Pub Date : 2025-11-01Epub Date: 2025-10-24DOI: 10.1016/j.nano.2025.102871
Afzaal Nadeem Mohammad , Yesenia Moreno , Garrett Grischo , Ying Liang , Stephanie Iusim , Sally Suliman , Ting Wang , Vladimir V. Kalinichenko , Kenneth S. Knox , Mrinalini Kala
With widespread use of carbon nanotubes (CNTs) in manufacturing, the public is increasingly exposed to these materials being released into the environment, with concerns of potential adverse effects on respiratory health. Studies have demonstrated that exposure to CNTs initiates inflammatory cascades and oxidative stress. CNT inhalation challenge in rodents often produces granulomatous inflammation and lung fibrosis. CNT exposure causes TH2 asthmatic inflammation in animal models. CNTs are implicated in disrupting the delicate balance of extracellular matrix homeostasis, contributing to fibrotic remodeling. Limited mechanistic studies exist but epidemiological data suggest a link between CNT exposure and the development of fibrotic and granulomatous lung diseases. In this review, we will discuss the impact of CNT exposure on the respiratory system and how CNT can be used in modeling lung disease.
{"title":"Impact of carbon nanotubes on pulmonary disorders attributed to occupational and environmental exposures","authors":"Afzaal Nadeem Mohammad , Yesenia Moreno , Garrett Grischo , Ying Liang , Stephanie Iusim , Sally Suliman , Ting Wang , Vladimir V. Kalinichenko , Kenneth S. Knox , Mrinalini Kala","doi":"10.1016/j.nano.2025.102871","DOIUrl":"10.1016/j.nano.2025.102871","url":null,"abstract":"<div><div>With widespread use of carbon nanotubes (CNTs) in manufacturing, the public is increasingly exposed to these materials being released into the environment, with concerns of potential adverse effects on respiratory health. Studies have demonstrated that exposure to CNTs initiates inflammatory cascades and oxidative stress. CNT inhalation challenge in rodents often produces granulomatous inflammation and lung fibrosis. CNT exposure causes TH2 asthmatic inflammation in animal models. CNTs are implicated in disrupting the delicate balance of extracellular matrix homeostasis, contributing to fibrotic remodeling. Limited mechanistic studies exist but epidemiological data suggest a link between CNT exposure and the development of fibrotic and granulomatous lung diseases. In this review, we will discuss the impact of CNT exposure on the respiratory system and how CNT can be used in modeling lung disease.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"70 ","pages":"Article 102871"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-10-19DOI: 10.1016/j.nano.2025.102870
Henan Zhang , Yanbin Liu , Xuezhi Gao , Guoli Ji , Yanzhen Zheng , Fei Luo , Xing Qi , Shasha Zhao , Shanghui Guan , Cong Wang , Ming Lu
Triple-negative breast cancer (TNBC) frequently develops resistance to radiotherapy, while its metabolic reliance on glucose and glutamine presents new therapeutic targets for radiotherapy sensitization. This study developed a targeted nanoliposome (G/B-Lip-R) co-delivering glucose oxidase (GOD) and buthionine sulfoximine (BSO) to enhance radiotherapy through dual metabolic intervention. GOD catalyzes glucose oxidation to generate hydrogen peroxide (H2O2) while depleting tumor energy supplies, whereas BSO inhibits glutathione (GSH) synthesis to disrupt redox homeostasis. Their synergistic action significantly elevates intracellular reactive oxygen species (ROS) levels, thereby potentiating radiosensitivity. Both in vitro and in vivo studies demonstrated that G/B-Lip-R effectively targets tumors and significantly improves radiotherapy outcomes. This work innovatively combines nanocarriers with dual metabolic pathway modulation, offering a novel strategy to overcome TNBC radioresistance with important clinical translation potential.
