Pub Date : 2025-11-23DOI: 10.1016/j.nano.2025.102879
Sung-Ho Shin , Dhushyanth Viswanath , Haley A. Harper , Sandra E. Torregrosa-Allen , Carli J. McMahan , Alex E. Schwimmer , Bennett D. Elzey , You-Yeon Won
Radioluminescent nanoparticles enable radiotherapy- or X-ray-triggered photodynamic therapy (RT-PDT, also referred to as X-PDT in the literature) using the 5-aminolevulinic acid (ALA) prodrug, thereby overcoming the limited tissue penetration of conventional PDT. However, their therapeutic efficacy remains constrained by poor intratumoral nanoparticle distribution. To address this challenge, we developed collagenase-functionalized calcium tungstate nanoparticles capable of enzymatically degrading the extracellular matrix (ECM) in solid tumors. Micro-CT imaging revealed that collagenase functionalization increased intratumoral nanoparticle distribution by approximately sevenfold. In vivo studies further showed that enhanced penetration improved NP delivery, but that surface-bound maleimide linkers and collagenase partially scavenged reactive oxygen species (ROS), revealing a trade-off between ECM degradation and the quenching of ROS-mediated photodynamic effects. Overall, these findings demonstrates that collagenase-functionalized radioluminescent nanoparticles can effectively overcome stromal barriers in collagen-rich solid tumors, providing a promising strategy for next-generation RT-PDT while underscoring the importance of balancing enzymatic ECM remodeling with preservation of ROS generation.
{"title":"Enhancing intratumoral spread of radioluminescent nanoparticles via collagenase functionalization for radiation-induced photodynamic cancer therapy","authors":"Sung-Ho Shin , Dhushyanth Viswanath , Haley A. Harper , Sandra E. Torregrosa-Allen , Carli J. McMahan , Alex E. Schwimmer , Bennett D. Elzey , You-Yeon Won","doi":"10.1016/j.nano.2025.102879","DOIUrl":"10.1016/j.nano.2025.102879","url":null,"abstract":"<div><div>Radioluminescent nanoparticles enable radiotherapy- or X-ray-triggered photodynamic therapy (RT-PDT, also referred to as X-PDT in the literature) using the 5-aminolevulinic acid (ALA) prodrug, thereby overcoming the limited tissue penetration of conventional PDT. However, their therapeutic efficacy remains constrained by poor intratumoral nanoparticle distribution. To address this challenge, we developed collagenase-functionalized calcium tungstate nanoparticles capable of enzymatically degrading the extracellular matrix (ECM) in solid tumors. Micro-CT imaging revealed that collagenase functionalization increased intratumoral nanoparticle distribution by approximately sevenfold. <em>In vivo</em> studies further showed that enhanced penetration improved NP delivery, but that surface-bound maleimide linkers and collagenase partially scavenged reactive oxygen species (ROS), revealing a trade-off between ECM degradation and the quenching of ROS-mediated photodynamic effects. Overall, these findings demonstrates that collagenase-functionalized radioluminescent nanoparticles can effectively overcome stromal barriers in collagen-rich solid tumors, providing a promising strategy for next-generation RT-PDT while underscoring the importance of balancing enzymatic ECM remodeling with preservation of ROS generation.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102879"},"PeriodicalIF":4.6,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145605120","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 : 2025-11-20DOI: 10.1016/j.nano.2025.102880
Lydia-Nefeli Thrapsanioti , Andrey N. Kuskov , Aikaterini Berdiaki , Anna L. Luss , Elizaveta R. Vlaskina , Anna V. Ivanova , Maxim A. Abakumov , Maria Marmara , Kalliope Plexousaki , Aristides Tsatsakis , Dragana Nikitovic
Iron oxide nanoparticles (IONPs) offer promise for drug delivery and imaging, but their vascular safety requires thorough evaluation. Hydroxyethyl starch (HES) is a clinically used, biocompatible polysaccharide with potential as a nanoparticle coating to improve vascular safety. We synthesized novel hydroxyethyl starch-coated IONPs (IONPs@HES) and assessed their properties and effects on human microvascular endothelial cells (HMEC-1) under basal and inflammatory conditions. IONPs@HES showed magnetite cores, near-neutral charge, and reduced magnetic saturation, supporting biocompatibility. They were efficiently internalized without affecting viability or proliferation (20–500 μg/mL) and did not increase LPS-induced ICAM-1 expression. Autophagic activity, assessed by LC3 immunofluorescence and Cyto-ID flow cytometry, remained unchanged, suggesting preserved autophagic homeostasis. A modest increase in phosphorylated caveolin-1 (p-CAV1) was observed, with no enhancement under LPS stimulation. Co-treatment with indomethacin showed no additive toxicity. These findings support IONPs@HES as a biocompatible nanoplatform suitable for vascular-targeted cancer therapy, meriting further in vivo validation.
