Naiyue Zhang, Liwen Jiang, Yumeng Yue, Xiaomin Zhao, Yanwei Hu, Yali Shi, Liying Zhao and Dawei Deng
The urgent need to curb the rampant rise in cancer has impelled the rapid development of nanomedicine. Under the above issue, transition metal compounds have received special attention considering their physicochemical and biochemical properties. However, how to take full advantage of the valuable characteristics of nanomaterials based on their spatial structures and chemical components for synergistic tumor therapy is a worthwhile exploration. In this work, a tailored two-dimensional (2D) FeSe2 nanosheet (NS) platform is proposed, which integrates enzyme activity and drug efficacy through the regulation of itsstability. Specifically, metastable FeSe2 NSs can serve as dual nanozymes in an intact state, depleting GSH and increasing ROS to induce oxidative stress in the tumor microenvironment (TME). With the gradual degradation of the FeSe2 in TME, its degraded products can amplify the Fenton reaction and GSH consumption, enhance the expression of inflammatory factors, and achieve effective near-infrared (NIR)-light irradiation-enhanced synergistic photothermal therapy (PTT) and chemodynamic therapy (CDT). Our exploration further confirmed such a strategy that may integrate carrier activity and drug action into a metastable nanoplatform for tumor synergistic therapy. These results prompt the consideration of the rational design of a one-for-all carrier that can exhibit multifunctional properties and nanomedicine efficacy for versatile therapeutic applications in the future.
{"title":"Metastable FeSe2 nanosheets as a one-for-all platform for stepwise synergistic tumor therapy†","authors":"Naiyue Zhang, Liwen Jiang, Yumeng Yue, Xiaomin Zhao, Yanwei Hu, Yali Shi, Liying Zhao and Dawei Deng","doi":"10.1039/D4TB00825A","DOIUrl":"10.1039/D4TB00825A","url":null,"abstract":"<p >The urgent need to curb the rampant rise in cancer has impelled the rapid development of nanomedicine. Under the above issue, transition metal compounds have received special attention considering their physicochemical and biochemical properties. However, how to take full advantage of the valuable characteristics of nanomaterials based on their spatial structures and chemical components for synergistic tumor therapy is a worthwhile exploration. In this work, a tailored two-dimensional (2D) FeSe<small><sub>2</sub></small> nanosheet (NS) platform is proposed, which integrates enzyme activity and drug efficacy through the regulation of itsstability. Specifically, metastable FeSe<small><sub>2</sub></small> NSs can serve as dual nanozymes in an intact state, depleting GSH and increasing ROS to induce oxidative stress in the tumor microenvironment (TME). With the gradual degradation of the FeSe<small><sub>2</sub></small> in TME, its degraded products can amplify the Fenton reaction and GSH consumption, enhance the expression of inflammatory factors, and achieve effective near-infrared (NIR)-light irradiation-enhanced synergistic photothermal therapy (PTT) and chemodynamic therapy (CDT). Our exploration further confirmed such a strategy that may integrate carrier activity and drug action into a metastable nanoplatform for tumor synergistic therapy. These results prompt the consideration of the rational design of a one-for-all carrier that can exhibit multifunctional properties and nanomedicine efficacy for versatile therapeutic applications in the future.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingzhu Shi, Sharat Chandra Barman, Shibo Cheng and Yong Zeng
The enzyme-linked immunosorbent assay (ELISA) remains the prevailing method for quantifying protein biomarkers. Enzymatic signal generation and amplification are key mechanisms that govern its analytical performance. This study reports the synthesis and application of microscale metal–organic framework (MOF)/enzyme composite particles as a novel detection probe to substantially enhance the sensitivity of ELISA. An optimal one-pot approach was established to incorporate a substantial amount of streptavidin-horseradish peroxidase (SA-HRP) either within or on the surface of the metal-azolate framework (MAF-7) microparticles. This approach enables the labeling of a single sandwich antibody–antigen complex with numerous enzymes, which markedly amplifies the enzymatic colorimetric signal generation. Moreover, MAF-7 caging was found to enhance the reactivity of the caged HRP enzyme, further promoting the overall detection sensitivity of ELISA. Compared to other developments that are often associated with more complicated detection modalities, our method is compatible with standard immunoassays and commonly used photometrical signal detection. The implementation of this strategy in the detection of CD147 results in a remarkably low limit of detection of 2.8 fg mL−1, representing a 105-fold improvement compared to that obtained with the standard ELISA. Moreover, the heightened sensitivity of this technique renders it particularly suitable for diagnosing breast cancer, thus presenting a promising tool for the early detection of the disease in clinical settings.