三阴性乳腺癌（TNBC）经常对放疗产生耐药性，而其对葡萄糖和谷氨酰胺的代谢依赖为放疗增敏提供了新的治疗靶点。本研究开发了一种靶向纳米脂质体（G/ b - lipr）共同递送葡萄糖氧化酶（GOD）和丁硫氨酸亚砜胺（BSO），通过双代谢干预增强放疗。GOD催化葡萄糖氧化生成过氧化氢（H2O2），同时消耗肿瘤能量供应，而BSO抑制谷胱甘肽（GSH）合成，破坏氧化还原稳态。它们的协同作用显著提高细胞内活性氧（ROS）水平，从而增强放射敏感性。体外和体内研究均表明G/B-Lip-R能有效靶向肿瘤，显著改善放疗效果。本研究创新性地将纳米载体与双代谢途径调制相结合，为克服TNBC放射耐药提供了一种具有重要临床转化潜力的新策略。
{"title":"Dual metabolic targeting liposomes potentiate triple-negative breast cancer radiosensitivity via glucose and glutathione starvation","authors":"Henan Zhang , Yanbin Liu , Xuezhi Gao , Guoli Ji , Yanzhen Zheng , Fei Luo , Xing Qi , Shasha Zhao , Shanghui Guan , Cong Wang , Ming Lu","doi":"10.1016/j.nano.2025.102870","DOIUrl":"10.1016/j.nano.2025.102870","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) frequently develops resistance to radiotherapy, while its metabolic reliance on glucose and glutamine presents new therapeutic targets for radiotherapy sensitization. This study developed a targeted nanoliposome (G/B-Lip-R) co-delivering glucose oxidase (GOD) and buthionine sulfoximine (BSO) to enhance radiotherapy through dual metabolic intervention. GOD catalyzes glucose oxidation to generate hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) while depleting tumor energy supplies, whereas BSO inhibits glutathione (GSH) synthesis to disrupt redox homeostasis. Their synergistic action significantly elevates intracellular reactive oxygen species (ROS) levels, thereby potentiating radiosensitivity. Both <em>in vitro</em> and <em>in vivo</em> studies demonstrated that G/B-Lip-R effectively targets tumors and significantly improves radiotherapy outcomes. This work innovatively combines nanocarriers with dual metabolic pathway modulation, offering a novel strategy to overcome TNBC radioresistance with important clinical translation potential.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"70 ","pages":"Article 102870"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-09-19DOI: 10.1016/j.nano.2025.102858
Angela Sharma, Atul Dev, Subhasree Roy Choudhury, Surajit Karmakar
Neuroblastoma (NB) is a neuroendocrine tumor derived from neural crest progenitor cells, commonly arising along the sympathetic nervous system, especially in the adrenal medulla. Despite therapeutic advances, the prognosis for advanced-stage NB remains poor, necessitating improved treatment options. 4HPR has demonstrated cytotoxicity in various tumors, including NB, with low systemic toxicity; however, its clinical use is restricted by poor solubility and bioavailability. To address this, we developed a human serum albumin-based nanoformulation of 4HPR using a simple desolvation method. This formulation effectively induced apoptosis in NB cells, marked by increased ROS generation, elevated Bax/Bcl-2 ratio, and enhanced cell detachment. Notably, we identified for the first time that MAPKAPK3 downregulation leads to reduced Bax phosphorylation and increased mitochondrial translocation. Co-immunoprecipitation confirmed a direct MAPKAPK3–Bax interaction, indicating MAPKAPK3 regulates Bax via phosphorylation. Our nanoformulation modulates this cross-talk, demonstrating promising translational potential as a novel therapeutic strategy for neuroblastoma.