{"title":"Tailored iron oxide nanoparticles for biomedical applications: Hydroxyethyl starch coating enhances endothelial biocompatibility","authors":"Lydia-Nefeli Thrapsanioti , Andrey N. Kuskov , Aikaterini Berdiaki , Anna L. Luss , Elizaveta R. Vlaskina , Anna V. Ivanova , Maxim A. Abakumov , Maria Marmara , Kalliope Plexousaki , Aristides Tsatsakis , Dragana Nikitovic","doi":"10.1016/j.nano.2025.102880","DOIUrl":"10.1016/j.nano.2025.102880","url":null,"abstract":"<div><div>Iron oxide nanoparticles (IONPs) offer promise for drug delivery and imaging, but their vascular safety requires thorough evaluation. Hydroxyethyl starch (HES) is a clinically used, biocompatible polysaccharide with potential as a nanoparticle coating to improve vascular safety. We synthesized novel hydroxyethyl starch-coated IONPs (IONPs@HES) and assessed their properties and effects on human microvascular endothelial cells (HMEC-1) under basal and inflammatory conditions. IONPs@HES showed magnetite cores, near-neutral charge, and reduced magnetic saturation, supporting biocompatibility. They were efficiently internalized without affecting viability or proliferation (20–500 μg/mL) and did not increase LPS-induced ICAM-1 expression. Autophagic activity, assessed by LC3 immunofluorescence and Cyto-ID flow cytometry, remained unchanged, suggesting preserved autophagic homeostasis. A modest increase in phosphorylated caveolin-1 (p-CAV1) was observed, with no enhancement under LPS stimulation. Co-treatment with indomethacin showed no additive toxicity. These findings support IONPs@HES as a biocompatible nanoplatform suitable for vascular-targeted cancer therapy, meriting further in vivo validation.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102880"},"PeriodicalIF":4.6,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577788","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 : 2025-11-18DOI: 10.1016/j.nano.2025.102878
Tariq Fahmi , Robert Gutierrez , Ana C. Barrios , Tae Joon Cho , John T. Elliott , Sanghamitra Majumdar , Bryant C. Nelson , Aaron C. Johnston-Peck , Alessandro Tona , Anil K. Patri , Elijah J. Petersen
Assays to detect potential biocompatibility issues can play a key role in supporting the development of new technologies such as medical products containing engineered nanomaterials (ENMs). A consensus test method standard on nitric oxide production after cellular ENM exposure was developed and published through ASTM International. In this paper, we describe an evaluation of sources of variability in this method. A significant challenge is ensuring that the protocol contains the necessary control measurements to account for potential issues when testing ENMs. Protocol testing was conducted during draft standard development and post-publication to better understand potential sources of variability such as the impact of insufficient removal of the ENM, the number of cells seeded, the selection of positive control compounds, and the culture techniques of the cells prior to the experiments. Several in-process control measurements were used to monitor the performance of intermediate steps in the assay procedure. Two gold nanoparticles with different surface coatings and nano-sized polystyrene particles were used to demonstrate the applicability of some of the control measurements. This testing revealed which sources of variability were more likely to have a significant impact on the overall assay uncertainty and confirmed the key importance of certain control measurements. These results could also support the standardization of other ENM-related in vitro methods that share similarities in their protocols with the method investigated here. The further development of this method can also support its use to evaluate the potential for substances other than ENMs to induce nitric oxide production.
