{"title":"Clinical insight-driven micron-sized cholesterol oxidation platform for membrane lipid therapy of advanced ovarian cancer.","authors":"Weidong Fei, Yu Xin, Wenqiang Qian, Mingqi Liu, Caihong Zheng, Yunxi Liu, Danfei Chen, Ying Zhou, Shanshan Xu, Xiaodong Wu, Mengdan Zhao","doi":"10.1186/s12951-025-03701-7","DOIUrl":"10.1186/s12951-025-03701-7","url":null,"abstract":"<p><p>Due to the insidious onset of ovarian cancer, the majority of patients are diagnosed at advanced stages, often presenting with extensive pelvic and abdominal metastasis. A significant proportion of these patients exhibit primary or acquired drug resistance, limiting improvements in the five-year survival rate. In this study, an analysis of patient-derived samples demonstrated a strong correlation between cholesterol levels and ovarian cancer progression. Membrane lipid therapy, a strategy that targets the composition, structure, and function of the cell membrane, has demonstrated notable potential in tumor therapy. Subsequently, a novel cholesterol oxidation-mediated membrane lipid therapy employing PLGA microspheres co-loaded with miriplatin (MiR) and cholesterol oxidase (COD) was proposed for drug-resistant advanced ovarian cancer therapy. The microspheres had a particle size of approximately 2.58 μm, with encapsulation efficiencies of 82.98 ± 0.09% for MiR and 32.83 ± 4.30% for COD. In vitro experiments demonstrated that COD-induced cholesterol oxidation modulated the membrane rigidity and fluidity of SKOV3-TR cells, thereby compromising membrane structural integrity and attenuating tumor cell migration. Additionally, the reactive oxygen species generated during cholesterol oxidation disrupted mitochondrial membrane potential and adenosine triphosphate production. The resulting energy deficiency and compromised membrane integrity reduced the expression and function of drug resistance-associated proteins, thereby enhancing chemosensitivity. Moreover, the combined effects of reactive oxygen species and MiR drove resistant cells towards apoptosis. In vivo studies demonstrated that the large-particle PLGA formulation effectively resided in the peritoneal cavity, resulting in superior therapeutic outcomes against drug-resistant metastatic ovarian tumor, as evidenced by fewer peritoneal metastatic nodules and diaphragmatic colonization sites, more extensive tumor tissue destruction, and prolonged survival. More importantly, PLGA encapsulation significantly decreased the toxic side effects associated with continuous platinum-based chemotherapy. Overall, cholesterol oxidation-mediated membrane lipid therapy represented a promising approach for treating advanced ovarian cancer.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"614"},"PeriodicalIF":12.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuo Wang, Yunhui Lv, Xiaohu Wang, Zhenhao Zhang, Jiafei Li, Tam In Pan, M A Chi Yung, Fengqing Zhang, Haotian Zhang, Jian Meng, Hong Lian, Shuang Wen, Xiaodong Hao, Peihe Wang, Qi Zhang, Ting He, Yongbao Zhang, Xianqiang Wang, Jiangping Song, Yongchun Cui
{"title":"MiR-7683-3p from M2-exosomes attenuated atherosclerosis by activating the PPARγ-LXRα-ABCG1 pathway mediated cholesterol efflux of vascular smooth muscle cell derived foam cells.","authors":"Shuo Wang, Yunhui Lv, Xiaohu Wang, Zhenhao Zhang, Jiafei Li, Tam In Pan, M A Chi Yung, Fengqing Zhang, Haotian Zhang, Jian Meng, Hong Lian, Shuang Wen, Xiaodong Hao, Peihe Wang, Qi Zhang, Ting He, Yongbao Zhang, Xianqiang Wang, Jiangping Song, Yongchun Cui","doi":"10.1186/s12951-025-03690-7","DOIUrl":"10.1186/s12951-025-03690-7","url":null,"abstract":"<p><strong>Background: </strong>Impaired excretion of lipid deposits within vascular smooth muscle cell-derived foam cells (VSMC-FCs) contributes to the ongoing expansion of the plaque necrotic core. This study aims to explore the effects and underlying mechanisms of exosomes secreted by M2 macrophage (M2-exos) on lipid metabolism of VSMC-FCs and plaque stability.