Journal of Controlled Release最新文献_第3页

Synergistic chemo-photothermal treatment via MXene-encapsulated nanoparticles for targeted melanoma therapy 通过 MXene 封装纳米粒子进行协同化疗-光热治疗，实现黑色素瘤靶向治疗

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-04-14 DOI: 10.1016/j.jconrel.2025.113729

Su Bin Lee , Jeong Min Park , Rowoon Park , Hye Eun Choi , Suck Won Hong , Ki Su Kim

{"title":"Synergistic chemo-photothermal treatment via MXene-encapsulated nanoparticles for targeted melanoma therapy","authors":"Su Bin Lee , Jeong Min Park , Rowoon Park , Hye Eun Choi , Suck Won Hong , Ki Su Kim","doi":"10.1016/j.jconrel.2025.113729","DOIUrl":"10.1016/j.jconrel.2025.113729","url":null,"abstract":"<div><div>Owing to its high photothermal conversion efficiency, MXene has garnered strong interest in biomedical applications. MXene has demonstrated significant promise particularly in chemo-photothermal cancer therapy. However, MXene's inherent instability in aqueous environments poses challenges for advanced biological applications. Here, we address this limitation by encapsulating MXene nanoparticles (NPs) within an amphiphilic polymer matrix of hyaluronic acid and poly(lactide-<em>co</em>-glycolide) (HA-PLGA/MX NPs), enhancing photothermal stability and functionality in physiological conditions. Moreover, to achieve targeted chemo-photothermal therapy, we co-loaded the anticancer agent paclitaxel (PTX) with HA-PLGA/MX (HA-PLGA/MXP NPs), facilitating simultaneous delivery of heat and drug to tumor sites. The HA-PLGA/MXP NPs were synthesized using a straightforward water-oil-water emulsion method and extensively characterized for drug release assays to confirm their suitability as dual-functional nanocarriers. Both in vitro and in vivo studies demonstrated that HA-PLGA/MXP NPs, under laser irradiation, achieved obviously enhanced therapeutic efficacy, with an ∼81.9 % cell death rate and a ∼95.7 % tumor inhibition rate, outperforming the effects of chemotherapy or photothermal therapy alone. Integrating MXene in HA-PLGA encapsulation introduces a potent platform for melanoma treatment, offering synergistic therapeutic potential by combining photothermal activity with sustained drug release, highlighting a promising approach to targeted cancer therapy, and advancing the field of NP-based chemo-photothermal therapeutics.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113729"},"PeriodicalIF":10.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831640","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

Promoting mitocytosis via gene-engineered aligned fibers for fascia regeneration

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-04-13 DOI: 10.1016/j.jconrel.2025.113725

Yiru Xu, Qimanguli Saiding, Xue Zhou, Rui Wang, Juan Wang, Wenguo Cui, Xinliang Chen

{"title":"Promoting mitocytosis via gene-engineered aligned fibers for fascia regeneration","authors":"Yiru Xu, Qimanguli Saiding, Xue Zhou, Rui Wang, Juan Wang, Wenguo Cui, Xinliang Chen","doi":"10.1016/j.jconrel.2025.113725","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113725","url":null,"abstract":"The abnormal accumulation of damaged mitochondria severely impedes tissue repair, and conventional therapeutic approaches, such as drug treatments, are often ineffective to remove damaged mitochondria. In this study, we developed gene-engineered aligned electrospun fibers by integrating microfluidic chip technology with a micro-sol oriented electrospinning technique. This study is the first to demonstrate the repair of damaged fascia by promoting mitocytosis through upregulating tetraspanin-9 (TSPAN9). The key gene for mitochondrial exocytosis, TSPAN9, was initially encapsulated into liposomes using microfluidic chip technology. Subsequently, core-shell structured aligned electrospun fibers were fabricated <em>via</em> oriented micro-sol electrospinning, where TSPAN9-loaded liposomes were protected by hyaluronic acid (HA) in the core layer, while aligned polylactic acid (PLA) fibers formed the outer shell layer. <em>In vitro</em> studies revealed that the aligned fibers closely mimicked the oriented structure of fascia tissue and significantly enhanced cell migration by providing directional physical cues. By sustained release of gene-loaded liposomes into cells, mitochondrial homeostasis was effectively restored, mitochondrial respiration was recovered, reactive oxygen species levels were reduced, and mitochondrial membrane potential was maintained. <em>In vivo</em> studies confirmed that these gene-engineered fibers effectively suppressed inflammatory responses and promoted fascia regeneration by facilitating the removal of damaged mitochondria through mitocytosis. In conclusion, gene-engineered fibers developed in this study, which enhance mitocytosis, offer a novel and promising therapeutic strategy for fascia tissue repair.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"26 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827566","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

