Nataliya Kavok, , , Galyna Dudetskaya, , , Vladyslav Seminko*, , , Pavel Maksimchuk, , , Yurii Kot, , , Olga Sedyh, , , Kateryna Hubenko, , , Olga Vashchenko, , , Vladimir Klochkov, , and , Svetlana Yefimova,
Supramolecular complexes (SMCs) based on cholesterol, menadione, and redox-active ceria nanoparticles (NPs) with a pronounced antitumor effect triggered by the addition of ascorbic acid were obtained. Ascorbic acid plays the role of electron donor, increasing sufficiently the ability of ceria NPs in SMCs to oxidize thiol-containing biological molecules including glutathione and cysteine. The mechanism of the enhanced oxidizing ability of SMCs is based on the redox cycling of both ceria NPs and menadione with superoxide anions formed as an intermediate product. As a result of strong prooxidant activity, SMCs provide significant cytotoxicity toward mouse fibrosarcoma cells in 2D and 3D models accompanied by reduced cell viability, a decrease of the mitochondrial membrane potential, and cell shrinkage. The absence of such an effect on murine fibroblasts indicates that the cytotoxic action of an ascorbate–nanoceria pair is highly selective, targeting tumor cells but not nontumor ones.
{"title":"Ascorbate-Triggered Antitumor Activity of Nanoceria- and Ceria-Based Supramolecular Complexes in 2D and 3D Cell Cultures","authors":"Nataliya Kavok, , , Galyna Dudetskaya, , , Vladyslav Seminko*, , , Pavel Maksimchuk, , , Yurii Kot, , , Olga Sedyh, , , Kateryna Hubenko, , , Olga Vashchenko, , , Vladimir Klochkov, , and , Svetlana Yefimova, ","doi":"10.1021/acsabm.5c00916","DOIUrl":"10.1021/acsabm.5c00916","url":null,"abstract":"<p >Supramolecular complexes (SMCs) based on cholesterol, menadione, and redox-active ceria nanoparticles (NPs) with a pronounced antitumor effect triggered by the addition of ascorbic acid were obtained. Ascorbic acid plays the role of electron donor, increasing sufficiently the ability of ceria NPs in SMCs to oxidize thiol-containing biological molecules including glutathione and cysteine. The mechanism of the enhanced oxidizing ability of SMCs is based on the redox cycling of both ceria NPs and menadione with superoxide anions formed as an intermediate product. As a result of strong prooxidant activity, SMCs provide significant cytotoxicity toward mouse fibrosarcoma cells in 2D and 3D models accompanied by reduced cell viability, a decrease of the mitochondrial membrane potential, and cell shrinkage. The absence of such an effect on murine fibroblasts indicates that the cytotoxic action of an ascorbate–nanoceria pair is highly selective, targeting tumor cells but not nontumor ones.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 11","pages":"9730–9740"},"PeriodicalIF":4.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145456955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on “Remodeling the Tumor Microenvironment via Metal-Phenolic Network-Coated Poly(lactic acid-co-glycolic acid) Nanoparticles for Inducing Multimodal Combination Therapy in Non-Small Cell Lung Cancer”","authors":"Haris Afridi*, and , Muqadas Khosa, ","doi":"10.1021/acsabm.5c01273","DOIUrl":"10.1021/acsabm.5c01273","url":null,"abstract":"","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 11","pages":"9512–9513"},"PeriodicalIF":4.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuchen Rui, , , Dallin Arnold, , , Jacob L. Beckham, , , Bowen Li, , , Guillaume Duret, , , Gautam Chaudhry, , , Jacob T. Robinson*, , and , James M. Tour*,
Precise remote control of skeletal muscle contraction could be beneficial to the study and treatment of muscular dysfunction. Recently, we reported a method regulating intracellular calcium signaling using molecular motors (MMs), molecules that rotate submolecular components unidirectionally upon absorption of light. Here, we explore the application of this methodology to skeletal muscle tissue. Our results demonstrate that MMs induce intracellular calcium release in C2C12 myoblasts and differentiated myotubes via IP3-mediated signaling in a fashion that depends on their fast unidirectional rotation. Inhibition of proteins involved in the cAMP pathway such as adenylyl cyclase and protein kinase A also reduced the magnitude of the elicited calcium responses. We further show that, in differentiated C2C12 myotubes, the calcium signaling events driven by MM activation cause localized myotube contraction. This work demonstrates the use of a molecular mechanical technique to directly control skeletal muscle contraction, expanding the scope of available tools to study muscle contraction in a single-cell regime and treat a range of myopathies.