{"title":"4HPR nanoformulation regulates MAPKAPK3/3pK signaling to control Bax phosphorylation and mitochondrial translocation to execute apoptosis in neuroblastoma","authors":"Angela Sharma, Atul Dev, Subhasree Roy Choudhury, Surajit Karmakar","doi":"10.1016/j.nano.2025.102858","DOIUrl":"10.1016/j.nano.2025.102858","url":null,"abstract":"<div><div>Neuroblastoma (NB) is a neuroendocrine tumor derived from neural crest progenitor cells, commonly arising along the sympathetic nervous system, especially in the adrenal medulla. Despite therapeutic advances, the prognosis for advanced-stage NB remains poor, necessitating improved treatment options. 4HPR has demonstrated cytotoxicity in various tumors, including NB, with low systemic toxicity; however, its clinical use is restricted by poor solubility and bioavailability. To address this, we developed a human serum albumin-based nanoformulation of 4HPR using a simple desolvation method. This formulation effectively induced apoptosis in NB cells, marked by increased ROS generation, elevated Bax/Bcl-2 ratio, and enhanced cell detachment. Notably, we identified for the first time that MAPKAPK3 downregulation leads to reduced Bax phosphorylation and increased mitochondrial translocation. Co-immunoprecipitation confirmed a direct MAPKAPK3–Bax interaction, indicating MAPKAPK3 regulates Bax via phosphorylation. Our nanoformulation modulates this cross-talk, demonstrating promising translational potential as a novel therapeutic strategy for neuroblastoma.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"70 ","pages":"Article 102858"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-10-10DOI: 10.1016/j.nano.2025.102867
Jaqueline Cardoso Jacintho , Ana Clara Nogueira Ferreira , Thiago Lopes Rocha
Nanotechnology-based approaches (NBA) can improve tumor diagnosis and treatment. Thus, zebrafish (Danio rerio) emerge as a model system to investigate antitumoral effects, biodistribution and mechanism of action of nanomaterials (NMs). The current study aimed to summarize and critically analyze the literature concerning the use of zebrafish as an in vivo model for assessing the NBA in diagnosis, therapy and theranostics of cancer. Revised data (n = 95) showed an increasing number of publications in recent years. The main study approach was therapeutic (83.16 %), while diagnosis and theranostics represented 9.47 % and 7.37 %, respectively. 95.8 % used the embryo-larval stage of zebrafish. The most studied NM was the nanoparticles (NPs). Breast cancer, liver and melanoma were the tumors most studied. Overall, NMs can reduce chemotherapeutic drug toxicity, inhibit tumor growth, metastasis and angiogenesis, also promote tumor imaging and tracking. Zebrafish is a suitable emerging model system in cancer nanomedicine research.
{"title":"Zebrafish as a model for assessing the nanotechnology-based approaches in cancer diagnosis, therapy and theranostic: A historical review, trends and challenges","authors":"Jaqueline Cardoso Jacintho , Ana Clara Nogueira Ferreira , Thiago Lopes Rocha","doi":"10.1016/j.nano.2025.102867","DOIUrl":"10.1016/j.nano.2025.102867","url":null,"abstract":"<div><div>Nanotechnology-based approaches (NBA) can improve tumor diagnosis and treatment. Thus, zebrafish (<em>Danio rerio</em>) emerge as a model system to investigate antitumoral effects, biodistribution and mechanism of action of nanomaterials (NMs). The current study aimed to summarize and critically analyze the literature concerning the use of zebrafish as an <em>in vivo</em> model for assessing the NBA in diagnosis, therapy and theranostics of cancer. Revised data (n = 95) showed an increasing number of publications in recent years. The main study approach was therapeutic (83.16 %), while diagnosis and theranostics represented 9.47 % and 7.37 %, respectively. 95.8 % used the embryo-larval stage of zebrafish. The most studied NM was the nanoparticles (NPs). Breast cancer, liver and melanoma were the tumors most studied. Overall, NMs can reduce chemotherapeutic drug toxicity, inhibit tumor growth, metastasis and angiogenesis, also promote tumor imaging and tracking. Zebrafish is a suitable emerging model system in cancer nanomedicine research.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"70 ","pages":"Article 102867"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-10-02DOI: 10.1016/j.nano.2025.102865
Qinghui Cao , Yihui Ge , Tong Wang, Ke Lin, Sidong Xiong, Yan Yue
Coxsackievirus B3 (CVB3) is a common cause of viral myocarditis, necessitating the development of prophylactic vaccines.. AD-Exo, a dual-targeting exosome vaccine, was developed to induce immune responses via targeting draining lymph nodes (dLNs) and dendritic cells (DCs). By incorporating an albumin-binding domain (ABD) peptide and a DC-guiding peptide (DCpep) into our previous CVB3 exosome vaccine (Exo), the AD-Exo vaccine demonstrated superior immunogenicity. It efficiently bound to mouse serum albumin, amplified antigen enrichment in dLNs, and enhanced DC uptake and maturation. Subcutaneous immunization in mice elicited significantly higher CVB3-specific serum neutralizing IgG with greater affinity than Exo and single-targeting vaccines. It induced robust T cell proliferation and CTL responses, increasing IFN-γ-producing CD4+ and CD8+ T cells. Ultimately, the AD-Exo vaccine reduced cardiac viral load, minimized histopathological damage, and significantly improved survival in challenged mice. This strategy provided novel perspectives for the development of dual-targeting prophylactic vaccines against viral myocarditis.