Dimethylamino-based synthetic lipidoid nanoparticles for selective mRNA delivery to splenic antigen-presenting cells

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-04-13 DOI: 10.1016/j.jconrel.2025.113737

Xue Liang , Chenchen Zhang , Qimeng Yin , Yuerong Bai , Jiahao Li , Min Qiu

{"title":"Dimethylamino-based synthetic lipidoid nanoparticles for selective mRNA delivery to splenic antigen-presenting cells","authors":"Xue Liang , Chenchen Zhang , Qimeng Yin , Yuerong Bai , Jiahao Li , Min Qiu","doi":"10.1016/j.jconrel.2025.113737","DOIUrl":"10.1016/j.jconrel.2025.113737","url":null,"abstract":"<div><div>Targeted systemic mRNA delivery to extrahepatic tissues remains a formidable challenge, especially in the absence of targeting ligands on lipid nanoparticles. In this study, we introduce a series of dimethylamino-based ionizable lipidoids (DMA-Lipidoids) engineered for selective mRNA delivery to the spleen. Using a combinatorial approach, we synthesized 48 chemically distinct lipidoids by pairing four DMA-containing amine heads with 12 newly designed hyperbranched tails. Remarkably, lipidoids with tails H228, H226x, H246x, and H446x demonstrated exceptional spleen-targeting efficiency. To refine the lipidoid design, we constructed and screened a secondary library of 36 lipidoids containing DMA analogues. Through this two-round screening process, we identified lipidoids with both high potency and spleen selectivity. The lead candidate, DMA4-H228, achieved precise delivery of ovalbumin mRNA to antigen-presenting cells (APCs), driving interferon-α (IFN α) production and APC activation. This robust immune response effectively inhibited tumor growth. Overall, these innovative DMA-lipidoids demonstrate strong spleen-targeting capabilities, offering a transformative platform for mRNA vaccine development.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113737"},"PeriodicalIF":10.5,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827562","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

Intracellular processing of DNA-lipid nanoparticles: A quantitative assessment by image segmentation

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-04-12 DOI: 10.1016/j.jconrel.2025.113709

Alessandra Cavegn, Samuel Waldner, David Wang, Jaroslaw Sedzicki, Evrim Ümit Kuzucu, Michael Zogg, Claudia Lotter, Jörg Huwyler

{"title":"Intracellular processing of DNA-lipid nanoparticles: A quantitative assessment by image segmentation","authors":"Alessandra Cavegn, Samuel Waldner, David Wang, Jaroslaw Sedzicki, Evrim Ümit Kuzucu, Michael Zogg, Claudia Lotter, Jörg Huwyler","doi":"10.1016/j.jconrel.2025.113709","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113709","url":null,"abstract":"Carriers for efficient delivery of nucleic acids, such as lipid nanoparticles (LNPs), have gained much attention for gene therapy applications. Intracellular processing of such nanocarriers is a complex mechanism comprising cellular internalization by endocytosis pathways, endosomal release into the cytosol, lysosomal degradation, and recycling. The endosomal escape rates of current formulations are considered low, and methods to reliably quantify endocytic events are not readily available. To address this shortcoming and to support the optimization of LNP formulations, the current study presents an automated live-cell imaging-based analysis method. Engineered HuH7 hepatic cell lines overexpressing fluorescent Galectin and Rab reporters together with lysosomal co-staining enabled qualitative and quantitative tracking of DNA-loaded LNPs. The use of two fluorescently labeled DNA-LNP formulations containing either SM-102 or ALC-0315 ionizable lipids revealed significant differences in endosomal escape rates and intracellular processing. Upon treatment, only subpopulations of the HuH7 target cells could be activated with respect to escape or recycling. Recycling inhibitors were therefore used to promote endosomal escape. These findings provide valuable insights into the timing and regulation of endocytic events, which will be instrumental to optimize therapeutic LNP formulations.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"202 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822665","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