{"title":"Evaluation of sources of variability in a nitric oxide screening assay for engineered nanomaterials","authors":"Tariq Fahmi , Robert Gutierrez , Ana C. Barrios , Tae Joon Cho , John T. Elliott , Sanghamitra Majumdar , Bryant C. Nelson , Aaron C. Johnston-Peck , Alessandro Tona , Anil K. Patri , Elijah J. Petersen","doi":"10.1016/j.nano.2025.102878","DOIUrl":"10.1016/j.nano.2025.102878","url":null,"abstract":"<div><div>Assays to detect potential biocompatibility issues can play a key role in supporting the development of new technologies such as medical products containing engineered nanomaterials (ENMs). A consensus test method standard on nitric oxide production after cellular ENM exposure was developed and published through ASTM International. In this paper, we describe an evaluation of sources of variability in this method. A significant challenge is ensuring that the protocol contains the necessary control measurements to account for potential issues when testing ENMs. Protocol testing was conducted during draft standard development and post-publication to better understand potential sources of variability such as the impact of insufficient removal of the ENM, the number of cells seeded, the selection of positive control compounds, and the culture techniques of the cells prior to the experiments. Several in-process control measurements were used to monitor the performance of intermediate steps in the assay procedure. Two gold nanoparticles with different surface coatings and nano-sized polystyrene particles were used to demonstrate the applicability of some of the control measurements. This testing revealed which sources of variability were more likely to have a significant impact on the overall assay uncertainty and confirmed the key importance of certain control measurements. These results could also support the standardization of other ENM-related <em>in vitro</em> methods that share similarities in their protocols with the method investigated here. The further development of this method can also support its use to evaluate the potential for substances other than ENMs to induce nitric oxide production.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102878"},"PeriodicalIF":4.6,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564896","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 : 2025-11-11DOI: 10.1016/j.nano.2025.102876
Alshayma N. Al-Thani , Asma Ghafoor Jan , Zainab Hajialthakar , Nada Aakel , Mohamed Abbas
This review delves into the intricacies of Photodynamic Therapy (PDT), focusing on mechanisms such as the accumulation of selective photosensitizers and the generation of Reactive Oxygen Species (ROS). Research is investigating the use of zirconium oxide nanoparticles (ZrO2 NPs) and their combination with upconversion nanoparticles. The functionalization of ZrO2 NPs is stressed for targeted drug administration and enhanced therapeutic effects. Addressing PDT challenges, ZrO2 NPs exhibit potential to enhance treatment accuracy, minimize side effects, and improve overall success. Supported by preclinical and clinical research, zirconium-based PDT emerges as a transformative cancer therapy technique. Integrating ZrO2 NPs into PDT represents a groundbreaking approach, allowing selective cancer cell targeting and promising improved treatment outcomes and synergies with other modalities. With demonstrated safety and efficacy, ZrO2 PDT constitutes a vital component in advancing cancer patient outcomes globally.
{"title":"Zirconium oxide nanoparticles in advancing photodynamic therapy for cancer treatment","authors":"Alshayma N. Al-Thani , Asma Ghafoor Jan , Zainab Hajialthakar , Nada Aakel , Mohamed Abbas","doi":"10.1016/j.nano.2025.102876","DOIUrl":"10.1016/j.nano.2025.102876","url":null,"abstract":"<div><div>This review delves into the intricacies of Photodynamic Therapy (PDT), focusing on mechanisms such as the accumulation of selective photosensitizers and the generation of Reactive Oxygen Species (ROS). Research is investigating the use of zirconium oxide nanoparticles (ZrO<sub>2</sub> NPs) and their combination with upconversion nanoparticles. The functionalization of ZrO<sub>2</sub> NPs is stressed for targeted drug administration and enhanced therapeutic effects. Addressing PDT challenges, ZrO<sub>2</sub> NPs exhibit potential to enhance treatment accuracy, minimize side effects, and improve overall success. Supported by preclinical and clinical research, zirconium-based PDT emerges as a transformative cancer therapy technique. Integrating ZrO<sub>2</sub> NPs into PDT represents a groundbreaking approach, allowing selective cancer cell targeting and promising improved treatment outcomes and synergies with other modalities. With demonstrated safety and efficacy, ZrO<sub>2</sub> PDT constitutes a vital component in advancing cancer patient outcomes globally.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102876"},"PeriodicalIF":4.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513303","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 : 2025-11-10DOI: 10.1016/j.nano.2025.102875
Muhammad Sohail , Mahtab Mirbolouk
The beneficial physical, chemical, and biological properties of proteins make them useful building blocks in the construction of biomedicals and nanomaterials. There are various biomaterials to develop inventive drug delivery systems ranging from simple to complex proteins which can be more efficient for patients undergoing surgical procedures. In the line of this article, the definition of medicine via proteins is based on complex bioengineering systems that mix tailored biomaterials with molecular algorithms to form controlled bioactive nanosystems. Among biomaterials, proteins are unique, because they can be found directly in nature, which qualify them easy for use, especially in surgical procedures. This article is aimed at describing their origin, structural properties, functions characteristics of interest in biology, and activity as drug delivery systems. Their native form and form of biomaterials i.e., hydrogels, scaffolds, membranes, fibers, and nanoparticles are examined. The article discusses novel designed nanoarchitectures aimed to solve long lasting problems in drug delivery like poor drug solubility, low bioavailability, and encapsulation of active pharmaceutical ingredients (APIs). The most important innovations are systems that respond to stimuli, mucoadhesive and mucus penetrating structures, lymphatic-targeting designs, and carriers that respond to environmental changes. Moreover, the article outlines the therapeutic uses of biomaterials based on proteins in tissue engineering (bone, cartilage, skin, cardiac, and neural tissue engineering), cancer treatment, diabetes, gene therapy, and in the treatment of inflammatory and chronically symptomatic disorders. Each part is arranged to minimize overlap and highlight functional distinctiveness to provide a cohesive design that integrates structure, function, and use. The review ends with the discussion of the existing gaps and the proposed pathways for future investigations which could facilitate the clinical translation of the work. This work serves as a stimulus toward the rational conception of protein-based materials and designed nanocarriers which are structurally tailored and application-driven, increasing their impact in the fields of drug delivery and regenerative medicine.