{"title":"Molecular Motors Activate Skeletal Muscle","authors":"Yuchen Rui, , , Dallin Arnold, , , Jacob L. Beckham, , , Bowen Li, , , Guillaume Duret, , , Gautam Chaudhry, , , Jacob T. Robinson*, , and , James M. Tour*, ","doi":"10.1021/acsabm.5c01450","DOIUrl":"10.1021/acsabm.5c01450","url":null,"abstract":"<p >Precise remote control of skeletal muscle contraction could be beneficial to the study and treatment of muscular dysfunction. Recently, we reported a method regulating intracellular calcium signaling using molecular motors (MMs), molecules that rotate submolecular components unidirectionally upon absorption of light. Here, we explore the application of this methodology to skeletal muscle tissue. Our results demonstrate that MMs induce intracellular calcium release in C2C12 myoblasts and differentiated myotubes via IP<sub>3</sub>-mediated signaling in a fashion that depends on their fast unidirectional rotation. Inhibition of proteins involved in the cAMP pathway such as adenylyl cyclase and protein kinase A also reduced the magnitude of the elicited calcium responses. We further show that, in differentiated C2C12 myotubes, the calcium signaling events driven by MM activation cause localized myotube contraction. This work demonstrates the use of a molecular mechanical technique to directly control skeletal muscle contraction, expanding the scope of available tools to study muscle contraction in a single-cell regime and treat a range of myopathies.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 11","pages":"10090–10100"},"PeriodicalIF":4.7,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
So Eun Kim, , , Shanmugam Sureshkumar, , , Hak Yong Kim, , , Alagan Muthurasu*, , and , Jae Chol Yoon*,
A highly sensitive and selective electrochemical immunosensor was developed for the detection of the cancer biomarker alpha-fetoprotein (AFP), a key indicator of cancer. This sensor utilizes the enhanced electrochemical current response generated by a composite material consisting of gold nanoparticles (Au NPs) decorated on a metal–organic framework (MOF) containing iron and cobalt (FeCo). The Au NP-decorated FeCo-based MOF labeled with primary antibodies (Ab1) significantly enhances the electrochemical response, enabling accurate detection of AFP. Similarly, HRP–Au nanoprism (Au NPR) nanocomposites were prepared via a one-pot assembly, where horseradish peroxidase (HRP) and the secondary antibody (Ab2) were coimmobilized on Au NPRs to form a stable nanocomposite. The immunosensor was fabricated by assembling Au NPs@ FeCo-MOF and capture antibodies (Ab1) onto a glassy carbon electrode. The MOF served as a conductive matrix, AuNPs enhanced electron transfer, and Ab1 ensured specific antigen recognition. When the AFP antigen is present, labeled Ab2 binds to the Au NP-decorated FeCo-MOF via specific antigen–antibody interactions, leading to enhanced electrochemical signals for sensitive detection. The immunosensor response was measured by differential pulse voltammetry (DPV) in phosphate-buffered solution (PBS) containing hydrogen peroxide (H2O2) and 3,3′,5,5′-tetramethylbenzidine (TMB). Under controlled conditions, the immunosensor exhibited a linear response to AFP over the range of 0.0001 to 100 ng mL–1, with a detection limit of 1.2 pg mL–1 (S/N = 3), indicating high sensitivity. The immunosensor’s performance was validated by detecting AFP in human serum samples, demonstrating its potential for ultrasensitive detection of AFP and other biomarkers.