The therapeutic potential of mRNA-encoded SFTSV human monoclonal antibody encapsulated lipid nanoparticle in vivo

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-04-12 DOI: 10.1016/j.jconrel.2025.113735

Soo-Yeon Lee , Yebeen Lee , Eun Young Oh , Jisun Lee , Jae-Yong Kim , Sang-In Park , Hyo-Jung Park , So Hyun Park , Eun-Jin Choi , Dahyeon Ha , Ayoung Oh , Ayeon Kim , Hyo-Jin Ro , Yoo-Jin Bang , Hye Won Kwak , Hyeong-Jun Park , Do-Hyung Kim , Daegeun Kim , Sang-Myeong Lee , Nam-Hyuk Cho , Jae-Hwan Nam

{"title":"The therapeutic potential of mRNA-encoded SFTSV human monoclonal antibody encapsulated lipid nanoparticle in vivo","authors":"Soo-Yeon Lee , Yebeen Lee , Eun Young Oh , Jisun Lee , Jae-Yong Kim , Sang-In Park , Hyo-Jung Park , So Hyun Park , Eun-Jin Choi , Dahyeon Ha , Ayoung Oh , Ayeon Kim , Hyo-Jin Ro , Yoo-Jin Bang , Hye Won Kwak , Hyeong-Jun Park , Do-Hyung Kim , Daegeun Kim , Sang-Myeong Lee , Nam-Hyuk Cho , Jae-Hwan Nam","doi":"10.1016/j.jconrel.2025.113735","DOIUrl":"10.1016/j.jconrel.2025.113735","url":null,"abstract":"<div><div>Severe fever with thrombocytopenia syndrome (SFTS), caused by the SFTS virus (SFTSV), has emerged as a significant public health concern in East Asia since 2009. The high mortality rate of SFTS underscores the urgent need for effective preventive and therapeutic interventions. Although a Gn-specific human monoclonal antibody, Ab10, herein referred to as the protein S/A-TEN, has been previously reported, its development has been hindered by the economic challenges and low yields of large-scale production. To address this limitation, we developed an mRNA encapsulated lipid nanoparticle to produce SFTSV-specific human mAbs (mRNA S/A-TEN). This novel approach facilitates small-scale production, potentially enabling direct human application. The mRNA S/A-TEN antibody obtained from the injected-mouse serum showed high neutralizing antibody titers. Furthermore, we found that injecting the mRNA S/A-TEN antibody into mice that were infected with lethal SFTSV resulted in 100 % survival and assisted in a rapid recovery from organ failure. This study provides the first evidence that an mRNA-encoded SFTSV-specific human mAb can provide effective therapeutic protection against SFTSV infection, offering a promising therapeutic approach for the treatment of human SFTS.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113735"},"PeriodicalIF":10.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824800","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

Regulated cell death mechanisms in mitochondria-targeted phototherapy

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-04-12 DOI: 10.1016/j.jconrel.2025.113720

Qihang Ding , Hyeonji Rha , Changyu Yoon , Yujin Kim , So Jin Hong , Hui Ju Kim , Yang Li , Min Hee Lee , Jong Seung Kim

