Liu , Ling Zeng , Yupeng Ren , Jing Liao , Sijie Chen , Yingsen Tang , Zixi Zhang , Meng Jiang , Hangping Liao , Lingyun Wang , Xiaoding Xu , Jinjin Chen","doi":"10.1016/j.jconrel.2025.113588","DOIUrl":"10.1016/j.jconrel.2025.113588","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) represents 90 % of pancreatic cancers and shows limited response to immune therapy owing to the highly immunosuppressive tumor microenvironment (TME). Cytokine-encoded mRNA therapy demonstrates a great promise in converting “cold” tumors into “hot” ones, while it is typically administered through intratumoral injection and applicable only to superficial tumors, which limites their application in PDAC. In this study, we design and develop a lipid nanoparticle (LNP) delivery system capable of targeting pancreatic tissue <em>via</em> intraperitoneal (I.P.) injection. This system not only efficiently delivers mRNA to pancreatic tissues but also selectively targets immune cells in PDAC. A single I.P. injection of LNP encapsulating interleukin-12 (IL-12) mRNA (LNP/mIL-12) activates both myeloid and lymphoid cells in PDAC, reprogramming the immunosuppressive TME. Remarkably, I.P. injection of LNP/mIL-12 induces eradication of orthotopic PDAC in some cases. Our work represents the first relatively non-invasive method to deliver IL-12 mRNA for targeted treatment of orthotopic PDAC, offering a novel approach for PDAC immunotherapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113588"},"PeriodicalIF":10.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526087","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}

引用次数: 0

Single-cell technology for cell-based drug delivery and pharmaceutical research

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-03-01 DOI: 10.1016/j.jconrel.2025.113587

Huihui Hu , Yunlong Fan , Jiawen Wang , Jialu Zhang , Yidan Lyu , Xiaoqi Hou , Jizhai Cui , Yamin Zhang , Jianqing Gao , Tianyuan Zhang , Kewang Nan

{"title":"Single-cell technology for cell-based drug delivery and pharmaceutical research","authors":"Huihui Hu , Yunlong Fan , Jiawen Wang , Jialu Zhang , Yidan Lyu , Xiaoqi Hou , Jizhai Cui , Yamin Zhang , Jianqing Gao , Tianyuan Zhang , Kewang Nan","doi":"10.1016/j.jconrel.2025.113587","DOIUrl":"10.1016/j.jconrel.2025.113587","url":null,"abstract":"<div><div>Leveraging the capacity to precisely manipulate and analyze individual cells, single-cell technology has rapidly become an indispensable tool in the advancement of cell-based drug delivery systems and innovative cell therapies. This technology offers powerful means to address cellular heterogeneity and significantly enhance therapeutic efficacy. Recent breakthroughs in techniques such as single-cell electroporation, mechanical perforation, and encapsulation, particularly when integrated with microfluidics and bioelectronics, have led to remarkable improvements in drug delivery efficiency, reductions in cytotoxicity, and more precise targeting of therapeutic effects. Moreover, single-cell analyses, including advanced sequencing and high-resolution sensing, offer profound insights into complex disease mechanisms, the development of drug resistance, and the intricate processes of stem cell differentiation. This review summarizes the most significant applications of these single-cell technologies, highlighting their impact on the landscape of modern biomedicine. Furthermore, it provides a forward-looking perspective on future research directions aimed at further optimizing drug delivery strategies and enhancing therapeutic outcomes in the treatment of various diseases.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113587"},"PeriodicalIF":10.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526122","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}

引用次数: 0

Injectable multifunctional hydrogels for adipose tissue remodeling to treat obesity and alleviate metabolic syndrome

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-03-01 DOI: 10.1016/j.jconrel.2025.113585

Jian-Hua Yan , Pei-Ling Hao , Si-Min Zeng , Chun-Xiao Liang , Yu Chen , Ke-Wei Chen , Wen-Qiang Qu , Xuan Zeng , Zhenlin Zhong , Xian-Zheng Zhang