{"title":"Metal–organic framework-interfaced ELISA probe enables ultrasensitive detection of extracellular vesicle biomarkers†","authors":"Jingzhu Shi, Sharat Chandra Barman, Shibo Cheng and Yong Zeng","doi":"10.1039/D4TB00585F","DOIUrl":"10.1039/D4TB00585F","url":null,"abstract":"<p >The enzyme-linked immunosorbent assay (ELISA) remains the prevailing method for quantifying protein biomarkers. Enzymatic signal generation and amplification are key mechanisms that govern its analytical performance. This study reports the synthesis and application of microscale metal–organic framework (MOF)/enzyme composite particles as a novel detection probe to substantially enhance the sensitivity of ELISA. An optimal one-pot approach was established to incorporate a substantial amount of streptavidin-horseradish peroxidase (SA-HRP) either within or on the surface of the metal-azolate framework (MAF-7) microparticles. This approach enables the labeling of a single sandwich antibody–antigen complex with numerous enzymes, which markedly amplifies the enzymatic colorimetric signal generation. Moreover, MAF-7 caging was found to enhance the reactivity of the caged HRP enzyme, further promoting the overall detection sensitivity of ELISA. Compared to other developments that are often associated with more complicated detection modalities, our method is compatible with standard immunoassays and commonly used photometrical signal detection. The implementation of this strategy in the detection of CD147 results in a remarkably low limit of detection of 2.8 fg mL<small><sup>−1</sup></small>, representing a 10<small><sup>5</sup></small>-fold improvement compared to that obtained with the standard ELISA. Moreover, the heightened sensitivity of this technique renders it particularly suitable for diagnosing breast cancer, thus presenting a promising tool for the early detection of the disease in clinical settings.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteoarthritis (OA) is a prevalent chronic health condition necessitating effective treatment strategies. Globally, there were 86 million people with incident knee osteoarthritis in 2020. Pain management remains the primary approach to OA as the nature of cartilage poses challenges for drug delivery. An emulsion-based delivery system, using a class of positively charged and hydrolysable polymers (poly-beta-amino-esters) to coat oil droplets containing drugs, has been shown to enhance and prolong drug localization in ex vivo cartilage models. As the properties of the polymers used in this technology strongly depend on the monomers used in the synthesis, this study presents the screening of a wide range of PBAEs as droplet coating agents and using ketorolac as a model of nonsteroidal anti-inflammatory drugs. The emulsions prepared with this PBAE library were characterized, and drug localisation and retention were evaluated in both native and glycosaminoglycan (GAG) depleted cartilage ex vivo models. Optimal candidates were identified and tested in an ex vivo model showing the ability to protect chondrocyte cell viability and increase both GAG and collagen contents in cartilage exposed to cytokine (IL-1α) simulating acute cartilage damage. This work demonstrates the potential of PBAE coated emulsion as a delivery system for effective drug delivery in OA treatment.