{"title":"Electrochemical Sensitive Detection of Alpha-Fetoprotein Using HRP-Gold Nanostructures on Fe–Co MOF-Derived Nanocomposites","authors":"So Eun Kim, , , Shanmugam Sureshkumar, , , Hak Yong Kim, , , Alagan Muthurasu*, , and , Jae Chol Yoon*, ","doi":"10.1021/acsabm.5c01820","DOIUrl":"10.1021/acsabm.5c01820","url":null,"abstract":"<p >A highly sensitive and selective electrochemical immunosensor was developed for the detection of the cancer biomarker alpha-fetoprotein (AFP), a key indicator of cancer. This sensor utilizes the enhanced electrochemical current response generated by a composite material consisting of gold nanoparticles (Au NPs) decorated on a metal–organic framework (MOF) containing iron and cobalt (FeCo). The Au NP-decorated FeCo-based MOF labeled with primary antibodies (Ab<sub>1</sub>) significantly enhances the electrochemical response, enabling accurate detection of AFP. Similarly, HRP–Au nanoprism (Au NPR) nanocomposites were prepared via a one-pot assembly, where horseradish peroxidase (HRP) and the secondary antibody (Ab<sub>2</sub>) were coimmobilized on Au NPRs to form a stable nanocomposite. The immunosensor was fabricated by assembling Au NPs@ FeCo-MOF and capture antibodies (Ab<sub>1</sub>) onto a glassy carbon electrode. The MOF served as a conductive matrix, AuNPs enhanced electron transfer, and Ab<sub>1</sub> ensured specific antigen recognition. When the AFP antigen is present, labeled Ab<sub>2</sub> binds to the Au NP-decorated FeCo-MOF via specific antigen–antibody interactions, leading to enhanced electrochemical signals for sensitive detection. The immunosensor response was measured by differential pulse voltammetry (DPV) in phosphate-buffered solution (PBS) containing hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and 3,3′,5,5′-tetramethylbenzidine (TMB). Under controlled conditions, the immunosensor exhibited a linear response to AFP over the range of 0.0001 to 100 ng mL<sup>–1</sup>, with a detection limit of 1.2 pg mL<sup>–1</sup> (S/N = 3), indicating high sensitivity. The immunosensor’s performance was validated by detecting AFP in human serum samples, demonstrating its potential for ultrasensitive detection of AFP and other biomarkers.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 11","pages":"10472–10482"},"PeriodicalIF":4.7,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Long investigated for its physiological functions, glutamic acid (Glu) is a crucial amino acid implicated in plant development and stress responses. However, there is still limited in vivo monitoring of Glu. Here, we report the design of a “turn-on” fluorescence nanosensor for the selective detection of Glu: a nitrogen-doped carbon quantum dot (N-CQD)/Cu2+ complex. Cu2+ ions quenched the fluorescence of N-CQDs, which was then selectively recovered when Glu was added. This allowed for sensitive detection via a fluorescence recovery mechanism. The sensing technology showed outstanding selectivity, biocompatibility, and quick response. Dynamic quenching was verified as the underlying mechanism by characterization using FT-IR, XPS, DLS, and TCSPC. The uptake of N-CQDs and N-CQDs/Cu2+ complexes in Vigna radiata stem tissues was visualized by confocal laser scanning microscopy (CLSM), with preferential accumulation in the interfascicular, vascular bundle, and epidermal areas. Notably, Glu pretreatment affected the internalization of nanoparticles by modulating fluorescence intensity in a concentration-dependent manner. Remarkably, N-CQDs alone enhanced plant growth under LED light stress, indicating that they may function as regulators of plant development. These results offer a platform that can be used for the biological manipulation of glutamic acid in plants as well as real-time monitoring.
{"title":"Carbon Nanodots with Dual Capabilities: Glutamic Acid Sensor and Plant Growth Promoter under LED Stress Conditions","authors":"Tumpa Biswas, , , Shrodha Mondal, , , Olivia Sarkar, , , Ansuman Chattopadhyay, , and , Prithidipa Sahoo*, ","doi":"10.1021/acsabm.5c01777","DOIUrl":"10.1021/acsabm.5c01777","url":null,"abstract":"<p >Long investigated for its physiological functions, glutamic acid (Glu) is a crucial amino acid implicated in plant development and stress responses. However, there is still limited in vivo monitoring of Glu. Here, we report the design of a “turn-on” fluorescence nanosensor for the selective detection of Glu: a nitrogen-doped carbon quantum dot (N-CQD)/Cu<sup>2+</sup> complex. Cu<sup>2+</sup> ions quenched the fluorescence of N-CQDs, which was then selectively recovered when Glu was added. This allowed for sensitive detection via a fluorescence recovery mechanism. The sensing technology showed outstanding selectivity, biocompatibility, and quick response. Dynamic quenching was verified as the underlying mechanism by characterization using FT-IR, XPS, DLS, and TCSPC. The uptake of N-CQDs and N-CQDs/Cu<sup>2+</sup> complexes in <i>Vigna radiata</i> stem tissues was visualized by confocal laser scanning microscopy (CLSM), with preferential accumulation in the interfascicular, vascular bundle, and epidermal areas. Notably, Glu pretreatment affected the internalization of nanoparticles by modulating fluorescence intensity in a concentration-dependent manner. Remarkably, N-CQDs alone enhanced plant growth under LED light stress, indicating that they may function as regulators of plant development. These results offer a platform that can be used for the biological manipulation of glutamic acid in plants as well as real-time monitoring.