{"title":"Dual-targeting exosome vaccine confers efficient protection against CVB3-induced myocarditis","authors":"Qinghui Cao , Yihui Ge , Tong Wang, Ke Lin, Sidong Xiong, Yan Yue","doi":"10.1016/j.nano.2025.102865","DOIUrl":"10.1016/j.nano.2025.102865","url":null,"abstract":"<div><div>Coxsackievirus B3 (CVB3) is a common cause of viral myocarditis, necessitating the development of prophylactic vaccines.. AD-Exo, a dual-targeting exosome vaccine, was developed to induce immune responses via targeting draining lymph nodes (dLNs) and dendritic cells (DCs). By incorporating an albumin-binding domain (ABD) peptide and a DC-guiding peptide (DCpep) into our previous CVB3 exosome vaccine (Exo), the AD-Exo vaccine demonstrated superior immunogenicity. It efficiently bound to mouse serum albumin, amplified antigen enrichment in dLNs, and enhanced DC uptake and maturation. Subcutaneous immunization in mice elicited significantly higher CVB3-specific serum neutralizing IgG with greater affinity than Exo and single-targeting vaccines. It induced robust T cell proliferation and CTL responses, increasing IFN-γ-producing CD4<sup>+</sup> and CD8<sup>+</sup> T cells. Ultimately, the AD-Exo vaccine reduced cardiac viral load, minimized histopathological damage, and significantly improved survival in challenged mice. This strategy provided novel perspectives for the development of dual-targeting prophylactic vaccines against viral myocarditis.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"70 ","pages":"Article 102865"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nanoparticle delivery systems have been extensively investigated as novel therapeutic strategies to promote drug-resistant disease. These nanoparticle formulations demonstrated improved bioavailability and enhanced tissue targeting. Also, there is growing acceptance of the value of traditional Chinese medicine in fighting disease. In this study, combining the advantages of nanomedicine with the characteristics of the acidic inflammatory microenvironment of atherosclerosis, a nanoplasmonic platform encapsulating the unstable drug Sch was designed for the treatment of atherosclerotic lesions. pH-responsive nanocarriers, an acid-labile material of acetylated β-cyclodextrin (β-CD) (Ac-bCD) were synthesized by chemical modification of β-CD. The resulting nanoparticles loaded with Sch (Sch-NPs) were prepared using a solvent evaporation method. In ApoE−/− mice fed a high-fat diet, Sch-NPs alleviated arterial damage, inhibited lipid metabolism disorders, reduced plaque area, and promoted plaque stability. In addition, Sch-NPs effectively reduced inflammatory infiltration and oxidative stress by modulating the MAPK pathway. Our findings demonstrate the promising applications of pH-responsive nanoparticles loaded with Sch for enhanced disease therapies such as atherosclerosis.