{"title":"Protein-based biomaterials: Advances in structural design for drug delivery and regenerative medicine","authors":"Muhammad Sohail , Mahtab Mirbolouk","doi":"10.1016/j.nano.2025.102875","DOIUrl":"10.1016/j.nano.2025.102875","url":null,"abstract":"<div><div>The beneficial physical, chemical, and biological properties of proteins make them useful building blocks in the construction of biomedicals and nanomaterials. There are various biomaterials to develop inventive drug delivery systems ranging from simple to complex proteins which can be more efficient for patients undergoing surgical procedures. In the line of this article, the definition of medicine via proteins is based on complex bioengineering systems that mix tailored biomaterials with molecular algorithms to form controlled bioactive nanosystems. Among biomaterials, proteins are unique, because they can be found directly in nature, which qualify them easy for use, especially in surgical procedures. This article is aimed at describing their origin, structural properties, functions characteristics of interest in biology, and activity as drug delivery systems. Their native form and form of biomaterials i.e., hydrogels, scaffolds, membranes, fibers, and nanoparticles are examined. The article discusses novel designed nanoarchitectures aimed to solve long lasting problems in drug delivery like poor drug solubility, low bioavailability, and encapsulation of active pharmaceutical ingredients (APIs). The most important innovations are systems that respond to stimuli, mucoadhesive and mucus penetrating structures, lymphatic-targeting designs, and carriers that respond to environmental changes. Moreover, the article outlines the therapeutic uses of biomaterials based on proteins in tissue engineering (bone, cartilage, skin, cardiac, and neural tissue engineering), cancer treatment, diabetes, gene therapy, and in the treatment of inflammatory and chronically symptomatic disorders. Each part is arranged to minimize overlap and highlight functional distinctiveness to provide a cohesive design that integrates structure, function, and use. The review ends with the discussion of the existing gaps and the proposed pathways for future investigations which could facilitate the clinical translation of the work. This work serves as a stimulus toward the rational conception of protein-based materials and designed nanocarriers which are structurally tailored and application-driven, increasing their impact in the fields of drug delivery and regenerative medicine.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102875"},"PeriodicalIF":4.6,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145479128","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 : 2025-11-01DOI: 10.1016/j.nano.2025.102874
Zainab Lafi , Sherine Asha , Nisreen Asha
Epilepsy is a chronic neurological disorder marked by recurrent, unprovoked seizures that can lead to cognitive impairment, psychiatric comorbidities, and reduced quality of life. While seizure control is critical for minimizing long-term neurological harm, conventional antiseizure medications (ASMs) are often hindered by limited brain penetration, systemic toxicity, and pharmacoresistance. Liposomal drug delivery systems offer a promising approach to overcome these limitations by enhancing central nervous system targeting, improving drug solubility and stability, and reducing off-target effects. Recent advances in surface-functionalized and immunoliposomes support site-specific delivery to epileptogenic regions and neuroinflammatory targets, contributing to more precise and better-tolerated therapies. Despite encouraging progress, important challenges remain in formulation optimization, targeting specificity, and clinical translation. Continued refinement of liposomal platforms may significantly advance personalized and effective epilepsy management.
{"title":"Liposomes for epilepsy treatment: Toward better brain targeting and reduced toxicity","authors":"Zainab Lafi , Sherine Asha , Nisreen Asha","doi":"10.1016/j.nano.2025.102874","DOIUrl":"10.1016/j.nano.2025.102874","url":null,"abstract":"<div><div>Epilepsy is a chronic neurological disorder marked by recurrent, unprovoked seizures that can lead to cognitive impairment, psychiatric comorbidities, and reduced quality of life. While seizure control is critical for minimizing long-term neurological harm, conventional antiseizure medications (ASMs) are often hindered by limited brain penetration, systemic toxicity, and pharmacoresistance. Liposomal drug delivery systems offer a promising approach to overcome these limitations by enhancing central nervous system targeting, improving drug solubility and stability, and reducing off-target effects. Recent advances in surface-functionalized and immunoliposomes support site-specific delivery to epileptogenic regions and neuroinflammatory targets, contributing to more precise and better-tolerated therapies. Despite encouraging progress, important challenges remain in formulation optimization, targeting specificity, and clinical translation. Continued refinement of liposomal platforms may significantly advance personalized and effective epilepsy management.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"70 ","pages":"Article 102874"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452520","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 : 2025-11-01DOI: 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 : 2025-11-01DOI: 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 : 2025-11-01DOI: 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。
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Pub Date : 2025-11-01DOI: 10.1016/j.nano.2025.102873
Piyushkumar Sadhu , Mamta Kumari , Nirmal Shah , Niyati Shah , Chitrali Talele , Falguni Rathod
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