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 11","pages":"10436–10444"},"PeriodicalIF":4.7,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The rising incidence of biliary diseases, driven by an aging population and lifestyle changes, has elevated the importance of biliary stenting. This review aimed to systematically evaluate recent advancements in biliary stent materials and coatings, assessing their role in treating biliary stenosis and obstruction, with an emphasis on multifunctional coatings to enhance stent safety, efficacy, and patient outcomes while minimizing complications. Antimicrobial coatings, such as those with silver ions or chitosan, reduce infection risk; drug-eluting coatings, incorporating antibiotics or paclitaxel, mitigate infection and tumor progression; antiadhesion coatings extend stent patency. Furthermore, 3D printing enables patient-specific stent designs for optimal fit, while smart stents with integrated sensors enhance therapeutic precision by monitoring biliary parameters in real time. Multifunctional coatings and advanced materials substantially improve biliary stent performance, offering safer and more effective treatment options for biliary diseases. This review synthesizes the advantages and challenges of current technologies and recommends that future research should prioritize smart stents, biodegradable materials, and multifunctional coatings, validating their long-term safety and efficacy through clinical trials to optimize patient outcomes and advance clinical applications.
{"title":"Research Progress on Biliary Stent Materials and Coatings","authors":"Ke Wang, , , Baosen Mi, , , Jingjing Wang, , , Ping Liu, , , Xun Ma, , , Tianju Chen, , and , Wei Li*, ","doi":"10.1021/acsabm.5c01650","DOIUrl":"10.1021/acsabm.5c01650","url":null,"abstract":"<p >The rising incidence of biliary diseases, driven by an aging population and lifestyle changes, has elevated the importance of biliary stenting. This review aimed to systematically evaluate recent advancements in biliary stent materials and coatings, assessing their role in treating biliary stenosis and obstruction, with an emphasis on multifunctional coatings to enhance stent safety, efficacy, and patient outcomes while minimizing complications. Antimicrobial coatings, such as those with silver ions or chitosan, reduce infection risk; drug-eluting coatings, incorporating antibiotics or paclitaxel, mitigate infection and tumor progression; antiadhesion coatings extend stent patency. Furthermore, 3D printing enables patient-specific stent designs for optimal fit, while smart stents with integrated sensors enhance therapeutic precision by monitoring biliary parameters in real time. Multifunctional coatings and advanced materials substantially improve biliary stent performance, offering safer and more effective treatment options for biliary diseases. This review synthesizes the advantages and challenges of current technologies and recommends that future research should prioritize smart stents, biodegradable materials, and multifunctional coatings, validating their long-term safety and efficacy through clinical trials to optimize patient outcomes and advance clinical applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 11","pages":"9602–9633"},"PeriodicalIF":4.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145429662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Food packaging films containing biobased fillers can offer improved functional properties while meeting current environmental sustainability requirements for a circular and sustainable society. In this work, biocomposites based on chitin nanofibers and PVA have been developed in order to improve the mechanical performance and water barrier properties, performing for the first time a life cycle assessment. The biocolloids employed are chitin nanofibrils (ChNFs) from fungi, an underutilized renewable carbon feedstock in packaging, which are more environmentally friendly than conventional ChNFs obtained from crustaceans. Free-standing nanocomposite films are obtained by solvent casting, using water as the sole solvent. The incorporation of ChNFs results in a mechanical reinforcing effect of PVA that increases the Young modulus. The water vapor barrier character of PVA is significantly enhanced by the presence of ChNFs, which is decreased by 70% upon the incorporation of 10% ChNFs, overcoming one of the most significant drawbacks of PVA. The nanocomposites maintain an excellent oxygen barrier character under high relative humidity. Life cycle assessment (LCA) reveals a global warming potential of 5.0–5.2 kg·CO2 equiv·kg–1 for PVA/ChNFs films, demonstrating clear environmental benefits of the incorporation of ChNFs when considering the final properties. Overall, this work highlights the potential of fungal ChNFs to improve the mechanical properties and significantly improve the water barrier character of PVA, overcoming one of the limitations of this material in a sustainable way, as demonstrated by LCA.