{"title":"Injectable multifunctional hydrogels for adipose tissue remodeling to treat obesity and alleviate metabolic syndrome","authors":"Jian-Hua Yan , Pei-Ling Hao , Si-Min Zeng , Chun-Xiao Liang , Yu Chen , Ke-Wei Chen , Wen-Qiang Qu , Xuan Zeng , Zhenlin Zhong , Xian-Zheng Zhang","doi":"10.1016/j.jconrel.2025.113585","DOIUrl":"10.1016/j.jconrel.2025.113585","url":null,"abstract":"<div><div>Dysfunction of adipose tissue in obese individuals is associated with metabolic imbalances. Current treatments focus on reducing calorie intake and increasing exercise but have unsatisfactory efficacy and significant side effects. Here, a subcutaneously in situ formed therapeutic hydrogel (RL lip@gel) that can simultaneously modulate the inflammatory environment of adipose tissue and induce adipocyte browning is developed to combat obesity. The alginate solution encapsulates the anti-inflammatory natural flavonoid luteolin and rosiglitazone-loaded liposomes (RL lip), which can be formed as an in situ hydrogel through crosslinking with divalent metal ions in adipose tissue following subcutaneous injection. RL lip@gel not only reprograms M1-like adipose tissue macrophages into an M2-like phenotype but diminishes the expression of proinflammatory cytokine, thereby decreasing systemic glucose resistance and lipid storage. Meanwhile, rosiglitazone embedded within the adipose tissue promotes the browning of white adipocytes, and boosts energy expenditure, with further enhancement from luteolin, as demonstrated by decreased white adipose tissue masses. This localized intervention not only ensures the efficacy of combating obesity systemically but enhances overall metabolism while minimizing side effects.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113585"},"PeriodicalIF":10.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526178","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}

引用次数: 0

Nanomedicines as disruptors or inhibitors of biofilms: Opportunities in addressing antimicrobial resistance

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-03-01 DOI: 10.1016/j.jconrel.2025.113589

Jiaming Lan , Jingyu Zou , He Xin , Jin Sun , Tao Han , Mengchi Sun , Meng Niu

{"title":"Nanomedicines as disruptors or inhibitors of biofilms: Opportunities in addressing antimicrobial resistance","authors":"Jiaming Lan , Jingyu Zou , He Xin , Jin Sun , Tao Han , Mengchi Sun , Meng Niu","doi":"10.1016/j.jconrel.2025.113589","DOIUrl":"10.1016/j.jconrel.2025.113589","url":null,"abstract":"<div><div>The problem of antimicrobial resistance (AMR) has caused global concern due to its great threat to human health. Evidences are emerging for a critical role of biofilms, one of the natural protective mechanisms developed by bacteria during growth, in resisting commonly used clinical antibiotics. Advances in nanomedicines with tunable physicochemical properties and unique anti-biofilm mechanisms provide opportunities for solving AMR risks more effectively. In this review, we summarize the five “A” stages (adhesion, amplification, alienation, aging and allocation) of biofilm formation and mechanisms through which they protect the internal bacteria. Aimed at the characteristics of biofilms, we emphasize the design “THAT” principles (targeting, hacking, adhering and transport) of nanomedicines in their interactions with biofilms and internal bacteria. Furthermore, recent progresses in multimodal antibacterial nanomedicines, including biofilms disruption and bactericidal activity, and the types of currently available antibiofilm nanomedicines contained organic and inorganic nanomedicines are outlined and highlighted their potential applications in the development of preclinical research. Last but not least, we offer a perspective for the effectiveness of nanomedicines designed to address AMR and challenges associated with their clinical translation.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113589"},"PeriodicalIF":10.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Copper silicate nanoparticle-mediated delivery of astragaloside-IV for osteoarthritis treatment by remodeling the articular cartilage microenvironment