</p><p><strong>Methods: </strong>First, immunofluorescence was used to detect the expression levels of CD45 (a recognized differentially-expressed molecule of myeloid and VSMC-FCs) and the key proteins of cholesterol efflux pathway, ABCA1 and ABCG1, in human early and late plaques. Next, an in vitro foam cell model was used to assess the effect and mechanism of M2-exos on lipid metabolism in vascular smooth muscle cells by western blot, Oil red O staining and cell total cholesterol assays. RNA-seq and quantitative real-time PCR were employed to characterize the miRNA profiles within M2-exos. The dual-luciferase reporting system and gene silencing approaches were utilized to assess the regulatory effect of candidate miRNA on target genes and signaling pathways. Subsequently, the effect of M2-exos on plaque progression and stability in ApoE<sup>-/-</sup> mice was evaluated using Oil Red O, H&E, Masson's trichrome, Movat's Pentachrome, and immunohistochemistry.</p><p><strong>Results: </strong>Immunofluorescence revealed that compared to early plaques, VSMC-FCs (CD45<sup>-</sup>) were significantly increased in late plaques, and the expression levels of ABCG1 and ABCA1 were remarkably reduced compared to those in leukocyte-derived foam cells (CD45<sup>+</sup>). Purified M2-exos treatment significantly promoted the cholesterol efflux of VSMC-FCs in vitro. In high-fat-fed ApoE<sup>-/-</sup> mice, M2-exos significantly reduced the VSMC-FCs, delayed plaque progression, decreased the necrotic core area, and enhanced plaque stability. MiRNA profiling and analysis of signaling pathways identified miR-7683-3p as a key component in M2-exos, which modulated lipid metabolism in SMC-FCs lipid metabolism through the PPARγ-LXRα-ABCG1 pathway. Dual-luciferase reporting assay confirmed that miR-7683-3p could specifically bind to the promoter region of homeobox genes A1(HOXA1), an inhibitory factor of the PPARγ-LXRα-ABCG1 pathway.</p><p><strong>Conclusion: </strong>M2-exos exerted an obvious atherosclerotic protective effect, and the underlying mechanism was closely related to MiR-7683-3p, which targeted the 3'UTR of HOXA1 mRNA and activated the PPARγ-LXRα-ABCG1 mediated cholesterol efflux in VSMC-FCs.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"618"},"PeriodicalIF":12.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aligned nanofiber-based responsive sponge scaffolds for peripheral nerve regeneration.","authors":"Sizhe Song, Ying Zhang, Dongyu Xu, Hui Zhang, Yu Wang, Huan Wang, Hao Wu, Renjie Chai","doi":"10.1186/s12951-025-03683-6","DOIUrl":"10.1186/s12951-025-03683-6","url":null,"abstract":"<p><p>Nerve conduits have demonstrated tremendous value in advancing nerve regeneration. The current research focuses on improving their neuro regenerative effects through structural optimization and functional enhancement. Here, an original responsive sponge nerve conduit (RSNC) comprising a three-dimensional (3D) foamed nanofiber scaffold integrated with polydopamine-coated black phosphorus (PDA@BP) hydrogel is developed to promote sciatic nerve regeneration. The aligned nanofibrous mats are prepared by electrospinning and then foamed by gas foaming technology to obtain 3D sponge nanofiber scaffolds, which are subsequently filled with conductive PDA@BP doped gelatin methacryloyl hydrogels. Leveraging the superior photothermal conversion efficiency of PDA@BP nanosheets, loaded nerve growth factors are released under near-infrared light exposure, thereby promoting cell differentiation. In vivo experiments notably prove that RSNCs excel in facilitating nerve regeneration and motor function recovery, highlighting their potential for clinical peripheral nerve repair and related biomedical applications.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"617"},"PeriodicalIF":12.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junfeng Ke, Yuxin Tian, Tongjia Zhang, Anran Li, You Zhou, Yifan Cao, Liping Wang
{"title":"Enhanced multienzyme catalytic activity of Mn MOF induced by bioligands for efficient tumor therapy.","authors":"Junfeng Ke, Yuxin Tian, Tongjia Zhang, Anran Li, You Zhou, Yifan Cao, Liping Wang","doi":"10.1186/s12951-025-03694-3","DOIUrl":"10.1186/s12951-025-03694-3","url":null,"abstract":"<p><p>Nanozymes, as substitutes for natural enzymes, are widely used in various fields, such as cancer treatment. However, most nanozymes have low catalytic activity and selectivity, greatly limiting their clinical applications. Here, we propose a new design concept for nanozymes: modifying nanozymes with suitable multifunctional bioligands. This approach not only endows multiple biological functions but also enhances the multienzyme activity of nanozymes and avoids the effect of surface modification on nanozyme activity. In brief, this