{"title":"Fungal Chitin Nanofibrils to Improve the Functional Properties of Poly(vinyl alcohol) Films for Sustainable Food Packaging","authors":"Md Shafi Alam, , , Leire Sangroniz, , , Miriam Scoti, , , Alba Gonzalez, , , Agustin Etxeberria, , , Ainara Sangroniz*, , and , Erlantz Lizundia*, ","doi":"10.1021/acsabm.5c01723","DOIUrl":"10.1021/acsabm.5c01723","url":null,"abstract":"<p >Food packaging films containing biobased fillers can offer improved functional properties while meeting current environmental sustainability requirements for a circular and sustainable society. In this work, biocomposites based on chitin nanofibers and PVA have been developed in order to improve the mechanical performance and water barrier properties, performing for the first time a life cycle assessment. The biocolloids employed are chitin nanofibrils (ChNFs) from fungi, an underutilized renewable carbon feedstock in packaging, which are more environmentally friendly than conventional ChNFs obtained from crustaceans. Free-standing nanocomposite films are obtained by solvent casting, using water as the sole solvent. The incorporation of ChNFs results in a mechanical reinforcing effect of PVA that increases the Young modulus. The water vapor barrier character of PVA is significantly enhanced by the presence of ChNFs, which is decreased by 70% upon the incorporation of 10% ChNFs, overcoming one of the most significant drawbacks of PVA. The nanocomposites maintain an excellent oxygen barrier character under high relative humidity. Life cycle assessment (LCA) reveals a global warming potential of 5.0–5.2 kg·CO<sub>2</sub> equiv·kg<sup>–1</sup> for PVA/ChNFs films, demonstrating clear environmental benefits of the incorporation of ChNFs when considering the final properties. Overall, this work highlights the potential of fungal ChNFs to improve the mechanical properties and significantly improve the water barrier character of PVA, overcoming one of the limitations of this material in a sustainable way, as demonstrated by LCA.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 11","pages":"10381–10392"},"PeriodicalIF":4.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145429686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cisplatin (CDDP), a widely used chemotherapeutic agent, is limited by severe ototoxicity side effects. Local drug delivery via the middle ear represents the most effective approach for treating inner ear disease. However, therapeutic efficacy is constrained by poor middle ear retention and limited permeability across the round window membrane (RWM). Quercetin (QU) exhibits potent activity against CDDP-induced cytotoxicity but suffers from delivery challenges. To address this, we developed amino-functionalized mesoporous silica nanoparticles (NH2-MSNs) loaded with QU (QU-N-MSNs), leveraging the permselective properties of the RWM. This system was noninvasively administered to the cochlea via trans-tympanic delivery. The synthesized QU-N-MSNs demonstrated a uniform particle size of approximately 116–124 nm, positive charge, and sustained drug release properties. Compared to free QU, QU-N-MSNs demonstrated significantly enhanced antiapoptotic and cytoprotective activities in vitro. In vivo studies confirmed nanoparticle retention within the inner ear for ≥14 days post administration and efficient RWM penetration. Pretreatment with QU-N-MSNs prior to CDDP exposure in murine models substantially mitigated ototoxicity, as evidenced by reduced hearing threshold shifts across multiple frequencies, preservation of hair cells (HCs) and spiral ganglion neurons (SGNs), and attenuation of mitochondrial-mediated SGN apoptosis. These findings establish QU-N-MSNs as an effective RWM-penetrating delivery platform, offering a promising strategy to enhance hydrophobic drug bioavailability in the inner ear and prevent CDDP-induced ototoxicity.