{"title":"Schisandrin-loaded β-cyclodextrin nanoparticles for atherosclerosis therapy","authors":"Qiuxia Huang, Xinyao Liu, Jinjin Yu, Xinya Zhang, Siqi Wang, Lili Zhou, Xiaofeng Niu, Weifeng Li","doi":"10.1016/j.nano.2025.102866","DOIUrl":"10.1016/j.nano.2025.102866","url":null,"abstract":"<div><div>Nanoparticle delivery systems have been extensively investigated as novel therapeutic strategies to promote drug-resistant disease. These nanoparticle formulations demonstrated improved bioavailability and enhanced tissue targeting. Also, there is growing acceptance of the value of traditional Chinese medicine in fighting disease. In this study, combining the advantages of nanomedicine with the characteristics of the acidic inflammatory microenvironment of atherosclerosis, a nanoplasmonic platform encapsulating the unstable drug Sch was designed for the treatment of atherosclerotic lesions. pH-responsive nanocarriers, an acid-labile material of acetylated β-cyclodextrin (β-CD) (Ac-bCD) were synthesized by chemical modification of β-CD. The resulting nanoparticles loaded with Sch (Sch-NPs) were prepared using a solvent evaporation method. In ApoE<sup>−/−</sup> mice fed a high-fat diet, Sch-NPs alleviated arterial damage, inhibited lipid metabolism disorders, reduced plaque area, and promoted plaque stability. In addition, Sch-NPs effectively reduced inflammatory infiltration and oxidative stress by modulating the MAPK pathway. Our findings demonstrate the promising applications of pH-responsive nanoparticles loaded with Sch for enhanced disease therapies such as atherosclerosis.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"70 ","pages":"Article 102866"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-10-22DOI: 10.1016/j.nano.2025.102872
Louisa Herbsleb , David Wild , Henriette Gröger , Tim Schubert , Anna Maria Steyer , Julian Hennies , Frauke Alves , Claus Feldmann , Andreas Walter
Inorganic–organic hybrid nanoparticles (IOH-NPs) are a promising drug delivery system in oncology due to their high drug-load capacity. In this study, we established a 3D correlative light and electron microscopy (CLEM) workflow that combines confocal fluorescence microscopy (FM) with focused ion beam scanning electron microscopy (FIBSEM) to unambiguously identify and visualize the (sub)cellular uptake and processing of reference fluorescently labeled and zirconium-based IOH-NPs in murine H8N8 breast cancer cells. The 3D-CLEM workflow was set up without the need to add external fiducial markers since image correlation was achieved using lipid droplets as intrinsic correlative landmarks. We observed that all H8N8 breast cancer cells had taken up IOH-NPs after 4 h, and most IOH-NPs were found in clusters within the H8N8 cells. IOH-NPs were internalized by endocytosis within 2 h with increasing cellular concentrations over time and accumulated in endolysosomal vesicles over 24 h, while the overall endolysosomal volume increased between 2 and 6 h after IOH-NP incubation and returned to its original value thereafter, remaining stable for up to 48 h. The 3D-CLEM workflow also revealed changes in the morphology and density of the IOH-NPs inside endolysosomal vesicles, suggesting the dissolution of IOH-NPs after 2 h. We also observed mitochondrial swelling in IOH-NP exposed cells, suggesting stress responses even without drug load. The 3D-CLEM workflow provides new insights into the cellular tracking and processing of IOH-NPs and supports the development of novel nanomedicine strategies.