paper uses multifunctional bioligands to modify Mn MOF to obtain the nanozyme HPMZIF, which exhibits excellent biocompatibility and tumor-targeting ability. Interestingly, polyethyleneimine (PEI) modification not only effectively enhances the biocompatibility of Mn MOF, but also increases the peroxidase (POD)-, oxidase (OXD)- and glutathione peroxidase (GPx)-like activities of Mn MOF nanozymes. Furthermore, hyaluronic acid (HA) modification imparts the Mn MOF nanozymes with tumor targeting ability and enhanced the OXD- and GPx-like activities of the Mn MOF nanozymes. Ultimately, our nanoplatform cascade enhanced pyroptosis, chemotherapy, and chemodynamic therapy (CDT), significantly inhibiting the growth of 4T1 xenograft tumors. In summary, this work provides a feasible strategy for designing nanozymes with high activity and diverse biological functions, and offers new perspectives on the clinical translation of nanozymes.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"608"},"PeriodicalIF":12.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neutrophil membrane-camouflaged SiRNA nanoplatform targeting IL-33 attenuates osteoarthritis through autophagy-dependent senescence regulation.","authors":"Zeze Fu, Jiahao Chen, Dengshuo Sun, Siqi Zhang, Jian Chen","doi":"10.1186/s12951-025-03686-3","DOIUrl":"10.1186/s12951-025-03686-3","url":null,"abstract":"<p><p>Osteoarthritis (OA) imposes a substantial health and economic burden globally. Currently, there is a lack of disease-modifying osteoarthritis drugs (DMOADs). This study aimed to elucidate the relationship between chondrocyte senescence and OA progression, as well as to develop an effective siRNA nanodelivery platform for OA treatment. We engineered neutrophil membrane-coated, siIL33-loaded nanoparticles (NM-NP-siIL33) for OA management. The therapeutic efficacy of NM-NP-siIL33 was evaluated through both in vitro and in vivo experiments. Our findings revealed that IL-33 expression was significantly upregulated in damaged articular cartilage in both young and aged mice following anterior cruciate ligament transection (ACLT) surgery. In vitro experiments demonstrated that IL-33 promotes chondrocyte senescence by inhibiting cellular autophagy via activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Additional in vivo studies showed that NM-NP-siIL33 effectively delivered siIL33 to target cells within OA tissues, thereby mitigating the degradation of articular cartilage. Our results suggest that IL-33 plays a critical role in OA progression by accelerating chondrocyte senescence. Furthermore, NM-NP-siIL33 represents a promising therapeutic strategy for managing OA.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"610"},"PeriodicalIF":12.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chunhong Du, Shuai Wang, Yijie Cheng, Jie Li, Yufei Zhang, Zhuohao Li, Baolin Zhu, Zhongming Wu, Xinge Zhang, Lingyi Zhou
{"title":"Neutrophil membrane-encapsulated nanosonosensitizer with ultrasound-reinforced ferroptosis in Pseudomonas aeruginosa pneumonia.","authors":"Chunhong Du, Shuai Wang, Yijie Cheng, Jie Li, Yufei Zhang, Zhuohao Li, Baolin Zhu, Zhongming Wu, Xinge Zhang, Lingyi Zhou","doi":"10.1186/s12951-025-03676-5","DOIUrl":"10.1186/s12951-025-03676-5","url":null,"abstract":"<p><p>Pneumonia caused by Pseudomonas aeruginosa (P. aeruginosa) infection remains a formidable clinical challenge due to persistent biofilm formation and intrinsic antibiotic resistance, exacerbated by bacterial iron homeostasis that stabilizes biofilm architecture and neutralizes oxidative stress. Herein, we present Fe/TNT@NM, a biomimetic nanosonosensitizer activated by ultrasound (US) to dismantle biofilms through dual extracellular-intracellular mechanisms. The nanosonosensitizer features an iron-doped titanate nanotube (Fe/TNT) core encapsulated within a neutrophil membrane (NM). Under US irradiation, Fe/TNT@NM generates sonodynamic reactive oxygen species (ROS) extracellularly and enhances Fe<sup>3+</sup> release. These ions catalyze the Fenton reaction extracellularly to amplify chemodynamic effects and disrupt intracellular iron homeostasis, triggering bacterial ferroptosis. The NM coating enables immune evasion and biofilm-targeted delivery. This ultrasound-reinforced ferroptosis strategy synchronizes extracellular ROS storms with intracellular iron dyshomeostasis, achieving dual-action biofilm dismantling and eradication of drug-resistant P. aeruginosa. In a murine pneumonia model, Fe/TNT@NM suppresses biofilms and mitigates pulmonary injury. By converging biomimetic targeting, sonodynamic-chemodynamic cascades, and ultrasound-augmented ferroptosis, this nanosonosensitizer presents a paradigm-shifting approach to combat refractory biofilm infections and antibiotic resistance.