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-03-01 DOI: 10.1016/j.jconrel.2025.113583

Jianfeng Yang , Hongyi Jiang , Congcong Wu , Yuzhe Lin , Guancan Tan , Juannan Zhan , Lijiang Han , Yiting Zhu , Ping Shang , Liangle Liu , Haixiao Liu

{"title":"Copper silicate nanoparticle-mediated delivery of astragaloside-IV for osteoarthritis treatment by remodeling the articular cartilage microenvironment","authors":"Jianfeng Yang , Hongyi Jiang , Congcong Wu , Yuzhe Lin , Guancan Tan , Juannan Zhan , Lijiang Han , Yiting Zhu , Ping Shang , Liangle Liu , Haixiao Liu","doi":"10.1016/j.jconrel.2025.113583","DOIUrl":"10.1016/j.jconrel.2025.113583","url":null,"abstract":"<div><div>With the increasing global aging population, osteoarthritis (OA) has emerged as a major public health concern. OA pathogenesis is characterized by a complex interplay among inflammatory cytokines, reactive oxygen species, and extracellular matrix components, leading to cartilage degradation. Astragaloside-IV (AS-IV), a natural antioxidant, has shown promise in alleviating OA symptoms but is limited by poor bioavailability and ineffective cartilage drug delivery. To address these challenges, we aimed to develop a drug delivery system using copper silicate nanoparticles modified with polyethylene glycol and loaded with AS-IV (referred to as CSP@AS-IV). This system uses mesoporous silica nanoparticles with a hybrid metal framework to enhance drug release and efficacy. CSP@AS-IV degrades in the acidic OA microenvironment, releasing copper ions (Cu<sup>2+</sup>) and AS-IV, which synergistically exert antioxidant, antibacterial, anti-inflammatory, and chondroprotective effects. Both <em>in vitro</em> and <em>in vivo</em> rat model experiments demonstrated that CSP@AS-IV significantly alleviated joint inflammation, downregulated inflammatory marker expression, and promoted cartilage repair. These findings underscore that CSP@AS-IV offers considerable clinical potential for enhancing OA treatment outcomes.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113583"},"PeriodicalIF":10.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526088","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}

引用次数: 0

MicroRNA-induced reprogramming of tumor-associated macrophages for modulation of tumor immune microenvironment

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-28 DOI: 10.1016/j.jconrel.2025.113593

Yina Wu , Jinwon Park , Enzhen Xu , Dongyoon Kim , Jaiwoo Lee , Yu-Kyoung Oh

{"title":"MicroRNA-induced reprogramming of tumor-associated macrophages for modulation of tumor immune microenvironment","authors":"Yina Wu , Jinwon Park , Enzhen Xu , Dongyoon Kim , Jaiwoo Lee , Yu-Kyoung Oh","doi":"10.1016/j.jconrel.2025.113593","DOIUrl":"10.1016/j.jconrel.2025.113593","url":null,"abstract":"<div><div>Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment and typically exhibit pro-tumoral phenotypes. TAMs overexpress the signal regulatory protein alpha (SIRPα) receptor on their surface, which interacts with CD47 on tumor cells to inhibit their phagocytic activity. In this study, we developed lipid nanoparticles modified with an anti-SIRPα antibody (aSIRPα) for the targeted delivery of microRNA-155 (miR155@aSIRPα-LNP) to TAMs, aiming to enhance their anti-tumoral phenotypes within the tumor microenvironment. The aSIRPα modification not only facilitated nanoparticle uptake by TAMs rather than B16F10 cells, but also blocked the anti-phagocytosis signal by disrupting the interaction between SIRPα and CD47 on cancer cells. This dual functionality enhanced the expression of anti-tumoral phenotype markers in TAMs and activated macrophage-mediated phagocytosis of tumor cells. In a melanoma model, intratumoral administration of miR155@aSIRPα-LNP to B16F10 tumor-bearing mice reprogrammed TAMs toward anti-tumoral phenotypes. The anti-tumoral cytokines released by these TAMs remodeled the immunosuppressive tumor microenvironment, increasing cytotoxic T cell infiltration and reducing the regulatory T cell population, inhibiting tumor progression. This approach indicates the potential of miRNA-based therapies to overcome the limitations of current immunotherapies in treating cold solid tumors. Overall, the results suggest that delivering miR155 to TAMs by targeting SIRPα is a promising strategy for modulating the immunosuppressive tumor microenvironment in cancer immunotherapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113593"},"PeriodicalIF":10.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526090","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}