无机-有机杂化纳米颗粒（IOH-NPs）因其高载药量而成为一种很有前途的肿瘤药物递送系统。在这项研究中，我们建立了三维相关光学和电子显微镜（CLEM）工作流程，结合共聚焦荧光显微镜（FM）和聚焦离子束扫描电子显微镜（FIBSEM），明确地识别和可视化小鼠H8N8乳腺癌细胞中参考荧光标记和锆基IOH-NPs的（亚）细胞摄取和加工。3D-CLEM工作流程的建立无需添加外部基准标记，因为使用脂滴作为内在相关标记实现了图像相关性。我们观察到，在4 h (h)后，所有H8N8乳腺癌细胞都吸收了IOH-NPs，并且大多数IOH-NPs在H8N8细胞内呈簇状分布。IOH-NP在2 h内通过内吞作用内化，随着时间的推移细胞浓度增加，并在24 h内积聚在内溶酶体囊泡中，而IOH-NP孵育后的2至6 h内溶酶体总体体积增加，此后恢复到初始值，保持稳定长达48 h。3D-CLEM工作流程还揭示了内溶酶体囊泡内IOH-NPs的形态和密度的变化，表明IOH-NPs在2 h后溶解。我们还观察到IOH-NP暴露细胞的线粒体肿胀，表明即使没有药物负荷也会出现应激反应。3D-CLEM工作流程为IOH-NPs的细胞跟踪和处理提供了新的见解，并支持了新型纳米医学策略的开发。
{"title":"3D correlative light and electron microscopy reveals the uptake and processing of inorganic-organic hybrid nanoparticles into cancer cells","authors":"Louisa Herbsleb , David Wild , Henriette Gröger , Tim Schubert , Anna Maria Steyer , Julian Hennies , Frauke Alves , Claus Feldmann , Andreas Walter","doi":"10.1016/j.nano.2025.102872","DOIUrl":"10.1016/j.nano.2025.102872","url":null,"abstract":"<div><div>Inorganic–organic hybrid nanoparticles (IOH-NPs) are a promising drug delivery system in oncology due to their high drug-load capacity. In this study, we established a 3D correlative light and electron microscopy (CLEM) workflow that combines confocal fluorescence microscopy (FM) with focused ion beam scanning electron microscopy (FIBSEM) to unambiguously identify and visualize the (sub)cellular uptake and processing of reference fluorescently labeled and zirconium-based IOH-NPs in murine H8N8 breast cancer cells. The 3D-CLEM workflow was set up without the need to add external fiducial markers since image correlation was achieved using lipid droplets as intrinsic correlative landmarks. We observed that all H8N8 breast cancer cells had taken up IOH-NPs after 4 h, and most IOH-NPs were found in clusters within the H8N8 cells. IOH-NPs were internalized by endocytosis within 2 h with increasing cellular concentrations over time and accumulated in endolysosomal vesicles over 24 h, while the overall endolysosomal volume increased between 2 and 6 h after IOH-NP incubation and returned to its original value thereafter, remaining stable for up to 48 h. The 3D-CLEM workflow also revealed changes in the morphology and density of the IOH-NPs inside endolysosomal vesicles, suggesting the dissolution of IOH-NPs after 2 h. We also observed mitochondrial swelling in IOH-NP exposed cells, suggesting stress responses even without drug load. The 3D-CLEM workflow provides new insights into the cellular tracking and processing of IOH-NPs and supports the development of novel nanomedicine strategies.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"70 ","pages":"Article 102872"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aims to investigate the anticancer properties of capsaicin, the active substance of red pepper, in different concentrations (2 %, 6 %, and 10 %) by chitosan and polyvinyl alcohol nanofiber substrate, against the K562 leukemia cell line. For this purpose, chitosan (Cs) and polyvinyl alcohol (PVA) polymers were used to produce nanofibers with a 20/80 ratio by electrospinning, with capsaicin serving as the anticancer drug. The properties of the fabricated nanofibers were evaluated by field emission scanning electron microscopy. Also, gold nanoparticles were used to analyze and compare its effectiveness against the K562 cancer cell line. This cell line was prepared from Pasteur cell bank and cultured in DMEM medium. Subsequently, the anticancer effect of synthetic nanofibers in different concentrations was assessed by performing survival test, apoptosis by annexin and propidium iodide staining, and cell scratch assay. The electron microscopy study demonstrated the uniformity and purity of the nanofiber structure. The results showed that capsaicin, dose-dependently, reduced the viability of K562 cells after 72 h (P < 0.01). The apoptotic assay also indicated that the induction of apoptosis significantly increased by PVA/Cs/Caps(2 %) and PVA/Cs/Au(5 %)/Caps(10 %) compounds in the studied cell line (P < 0.0001). Furthermore, scratch assay at 24, 48, and 72 h demonstrated that the mentioned compounds possess anti-migration potential, particularly at 48 h. Our results suggest that capsaicin in nanofiber substrate can show anticancer properties against the K562 leukemia cell line. Therefore, this compound can be considered a potential candidate for the treatment of leukemia.