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"607"},"PeriodicalIF":12.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Injectable responsive hydrogel with synergistic antibacterial and anti-inflammatory properties for enhanced periodontitis treatment.","authors":"Xinjie Li, Zhidong Zhang, Xin Yang, Mengyu Yu, Yanjiao Tang, Jinxian Wei, Zhige Li, Jun Hai, Baoping Zhang","doi":"10.1186/s12951-025-03698-z","DOIUrl":"10.1186/s12951-025-03698-z","url":null,"abstract":"<p><p>Periodontitis is a chronic inflammatory disease driven by dysbiotic microbial biofilms and localized reactive oxygen species (ROS) accumulation, with inflammation management made challenging by recurrent infections from residual pathogenic bacteria in the periodontal pockets. To address this, we engineered an injectable pH-responsive hydrogel (MH@ZIF-8/CS/β-GP) through the integration of minocycline hydrochloride (MH)-encapsulated zeolitic imidazolate framework-8 (ZIF-8) nanoparticles into a chitosan (CS) and β-glycerophosphate (β-GP) crosslinked matrix. The MH@ZIF-8 displayed broad-spectrum antimicrobial efficacy against key periodontal pathogens including Porphyromonas gingivalis (Pg), and Aggregatibacter actinomycetemcomitans (Aa), primarily attributed to the synergistic antimicrobial effects of Zn ions and MH. Additionally, MH@ZIF-8 effectively eliminated ROS by inhibiting the NLRP3/Caspase-1/IL-1β signaling pathway, demonstrating potent anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The MH@ZIF-8/CS/β-GP hydrogel, which exhibited favored cytocompatibility with human gingival fibroblasts (HGFs), undergoed a rapid sol-gel transition and pH-responsive sustained-release drug delivery under the acidic conditions of periodontal pockets, effectively responding to periodontitis microenvironment. Meanwhile, this hydrogel effectively alleviated alveolar bone loss in vivo. Overall, the developed MH@ZIF-8/CS/β-GP hydrogel presents a novel strategy for chronic periodontitis treatment and demonstrates promising clinical application potential.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"611"},"PeriodicalIF":12.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deqiang Ruan, Chong Hu, Zeping Yang, Fan Zhang, Bin Guo, Yimin Lei, Daniel Jaque, Yingli Shen, Fu Wang
{"title":"Rapid in situ microwave-assisted fabrication of ultrabright near-infrared probe for low-dose in vivo inflammatory imaging.","authors":"Deqiang Ruan, Chong Hu, Zeping Yang, Fan Zhang, Bin Guo, Yimin Lei, Daniel Jaque, Yingli Shen, Fu Wang","doi":"10.1186/s12951-025-03692-5","DOIUrl":"10.1186/s12951-025-03692-5","url":null,"abstract":"<p><p>Fluorescent probes operating within the near-infrared second window (NIR-II, 1000-1700 nm), characterized by high tissue transparency and minimal tissue-induced photon scattering/absorption, have been widely applied for early-stage disease diagnosis. However, the capability of NIR-II emitters for deep-tissue imaging is limited by relatively low brightness, which hinders the acquisition of images at low excitation intensity and administration dose. Herein, we introduce a novel in situ strategy to fabricate ultrabright Ag<sub>2</sub>S nanoparticles (Ag<sub>2</sub>S super NPs) via aftertreatment of chemically synthesized Ag<sub>2</sub>S NPs, where a protective shell grown by a 2-minutes rapid microwave irradiation. This shell effectively reduces the surface and structural defects, resulting in a 25-fold promotion of the quantum yield and 38-times increment of the fluorescence lifetime. The nontoxic PEGylated Ag<sub>2</sub>S super NPs enable in vivo deep-tissue imaging under low excitation laser (1 mW/cm<sup>2</sup>) and administration dose (0.5 mg/kg). Furthermore, after the modification with targeting peptide, Ag<sub>2</sub>S super NPs exhibit outstanding imaging performance by achieving an over 90% intensity promotion compared to commercial Ag<sub>2</sub>S NPs for targeted inflammation imaging in gastritis and myocarditis models. These results present an effective, cost-effective and rapid enhancement approach to obtain ultrabright NIR-II imaging contrast agent, thereby advancing their potential for pre-clinical diagnosis imaging applications.