{"title":"Regulated cell death mechanisms in mitochondria-targeted phototherapy","authors":"Qihang Ding , Hyeonji Rha , Changyu Yoon , Yujin Kim , So Jin Hong , Hui Ju Kim , Yang Li , Min Hee Lee , Jong Seung Kim","doi":"10.1016/j.jconrel.2025.113720","DOIUrl":"10.1016/j.jconrel.2025.113720","url":null,"abstract":"<div><div>Phototherapy, comprising photodynamic therapy (PDT) and photothermal therapy (PTT), was first introduced over a century ago and has since evolved into a versatile cancer treatment modality. While numerous studies have explored regulated cell death (RCD) mechanisms induced by phototherapy, a comprehensive synthesis centered on mitochondria-targeted phototherapeutic strategies and agents as mediators of RCD is still lacking. This review provides a systematic and in-depth analysis of recent advances in mitochondria-centered mechanisms driving phototherapy-induced death pathways, including apoptosis, autophagy, pyroptosis, immunogenic cell death, ferroptosis, and cuproptosis. We highlight the critical role of mitochondria as central regulators of these death pathways in response to phototherapeutic interventions. Moreover, we discuss fundamental design strategies for developing precision-targeted phototherapeutic materials to enhance efficacy and minimize off-target effects. Finally, we identify prevailing challenges and propose future research directions to address these hurdles, paving the way for next-generation mitochondria-targeted phototherapy as a highly effective strategy for cancer management.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113720"},"PeriodicalIF":10.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822594","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

FS536, a novel nitric oxide-releasing doxorubicin hybrid, reverts multidrug resistance in lung cancer cells

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-04-12 DOI: 10.1016/j.jconrel.2025.113732

Benedetta Romano, Maria Cristina Molaro, Fabio Somma, Chiara Battisegola, Mariacristina Failla, Loretta Lazzarato, Konstantin Chegaev, Barbara Rolando, Joanna Kopecka, Angela Ianaro, Maria Grazia Rimoli, Carminia Maria Della Corte, Chiara Riganti, Federica Sodano, Giuseppe Ercolano

{"title":"FS536, a novel nitric oxide-releasing doxorubicin hybrid, reverts multidrug resistance in lung cancer cells","authors":"Benedetta Romano, Maria Cristina Molaro, Fabio Somma, Chiara Battisegola, Mariacristina Failla, Loretta Lazzarato, Konstantin Chegaev, Barbara Rolando, Joanna Kopecka, Angela Ianaro, Maria Grazia Rimoli, Carminia Maria Della Corte, Chiara Riganti, Federica Sodano, Giuseppe Ercolano","doi":"10.1016/j.jconrel.2025.113732","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113732","url":null,"abstract":"The design of molecular hybrids that chemically conjugate nitric oxide (NO)-donors with anticancer drugs, offering site-specific and time-controlled properties, is a promising strategy in cancer therapy. In this work, we designed, synthesized, and characterized a novel doxorubicin (<strong>DOXO</strong>)-NO-donor hybrid, named <strong>FS536</strong>, by chemically conjugating <strong>DOXO</strong> with a diazeniumdiolate moiety. Upon incubation in human serum, <strong>FS536</strong> simultaneously released both <strong>DOXO</strong> and NO through enzymatic hydrolysis. <strong>FS536</strong> significantly inhibited the proliferation of the <strong>DOXO</strong>-resistant A549 lung cancer cell line (A549-DR), overcoming the resistance typically observed with <strong>DOXO</strong> alone. This enhanced efficacy is attributed to the release of NO, which induces the nitration of the MRP1 efflux pump, reducing its activity, increasing intracellular drug concentrations, and thus sensitizing resistant cells to <strong>DOXO</strong>. Our findings suggest that <strong>FS536</strong> is a promising therapeutic strategy for combating multidrug-resistant cancers by leveraging the synergistic effects of <strong>DOXO</strong> and NO.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"27 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822597","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

Cancer nanomedicine from a clinician-scientist perspective: Lessons and prospects

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-04-12 DOI: 10.1016/j.jconrel.2025.113731

Alberto A. Gabizon

引用次数: 0

Tailoring the release of highly loaded amorphous solid dispersions via additive manufacturing

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-04-12 DOI: 10.1016/j.jconrel.2025.113723

Carolina Alva , Elisa Goetzinger , Josip Matić , Aygün Doğan , Eyke Slama , Sarah Heupl , Thomas Rillmann , Susanna Abrahmsén-Alami , Jonathan Booth , Sharareh Salar-Behzadi , Martin Spoerk