以壳聚糖和聚乙乙醇纳米纤维为底物，研究不同浓度（2 %、6 %和10 %）的红辣椒活性物质辣椒素对K562白血病细胞的抗癌作用。为此，以壳聚糖（Cs）和聚乙烯醇（PVA）聚合物为原料，以辣椒素为抗癌药物，采用静电纺丝法制备了20/80比例的纳米纤维。利用场发射扫描电镜对制备的纳米纤维的性能进行了评价。此外，还利用金纳米颗粒对K562癌细胞的杀伤效果进行了分析和比较。该细胞系由巴斯德细胞库制备，在DMEM培养基中培养。随后，通过存活实验、膜联蛋白和碘化丙啶染色细胞凋亡实验和细胞划痕实验来评估不同浓度合成纳米纤维的抗癌作用。电镜研究表明，纳米纤维结构均匀，纯度高。结果表明，辣椒素在72 h (P
{"title":"Inhibition of growth of the human chronic leukemia cancer cell line K562 using capsaicin-containing nanofibers: an in vitro study","authors":"Mohadeseh Heidarzadeh , Habib Hamidinezhad , Fatemeh Hedayati Tabari , Mohammad Karimian","doi":"10.1016/j.nano.2025.102864","DOIUrl":"10.1016/j.nano.2025.102864","url":null,"abstract":"<div><div>This study aims to investigate the anticancer properties of capsaicin, the active substance of red pepper, in different concentrations (2 %, 6 %, and 10 %) by chitosan and polyvinyl alcohol nanofiber substrate, against the K562 leukemia cell line. For this purpose, chitosan (Cs) and polyvinyl alcohol (PVA) polymers were used to produce nanofibers with a 20/80 ratio by electrospinning, with capsaicin serving as the anticancer drug. The properties of the fabricated nanofibers were evaluated by field emission scanning electron microscopy. Also, gold nanoparticles were used to analyze and compare its effectiveness against the K562 cancer cell line. This cell line was prepared from Pasteur cell bank and cultured in DMEM medium. Subsequently, the anticancer effect of synthetic nanofibers in different concentrations was assessed by performing survival test, apoptosis by annexin and propidium iodide staining, and cell scratch assay. The electron microscopy study demonstrated the uniformity and purity of the nanofiber structure. The results showed that capsaicin, dose-dependently, reduced the viability of K562 cells after 72 h (<em>P</em> < 0.01). The apoptotic assay also indicated that the induction of apoptosis significantly increased by PVA/Cs/Caps(2 %) and PVA/Cs/Au(5 %)/Caps(10 %) compounds in the studied cell line (<em>P</em> < 0.0001). Furthermore, scratch assay at 24, 48, and 72 h demonstrated that the mentioned compounds possess anti-migration potential, particularly at 48 h. Our results suggest that capsaicin in nanofiber substrate can show anticancer properties against the K562 leukemia cell line. Therefore, this compound can be considered a potential candidate for the treatment of leukemia.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"70 ","pages":"Article 102864"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Metal nanoparticles (NPs) have emerged as advanced drug delivery systems, combining high therapeutic potential with complex safety considerations. Their unique physicochemical features, including high surface-to-volume ratios, tunable surfaces, and the ability to cross biological barriers, enable applications in targeted drug delivery and theranostics. Gold (Au), silver (Ag), iron oxide (Fe₃O₄), zinc oxide (ZnO), and platinum (Pt) NPs demonstrate outstanding efficacy: AuNPs achieve >90 % drug loading and 3–5× improved tumour targeting, AgNPs show up to 99 % antimicrobial activity, and Fe₃O₄ NPs function as both drug carriers and MRI contrast agents. However, toxicity remains a major hurdle. Reported challenges include dose-dependent cytotoxicity (IC₅₀: 10–40 μg/mL), hepatic retention (30–40 %), oxidative stress (2–10× ROS increase), and immune activation (up to 3-fold cytokine elevation). Safety is governed by physicochemical properties, with <10 nm NPs showing efficient penetration but higher genotoxicity, and cationic surfaces being 2–3× more cytotoxic. Several strategies have been developed to overcome these barriers. PEGylation reduces macrophage uptake by 60–75 % and extends circulation time, biodegradable hybrids reduce long-term accumulation by 70–80 %, and controlled-release systems cut doses by 30–50 % without compromising efficacy. Advances in computational tools, such as machine learning (~87 % predictive accuracy), along with standardized testing (<20 % variability), have accelerated preclinical evaluation by 40–50 %. These improvements contribute to therapeutic indices >10 and Phase I trial success rates of 65–75 %, significantly outperforming first-generation nanocarriers. This review highlights the need for multidisciplinary integration of nanotechnology, toxicology, computational modelling, and regulatory frameworks. With continued innovation, metal NPs hold the potential to revolutionize precision medicine through safer, scalable, and clinically translatable nanoplatforms.