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"606"},"PeriodicalIF":12.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biomimetic Cu<sub>2-x</sub>Se nanoplatforms for efficient glioblastoma treatment: overcoming the blood-brain barrier and boosting Immunogenetic cell death.","authors":"Sijia Lin, Haiyan Xing, Yu Zeng, Elvira Galimova, Alexandr Chernov, Guodong Liu, Peng Xue","doi":"10.1186/s12951-025-03696-1","DOIUrl":"10.1186/s12951-025-03696-1","url":null,"abstract":"<p><p>Glioblastoma (GBM) is an aggressive and highly heterogeneous brain tumor that continues to pose a significant clinical challenge. Current therapeutic strategies, including surgical resection, radiotherapy, and chemotherapy, are hindered by the tumor's invasive behavior, resistance to treatment, and the difficulty of selectively targeting tumor cells. Emerging modalities, such as immunotherapy and photodynamic therapy, hold considerable promise; however, their efficacy in treating GBM is limited by critical barriers, including poor penetration of the blood-brain barrier (BBB), tumor heterogeneity, and insufficient accumulation of therapeutic agents at the tumor site. In this study, innovative biomimetic copper selenide nanoparticles (CS@CM) are developed for targeted photothermal therapy of GBM. These nanoparticles are functionalized with glioma cell membranes (CM), and this biomimetic design leverages the homing capability of the membranes to achieve efficient BBB penetration and enhanced targeting of GBM tissues. CS@CM act as potent photothermal agents upon light activation, which can amplify reactive oxygen species-induced oxidative stress to damage glioma cells. Such combination therapy effectively triggers immunogenic cell death to achieve splendid antitumor efficacy, offering a promising therapeutic strategy for GBM. Collectively, this approach addresses the limitations of conventional treatments, paving the way for improved clinical outcomes in managing this formidable malignancy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"609"},"PeriodicalIF":12.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quadruple synergistic amplification of ferroptosis for precision glioblastoma therapy: a luteolin-coordinated ferric ion nanoplatform.","authors":"Suyi Liu, Kunhui Sun, Mengnan Li, Xinyue Liu, Ping Wang, Meifang Li, Bo Peng, Bing Wang, Yan-Xu Chang, Xie-An Yu","doi":"10.1186/s12951-025-03688-1","DOIUrl":"10.1186/s12951-025-03688-1","url":null,"abstract":"<p><p>Ferroptosis is emerging as a promising therapeutic strategy for glioblastoma (GBM). However, insufficient lipid peroxidation levels and blood-brain barrier (BBB) pose a significant challenge for GBM treatment. Here, we present natural product luteolin (Lut)-coordinated Fe<sup>3+</sup> nanoparticles loaded with dihydroartemisinin (DHA), designated as FLD NPs, which can cross the BBB and induce quadruple amplified ferroptosis. Specifically, FLD NPs leverage four mechanisms to enhance ferroptosis: (1) Lut upregulates heme oxygenase 1 (HO-1), promoting heme degradation and recruiting endogenous Fe<sup>2+</sup>. (2) exogenous Fe<sup>3+</sup> depletes glutathione (GSH), increasing Fe<sup>2+</sup> levels and catalyzing H<sub>2</sub>O<sub>2</sub> to generate ·OH via the Fenton reaction; (3) Fe<sup>2+</sup> facilitates the cleavage of DHA's peroxide bridge, further elevating ·OH production; and (4) Lut-coordinated Fe<sup>3+</sup> acts as a photothermal agent, accelerating the Fenton reaction under light irradiation. Furthermore, FLD NPs enable multimodal imaging capabilities, including photoacoustic and photothermal imaging, for precise tumor targeting. It demonstrates satisfactory antitumor efficacy in GBM models, highlighting its potential as a novel ferroptosis-amplifying nanotherapeutic. Importantly, this study reveals that Lut modulates tight junction protein expression in vascular endothelial cells, facilitating BBB penetration. This work highlights a novel strategy for GBM therapy, leveraging natural product-mediated nanoparticles to amplify ferroptosis.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"605"},"PeriodicalIF":12.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}