引用次数: 0

Conditional sequential delivery of ginkgetin and rapamycin orchestrates inflammation and autophagy to alleviate intervertebral disc degeneration

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-28 DOI: 10.1016/j.jconrel.2025.02.052

Jiaoxiang Chen , Xin Gan , Shenkai Su , Sizhe Jiao , Zailing Gong , Ziqiang Liu , Xiaopei Wu , Jun Jiang , Jiaming Zhang , Junlai Wan

{"title":"Conditional sequential delivery of ginkgetin and rapamycin orchestrates inflammation and autophagy to alleviate intervertebral disc degeneration","authors":"Jiaoxiang Chen , Xin Gan , Shenkai Su , Sizhe Jiao , Zailing Gong , Ziqiang Liu , Xiaopei Wu , Jun Jiang , Jiaming Zhang , Junlai Wan","doi":"10.1016/j.jconrel.2025.02.052","DOIUrl":"10.1016/j.jconrel.2025.02.052","url":null,"abstract":"<div><div>Intervertebral disc degeneration (IVDD) is a multifaceted and complex condition primarily driven by excessive inflammation, degradation of the extracellular matrix (ECM), and dysfunction of nucleus pulposus cells (NPCs). Despite extensive exploration of various therapeutic agents targeting IVDD, their efficacy remains disappointingly limited. This study underscores the efficacy of ginkgetin (GK), a natural bioflavonoid with potent anti-inflammatory properties, in mitigating inflammation as well as ECM degradation and NPC dysfunction triggered by interleukin-1β (IL-1β). However, GK alone cannot fully address the persistent obstruction in autophagic flux induced by IL-1β. To overcome this limitation, an innovative MMP13-responsive nanoplatform was developed, orchestrating the sequential delivery of GK and rapamycin (RA), targeting distinct phases of IVDD progression. In this design, GK is progressively released from exosomes during the initial phase, while RA is released from mesoporous silica nanoparticles during the mid-phase to enhance autophagic flux. This staged release approach leverages the strengths of both agents, addressing inflammation and restoring autophagy more effectively. In vivo experiments confirmed the substantial therapeutic benefits of this staggered delivery strategy in IVDD. The engineered MMP13-responsive nanoplatform represents a significant advancement in controlled, sequential drug delivery systems, offering a promising therapeutic avenue to effectively regulate inflammation and autophagy, thereby ameliorating IVDD.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113556"},"PeriodicalIF":10.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472530","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}

引用次数: 0

Harnessing sulfur-doped carbon nanodots conjugated with IDO inhibitors act as a dual-mode breast cancer immunotherapy 利用与 IDO 抑制剂共轭的掺硫纳米碳点作为双模式乳腺癌免疫疗法

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-28 DOI: 10.1016/j.jconrel.2025.02.071

Roberta Cillari , Rita C. Acúrcio , Andreia Barateiro , Helena F. Florindo , Nicolò Mauro , Gennara Cavallaro