骨关节炎(OA)是一种普遍存在的慢性疾病,需要采取有效的治疗策略。到 2020 年,全球将有 8600 万膝关节骨关节炎患者。由于软骨的性质给给药带来了挑战,疼痛治疗仍然是治疗 OA 的主要方法。一种基于乳液的给药系统,使用一类带正电荷且可水解的聚合物(聚-β-氨基酯)包裹含有药物的油滴,已被证明可在体外软骨模型中增强和延长药物定位。由于该技术中使用的聚合物的特性在很大程度上取决于合成中使用的单体,因此本研究以酮咯酸为非甾体抗炎药物模型,筛选了多种 PBAEs 作为液滴包衣剂。研究人员对使用该 PBAE 库制备的乳液进行了表征,并在原生软骨和去糖胺聚糖 (GAG) 软骨体外模型中对药物的定位和保留进行了评估。确定了最佳候选药物,并在体外模型中进行了测试,结果表明,在暴露于模拟急性软骨损伤的细胞因子(IL-1α)的软骨中,这些候选药物能够保护软骨细胞的活力,并增加软骨中 GAG 和胶原蛋白的含量。这项工作证明了 PBAE 涂层乳液作为一种给药系统在治疗 OA 方面的潜力。
{"title":"Screening of poly-beta amino ester coated emulsion of ketorolac for cartilage delivery†","authors":"Tahani Saeedi and Polina Prokopovich","doi":"10.1039/D4TB00313F","DOIUrl":"10.1039/D4TB00313F","url":null,"abstract":"<p >Osteoarthritis (OA) is a prevalent chronic health condition necessitating effective treatment strategies. Globally, there were 86 million people with incident knee osteoarthritis in 2020. Pain management remains the primary approach to OA as the nature of cartilage poses challenges for drug delivery. An emulsion-based delivery system, using a class of positively charged and hydrolysable polymers (poly-beta-amino-esters) to coat oil droplets containing drugs, has been shown to enhance and prolong drug localization in <em>ex vivo</em> cartilage models. As the properties of the polymers used in this technology strongly depend on the monomers used in the synthesis, this study presents the screening of a wide range of PBAEs as droplet coating agents and using ketorolac as a model of nonsteroidal anti-inflammatory drugs. The emulsions prepared with this PBAE library were characterized, and drug localisation and retention were evaluated in both native and glycosaminoglycan (GAG) depleted cartilage <em>ex vivo</em> models. Optimal candidates were identified and tested in an <em>ex vivo</em> model showing the ability to protect chondrocyte cell viability and increase both GAG and collagen contents in cartilage exposed to cytokine (IL-1α) simulating acute cartilage damage. This work demonstrates the potential of PBAE coated emulsion as a delivery system for effective drug delivery in OA treatment.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/tb/d4tb00313f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesca Laneri, Cristina Parisi, Mimimorena Seggio, Aurore Fraix, Giuseppe Longobardi, Ovidio Catanzano, Fabiana Quaglia and Salvatore Sortino
The strict dependence of the biological effects of nitric oxide (NO) on its concentration and generation site requires this inorganic free radical to be delivered with precise spatiotemporal control. Light-activation by suitable NO photoprecursors represents an ideal approach. Developing strategies to activate NO release using long-wavelength excitation light in the therapeutic window (650–1300 nm) is challenging. In this contribution, we demonstrate that NO release by a blue-light activatable NO photodonor (NOPD) with self-fluorescence reporting can be triggered catalytically by the much more biocompatible red light exploiting a supramolecular photosensitization process. Different red-light absorbing photosensitizers (PSs) are co-entrapped with the NOPD within different biocompatible nanocarriers such as Pluronic® micelles, microemulsions and branched cyclodextrin polymers. The intra-carrier photosensitized NO release, involving the lowest, long-lived triplet state of the PS as the key intermediate and its quenching by the NOPD, is competitive with that by molecular oxygen. This allows NO to be released with good efficacy, even under aerobic conditions. Therefore, the adopted general strategy provides a valuable tool for generating NO from an already available NOPD, otherwise activatable with the poorly biocompatible blue light, without requiring any chemical modification and using sophisticated and expensive irradiation sources.