顺铂(CDDP)是一种广泛使用的化疗药物,但其严重的耳毒性副作用限制了顺铂的应用。经中耳局部给药是治疗内耳疾病最有效的方法。然而,治疗效果受到中耳潴留不良和圆窗膜(RWM)渗透性有限的限制。槲皮素(QU)对cddp诱导的细胞毒性表现出有效的活性,但存在递送困难。为了解决这个问题,我们开发了氨基功能化的介孔二氧化硅纳米颗粒(NH2-MSNs),负载QU (QU- n - msns),利用RWM的超选择性。该系统通过跨鼓室输送无创给药到耳蜗。所合成的QU-N-MSNs具有均匀的粒径,约为116-124 nm,带正电荷,具有持续释放药物的特性。与游离QU相比,QU- n - msns在体外表现出明显增强的抗凋亡和细胞保护活性。体内研究证实纳米颗粒在给药后内耳内保留≥14天,RWM有效渗透。在小鼠模型中,在CDDP暴露之前,用q - n - msns进行预处理可以显著减轻耳毒性,这可以通过降低多个频率的听阈偏移、保存毛细胞(hc)和螺旋神经节神经元(SGN)以及减少线粒体介导的SGN凋亡来证明。这些研究结果表明,QU-N-MSNs是一种有效的穿透rwm的递送平台,为提高疏水药物在内耳的生物利用度和预防cddp诱导的耳毒性提供了一种有希望的策略。
{"title":"Mesoporous Silica Nanoparticles for Quercetin-Controlled Delivery to Protect Cisplatin-Induced Ototoxicity","authors":"Muyao Shen, , , Handong Wang, , , Junfeng Liu, , , Zixin Zhou, , , Xingguang Wu, , , Hanqi Fan, , , Haoliang Du, , , Yue Qiu, , , Dingding Liu, , , Dengbin Ma, , , Yong Wang, , , Zhao Tang, , , Shu Yang, , , Yuan Zhang*, , , Tianhong Zhang*, , and , Xia Gao*, ","doi":"10.1021/acsabm.5c01746","DOIUrl":"10.1021/acsabm.5c01746","url":null,"abstract":"<p >Cisplatin (CDDP), a widely used chemotherapeutic agent, is limited by severe ototoxicity side effects. Local drug delivery via the middle ear represents the most effective approach for treating inner ear disease. However, therapeutic efficacy is constrained by poor middle ear retention and limited permeability across the round window membrane (RWM). Quercetin (QU) exhibits potent activity against CDDP-induced cytotoxicity but suffers from delivery challenges. To address this, we developed amino-functionalized mesoporous silica nanoparticles (NH<sub>2</sub>-MSNs) loaded with QU (QU-N-MSNs), leveraging the permselective properties of the RWM. This system was noninvasively administered to the cochlea via trans-tympanic delivery. The synthesized QU-N-MSNs demonstrated a uniform particle size of approximately 116–124 nm, positive charge, and sustained drug release properties. Compared to free QU, QU-N-MSNs demonstrated significantly enhanced antiapoptotic and cytoprotective activities in vitro. In vivo studies confirmed nanoparticle retention within the inner ear for ≥14 days post administration and efficient RWM penetration. Pretreatment with QU-N-MSNs prior to CDDP exposure in murine models substantially mitigated ototoxicity, as evidenced by reduced hearing threshold shifts across multiple frequencies, preservation of hair cells (HCs) and spiral ganglion neurons (SGNs), and attenuation of mitochondrial-mediated SGN apoptosis. These findings establish QU-N-MSNs as an effective RWM-penetrating delivery platform, offering a promising strategy to enhance hydrophobic drug bioavailability in the inner ear and prevent CDDP-induced ototoxicity.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 11","pages":"10419–10435"},"PeriodicalIF":4.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsabm.5c01746","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hema Bhardwaj*, , , G.B.V.S. Lakshmi, , and , Pratima R. Solanki*,
The present work focuses on the development of a disposable electrochemical biosensor for simultaneous dual cancer biomarker detection onto a single-sensing platform. For this, an indigenously designed four-electrode system having two working areas of electrodes on a single screen-printed electrode (SPE) substrate was coated by graphite-based conductive ink. The first working electrode surface decorated by the prepared complex is composed of chitosan-functionalized 1T phase of tungsten disulfide-gold nanoparticles (f-WS2@AuNPs) composite and activated antibodies of tagged Cancer Antigen 125 (ab-tg-CA-125), while the second working electrode contained f-WS2@AuNPs and antibody of Human Epididymis protein 4 (ab-HE4). Further, both working electrodes were passivated by BSA to block nonspecific signals. Dual antibody-immobilized platforms of ab-tg-CA-125/f-WS2@AuNPs/SPE and ab-HE4/f-WS2@AuNPs/SPE were further used for simultaneous detection of two ovarian cancer biomarkers of CA-125 and HE4 using an electrochemical differential pulse voltammetry (DPV) technique. Fabricated electrochemical immunosensing platforms of ab-tg-CA-125/f-WS2@AuNPs/SPE and ab-HE4/f-WS2@AuNPs/SPE worked in the range of 0.001–25 μg mL–1 for CA-125 detection and 0.001–10 ng mL–1 for HE4 detection. The developed immunosensor showed a limit of detection of 0.001 μg mL–1 for CA-125 and 0.001 ng mL–1 for HE4. Also, the sensitivity of the developed electrochemical biosensor was calculated for CA-125 and HE4 and found to be 1.43 μA(log μg mL–1)−1 cm–2 and 1.092 μA(log ng mL–1)−1 cm–2, respectively. Both ab-CA-125 and ab-HE4 antibodies exhibit a larger value of association constant (Ka) and reveals strong binding affinity of antibodies toward respective cancer biomarkers. Moreover, the developed biosensors were tested with clinical ovarian patient serum samples, and the results were compared with the immunoassay kit. Therefore, these findings show the effective biosensor performance in terms of sensitivity, selectivity, accuracy, and faster response for simultaneous ovarian biomarker detection in clinical samples.