{"title":"Therapeutic potential and toxicological challenges of metal nanoparticles in drug delivery: A comprehensive review","authors":"Sajid Mehmood , Sajiya Iraqui , Rajesh Kumar Ojha , Nisha Sharma , Ab Rahman Marlinda","doi":"10.1016/j.nano.2025.102862","DOIUrl":"10.1016/j.nano.2025.102862","url":null,"abstract":"<div><div>Metal nanoparticles (NPs) have emerged as advanced drug delivery systems, combining high therapeutic potential with complex safety considerations. Their unique physicochemical features, including high surface-to-volume ratios, tunable surfaces, and the ability to cross biological barriers, enable applications in targeted drug delivery and theranostics. Gold (Au), silver (Ag), iron oxide (Fe₃O₄), zinc oxide (ZnO), and platinum (Pt) NPs demonstrate outstanding efficacy: AuNPs achieve >90 % drug loading and 3–5× improved tumour targeting, AgNPs show up to 99 % antimicrobial activity, and Fe₃O₄ NPs function as both drug carriers and MRI contrast agents. However, toxicity remains a major hurdle. Reported challenges include dose-dependent cytotoxicity (IC₅₀: 10–40 μg/mL), hepatic retention (30–40 %), oxidative stress (2–10× ROS increase), and immune activation (up to 3-fold cytokine elevation). Safety is governed by physicochemical properties, with <10 nm NPs showing efficient penetration but higher genotoxicity, and cationic surfaces being 2–3× more cytotoxic. Several strategies have been developed to overcome these barriers. PEGylation reduces macrophage uptake by 60–75 % and extends circulation time, biodegradable hybrids reduce long-term accumulation by 70–80 %, and controlled-release systems cut doses by 30–50 % without compromising efficacy. Advances in computational tools, such as machine learning (~87 % predictive accuracy), along with standardized testing (<20 % variability), have accelerated preclinical evaluation by 40–50 %. These improvements contribute to therapeutic indices >10 and Phase I trial success rates of 65–75 %, significantly outperforming first-generation nanocarriers. This review highlights the need for multidisciplinary integration of nanotechnology, toxicology, computational modelling, and regulatory frameworks. With continued innovation, metal NPs hold the potential to revolutionize precision medicine through safer, scalable, and clinically translatable nanoplatforms.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"70 ","pages":"Article 102862"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-11-05DOI: 10.1016/j.nano.2025.102873
Piyushkumar Sadhu , Mamta Kumari , Nirmal Shah , Niyati Shah , Chitrali Talele , Falguni Rathod
{"title":"A state-of-the-art review on inhalable nanoconjugates for targeted drug delivery in acute lung injury: Advances, challenges and future directions","authors":"Piyushkumar Sadhu , Mamta Kumari , Nirmal Shah , Niyati Shah , Chitrali Talele , Falguni Rathod","doi":"10.1016/j.nano.2025.102873","DOIUrl":"10.1016/j.nano.2025.102873","url":null,"abstract":"","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"70 ","pages":"Article 102873"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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