{"title":"Harnessing sulfur-doped carbon nanodots conjugated with IDO inhibitors act as a dual-mode breast cancer immunotherapy","authors":"Roberta Cillari , Rita C. Acúrcio , Andreia Barateiro , Helena F. Florindo , Nicolò Mauro , Gennara Cavallaro","doi":"10.1016/j.jconrel.2025.02.071","DOIUrl":"10.1016/j.jconrel.2025.02.071","url":null,"abstract":"<div><div>Fluorescent ultrasmall nanoparticles (d < 10 nm), such as carbon nanodots (CDs), are promising nanosystems for precision cancer therapy. Their optimal size allows them to diffuse within complex microenvironments, enabling drug delivery, imaging, and monitoring. Additionally, CDs can be engineered to hold inherent nanotoxicity toward cancer cells, overcoming multidrug resistance associated with conventional drugs. Nevertheless, cancer is a multifactorial disease where combinational strategies are most likely to tackle metastatic tumors and efficiently avoid recidivism. Therefore, developing multifunctional CDs that exhibit intrinsic nanotoxicity against cancer cells and drive effective antitumor immune responses is a promising approach to improving patients' response rates.</div><div>Here, we developed an innovative nanosystem by conjugating N-,S-doped CDs with indoximod (IND) through a simple and cost-effective method. Our CDs-IND not only retained the advantages of bare CDs, including photoluminescence for self-tracking but also significantly controlled breast cancer progression <em>in vivo</em> following CDs-IND intratumoral (IT) and intravenous (IV) administration. Tumor microenvironment (TME) immune profiling revealed that CDs-IND reduced IDO expression and recruited NK, NKT, and T cells. This study underscores the potential of combining the inherent pharmacological properties of CDs with indoximod-mediated immunotherapy, offering a promising strategy for precision breast cancer treatment.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113575"},"PeriodicalIF":10.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517923","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}

引用次数: 0

Oxygen-regulated enzymatic nanoplatform for synchronous intervention in glycolysis and oxidative phosphorylation to augment antitumor therapy 用于同步干预糖酵解和氧化磷酸化以增强抗肿瘤疗法的氧调控酶纳米平台

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-28 DOI: 10.1016/j.jconrel.2025.113594

Shanshan Jiang , Wanyu Li , Yifan Zhang , Jing Lin , Peng Huang

{"title":"Oxygen-regulated enzymatic nanoplatform for synchronous intervention in glycolysis and oxidative phosphorylation to augment antitumor therapy","authors":"Shanshan Jiang , Wanyu Li , Yifan Zhang , Jing Lin , Peng Huang","doi":"10.1016/j.jconrel.2025.113594","DOIUrl":"10.1016/j.jconrel.2025.113594","url":null,"abstract":"<div><div>Tumor cells typically undergo metabolic reprogramming to obtain substantial energy <em>via</em> glycolysis and oxidative phosphorylation (OXPHOS). Intervening in this reprogramming is expected to have therapeutic effects, but simultaneous intervention in these two metabolic pathways is challenging. Herein, we developed an “open-source and throttling” oxygen (O₂) modulation strategy by which we can simultaneously intervene in these two metabolic pathways. Our O₂ modulation nanoplatform (denoted as OAGO) is fabricated <em>via</em> the self-assembly of glucose oxidase (GOx) and oligomycin A (OA) and is coated with bacterial outer membrane vesicles (OMVs). OAGO elicits simultaneous GOx-mediated inhibition of glycolysis and OA-induced inhibition of OXPHOS. The resulting production of GOx-catalyzed hydrogen peroxide leads to oxidative stress, which exacerbates the inhibition of mitochondrial function. Meanwhile, OA reduces intratumoral O₂ consumption (<em>i.e.</em>, the “throttling” strategy), and OMVs increase the tumor blood O₂ level (<em>i.e.</em>, the “open-source” strategy). This results in an increase in O₂ levels for GOx catalysis, thereby exacerbating energy consumption. In addition, OMVs increase intratumoral OAGO accumulation and enable photothermal therapy in the 4T1 mouse model, which also raises the tumor blood O₂ level and benefits GOx catalysis. This synchronous intervention in two metabolic pathways alongside O₂ modulation constitutes a promising approach for efficient antitumor therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113594"},"PeriodicalIF":10.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517920","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}

引用次数: 0