目前的工作重点是开发一种一次性电化学生物传感器,用于在单一传感平台上同时检测双重癌症生物标志物。为此,一种自主设计的四电极系统在单个丝网印刷电极(SPE)衬底上具有两个电极工作区域,并用石墨基导电油墨涂覆。所制备的配合物修饰的第一工作电极表面由壳聚糖功能化的二硫化钨-金纳米颗粒1T相(f-WS2@AuNPs)复合物和标记癌抗原125 (ab-tg-CA-125)的活化抗体组成,而第二工作电极表面含有f-WS2@AuNPs和人附睾蛋白4 (ab-HE4)的抗体。此外,两个工作电极都被BSA钝化以阻断非特异性信号。采用电化学差分脉冲伏安法(DPV)同时检测CA-125和HE4两种卵巢癌生物标志物:ab-tg-CA-125/f-WS2@AuNPs/SPE和ab-HE4/f-WS2@AuNPs/SPE双抗体固定化平台。制备的ab-tg-CA-125/f-WS2@AuNPs/SPE和ab-HE4/f-WS2@AuNPs/SPE电化学免疫传感平台的CA-125检测范围为0.001 ~ 25 μg mL-1, HE4检测范围为0.001 ~ 10 ng mL-1。该免疫传感器CA-125的检测限为0.001 μg mL-1, HE4的检测限为0.001 ng mL-1。计算了电化学生物传感器对CA-125和HE4的灵敏度,分别为1.43 μA(log μg mL-1)-1 cm-2和1.092 μA(log ng mL-1)-1 cm-2。ab-CA-125和ab-HE4抗体均表现出较大的关联常数(Ka)值,表明抗体对各自的癌症生物标志物具有较强的结合亲和力。将所研制的生物传感器与临床卵巢患者血清样本进行检测,并与免疫测定试剂盒进行比较。因此,这些研究结果表明,在临床样品中同时检测卵巢生物标志物方面,生物传感器在灵敏度、选择性、准确性和更快的响应方面具有有效的性能。
{"title":"Smartphone-Enabled Electrochemical Biosensor for Simultaneous Detection of Cancer Biomarkers Using f-WS2@AuNPs Screen-Printed Electrodes","authors":"Hema Bhardwaj*, , , G.B.V.S. Lakshmi, , and , Pratima R. Solanki*, ","doi":"10.1021/acsabm.5c01571","DOIUrl":"10.1021/acsabm.5c01571","url":null,"abstract":"<p >The present work focuses on the development of a disposable electrochemical biosensor for simultaneous dual cancer biomarker detection onto a single-sensing platform. For this, an indigenously designed four-electrode system having two working areas of electrodes on a single screen-printed electrode (SPE) substrate was coated by graphite-based conductive ink. The first working electrode surface decorated by the prepared complex is composed of chitosan-functionalized 1T phase of tungsten disulfide-gold nanoparticles (f-WS<sub>2</sub>@AuNPs) composite and activated antibodies of tagged Cancer Antigen 125 (ab-tg-CA-125), while the second working electrode contained f-WS<sub>2</sub>@AuNPs and antibody of Human Epididymis protein 4 (ab-HE4). Further, both working electrodes were passivated by BSA to block nonspecific signals. Dual antibody-immobilized platforms of ab-tg-CA-125/f-WS<sub>2</sub>@AuNPs/SPE and ab-HE4/f-WS<sub>2</sub>@AuNPs/SPE were further used for simultaneous detection of two ovarian cancer biomarkers of CA-125 and HE4 using an electrochemical differential pulse voltammetry (DPV) technique. Fabricated electrochemical immunosensing platforms of ab-tg-CA-125/f-WS<sub>2</sub>@AuNPs/SPE and ab-HE4/f-WS<sub>2</sub>@AuNPs/SPE worked in the range of 0.001–25 μg mL<sup>–1</sup> for CA-125 detection and 0.001–10 ng mL<sup>–1</sup> for HE4 detection. The developed immunosensor showed a limit of detection of 0.001 μg mL<sup>–1</sup> for CA-125 and 0.001 ng mL<sup>–1</sup> for HE4. Also, the sensitivity of the developed electrochemical biosensor was calculated for CA-125 and HE4 and found to be 1.43 μA(log μg mL<sup>–1</sup>)<sup>−1</sup> cm<sup>–2</sup> and 1.092 μA(log ng mL<sup>–1</sup>)<sup>−1</sup> cm<sup>–2</sup>, respectively. Both ab-CA-125 and ab-HE4 antibodies exhibit a larger value of association constant (<i>K</i><sub>a</sub>) and reveals strong binding affinity of antibodies toward respective cancer biomarkers. Moreover, the developed biosensors were tested with clinical ovarian patient serum samples, and the results were compared with the immunoassay kit. Therefore, these findings show the effective biosensor performance in terms of sensitivity, selectivity, accuracy, and faster response for simultaneous ovarian biomarker detection in clinical samples.