{"title":"Tailoring the release of highly loaded amorphous solid dispersions via additive manufacturing","authors":"Carolina Alva , Elisa Goetzinger , Josip Matić , Aygün Doğan , Eyke Slama , Sarah Heupl , Thomas Rillmann , Susanna Abrahmsén-Alami , Jonathan Booth , Sharareh Salar-Behzadi , Martin Spoerk","doi":"10.1016/j.jconrel.2025.113723","DOIUrl":"10.1016/j.jconrel.2025.113723","url":null,"abstract":"<div><div>In the last decades, tremendous improvements have been made in enhancing the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Lately, their customisation potential has become a reality through filament-based 3D-printing (3DP). Highly loaded oral amorphous solid dispersions (ASDs) are of particular interest, since they drastically reduce the pill burden. However, such systems are limited by their high tendency of API recrystallisation, compromising the API solubility and the mechanical properties of filaments fabricated for 3DP. The following work closes this gap by developing compact 3DP tablets containing an ASD system of 70 % itraconazole in hydroxypropyl methylcellulose acetate succinate (HPMCAS). The processability via HME and 3DP processes was thoroughly investigated by considering filament properties such as solid-state, rheology and mechanical behaviour. Even after six months of storage, the ASD did not show recrystallisation and maintained a zero-order drug release for variable 3DP infill patterns, demonstrating the potential of this approach for on-demand processing at the point-of-care. A strong differentiation in release kinetics was found for different infills that can be used for further improvement of the product to allow tailored release rates. This work provides a strong basis for successful personalisation of highly loaded ASDs via 3DP.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113723"},"PeriodicalIF":10.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822599","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

Oxidized fucoidan-based nanocomposite hydrogel for cryptotanshinone delivery and prevention of postoperative abdominal adhesions

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-04-12 DOI: 10.1016/j.jconrel.2025.113733

Tao Zhang , Xianmin Shi , Yanjuan Huang, Yujun Gong, Yuanfeng He, Danni Xiao, Shengzhi Wang, Chunshun Zhao

{"title":"Oxidized fucoidan-based nanocomposite hydrogel for cryptotanshinone delivery and prevention of postoperative abdominal adhesions","authors":"Tao Zhang , Xianmin Shi , Yanjuan Huang, Yujun Gong, Yuanfeng He, Danni Xiao, Shengzhi Wang, Chunshun Zhao","doi":"10.1016/j.jconrel.2025.113733","DOIUrl":"10.1016/j.jconrel.2025.113733","url":null,"abstract":"<div><div>Postoperative abdominal adhesions (PAA) are common diseases following abdominal surgery and can cause various serious complications. The excessive inflammation and oxidative stress are the main causes of PAA formation. Herein, we developed a nanomicellar hydrogel, OFu/HF@CTS, composed of oxidized fucoidan (OFu) and cryptotanshinone (CTS)-loaded hydrazine-functionalized pluronic F127 nanomicelles (HF127@CTS) for the effective prevention of PAA. The hydrogels exhibited satisfactory viscoelasticity, rapid self-healing ability, and good tissue adhesion properties, and were able to slowly release CTS for one week, with a cumulative release rate of 80 % on the 7th day. Additionally, the hydrogels could effectively reduce fibroblast cells and protein adhesions due to the high negative charge of OFu and have good biocompatibility towards RAW 264.7 and L929 cells. Moreover, CTS released from OFu/HF@CTS could efficiently reduce oxidative stress in macrophages and promote M1 macrophages polarized to M2 phenotype to relieve inflammation. In vivo results showed that OFu/HF@CTS hydrogel had good biodegradability and biosafety, and could effectively reduce PAA formation in a rat cecum-abdominal wall abrasion model through the mechanism of alleviating oxidative stress and inflammation, regulating fibrinolysis, and inhibiting fibrosis. This work highlights the therapeutic potential of drug-loaded nanomicellar hydrogels as a preventive strategy for PAA in clinical applications.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113733"},"PeriodicalIF":10.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822595","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