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 11","pages":"10311–10324"},"PeriodicalIF":4.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natural sodium alginate hydrogels have low active ingredient release rates and significant volumetric shrinkage. Usually, a stable skeletal structure needs to be introduced to maintain the stability of the gel. In this study, four types of environmentally friendly nanocellulose (prepared via mechanical, enzymatic, acid hydrolysis, and oxidation methods) were incorporated into sodium alginate matrices to modify the gel network structure. Leveraging the gelation mechanism of sodium alginate and the regulatory influence of nanocellulose, a calcium ion-nanocellulose interpenetrating network was established at the microscopic level. The compatibility and reinforcement effects of different nanocellulose types were compared systematically, discovering that when the addition of micronano cellulose MCNF, obtained through ultrafine grinding, was 0.8%, the gel mask achieved an antishrinking rate of over 50%, an encapsulation efficiency of 56.73%, a release rate of 45.90% at 15 min, and an effective release rate of 26.04%, laying the foundation for further expansion of the application of mmicronano cellulose and SA.
{"title":"Comparative Network Design of Nanocellulose–Alginate Hydrogels with Enhanced Release and Shrinkage Resistance","authors":"Jinsong Zeng, , , Yuan Peng, , , Pengfei Li*, , , Chen Wu*, , , Jinpeng Li, , , Bin Wang, , , Jun Xu, , , Wenhua Gao, , , Daxian Cao, , and , Kefu Chen, ","doi":"10.1021/acsabm.5c01117","DOIUrl":"10.1021/acsabm.5c01117","url":null,"abstract":"<p >Natural sodium alginate hydrogels have low active ingredient release rates and significant volumetric shrinkage. Usually, a stable skeletal structure needs to be introduced to maintain the stability of the gel. In this study, four types of environmentally friendly nanocellulose (prepared via mechanical, enzymatic, acid hydrolysis, and oxidation methods) were incorporated into sodium alginate matrices to modify the gel network structure. Leveraging the gelation mechanism of sodium alginate and the regulatory influence of nanocellulose, a calcium ion-nanocellulose interpenetrating network was established at the microscopic level. The compatibility and reinforcement effects of different nanocellulose types were compared systematically, discovering that when the addition of micronano cellulose MCNF, obtained through ultrafine grinding, was 0.8%, the gel mask achieved an antishrinking rate of over 50%, an encapsulation efficiency of 56.73%, a release rate of 45.90% at 15 min, and an effective release rate of 26.04%, laying the foundation for further expansion of the application of mmicronano cellulose and SA.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 11","pages":"9824–9839"},"PeriodicalIF":4.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}