一氧化氮(NO)的生物效应与其浓度和生成部位密切相关,这就要求对这种无机自由基的传递进行精确的时空控制。用合适的一氧化氮光前驱体进行光激活是一种理想的方法。利用治疗窗口(650-1300 纳米)内的长波长激发光来激活 NO 释放的策略开发具有挑战性。在这篇论文中,我们证明了具有自发荧光报告功能的蓝光可激活 NO 光引发剂(NOPD)可利用超分子光敏化过程,通过生物相容性更好的红光催化 NO 释放。不同的红光吸收光敏剂(PSs)与 NOPD 共同包裹在不同的生物相容性纳米载体(如 Pluronic® 胶束、微乳液和支链环糊精聚合物)中。载体内光敏 NO 的释放涉及作为关键中间体的 PS 的最低长寿命三重态以及 NOPD 对其的淬灭,与分子氧的释放具有竞争性。因此,即使在有氧条件下,NO 的释放效果也很好。因此,所采用的一般策略为利用已有的 NOPD 生成氮氧化物提供了一种宝贵的工具,这种 NOPD 可通过生物相容性较差的蓝光激活,而无需进行任何化学修饰,也无需使用复杂而昂贵的辐照源。
{"title":"Supramolecular red-light-photosensitized nitric oxide release with fluorescence self-reporting within biocompatible nanocarriers","authors":"Francesca Laneri, Cristina Parisi, Mimimorena Seggio, Aurore Fraix, Giuseppe Longobardi, Ovidio Catanzano, Fabiana Quaglia and Salvatore Sortino","doi":"10.1039/D4TB00325J","DOIUrl":"10.1039/D4TB00325J","url":null,"abstract":"<p >The strict dependence of the biological effects of nitric oxide (NO) on its concentration and generation site requires this inorganic free radical to be delivered with precise spatiotemporal control. Light-activation by suitable NO photoprecursors represents an ideal approach. Developing strategies to activate NO release using long-wavelength excitation light in the therapeutic window (650–1300 nm) is challenging. In this contribution, we demonstrate that NO release by a blue-light activatable NO photodonor (NOPD) with self-fluorescence reporting can be triggered catalytically by the much more biocompatible red light exploiting a supramolecular photosensitization process. Different red-light absorbing photosensitizers (PSs) are co-entrapped with the NOPD within different biocompatible nanocarriers such as Pluronic® micelles, microemulsions and branched cyclodextrin polymers. The intra-carrier photosensitized NO release, involving the lowest, long-lived triplet state of the PS as the key intermediate and its quenching by the NOPD, is competitive with that by molecular oxygen. This allows NO to be released with good efficacy, even under aerobic conditions. Therefore, the adopted general strategy provides a valuable tool for generating NO from an already available NOPD, otherwise activatable with the poorly biocompatible blue light, without requiring any chemical modification and using sophisticated and expensive irradiation sources.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/tb/d4tb00325j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Traumatic injuries, neurodegenerative diseases and oxidative stress serve as the early biomarkers for neuronal damage and impede angiogenesis and subsequently neuronal growth. Considering this, the present work aimed to develop a poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloylglutamate) hydrogel [p(NAG-Ac-NAE)] with angiogenesis/neurogenesis properties. As constituents of this polymer modulate their vital role in biological functions, inhibitory neurotransmitter glycine regulates neuronal homeostasis, and glutamatergic signalling regulates angiogenesis. The p(NAG-Ac-NAE) hydrogel is a highly branched, biodegradable and pH-responsive polymer with a very high swelling behavior of 6188%. The mechanical stability (G′, 2.3–2.7 kPa) of this polymeric hydrogel is commendable in the differentiation of mature neurons. This hydrogel is biocompatible (as tested in HUVEC cells) and helps to proliferate PC12 cells (152.7 ± 13.7%), whereas it is cytotoxic towards aggressive cancers such as glioblastoma (LN229 cells) and triple negative breast cancer (TNBC; MDA-MB-231 cells) and helps to maintain the healthy cytoskeleton framework structure of primary cortical neurons by facilitating the elongation of the axonal pathway. Furthermore, FACS results revealed that the synthesized hydrogel potentiates neurogenesis by inducing the cell cycle (G0/G1) and arresting the sub-G1 phase by limiting apoptosis. Additionally, RT-PCR results revealed that this hydrogel induced an increased level of HIF-1α expression, providing preconditioning effects towards neuronal cells under oxidative stress by scavenging ROS and initiating neurogenic and angiogenic signalling. This hydrogel further exhibits more pro-angiogenic activities by increasing the expression of VEGF isoforms compared to previously reported hydrogels. In conclusion, the newly synthesized p(NAG-Ac-NAE) hydrogel can be one of the potential neuroregenerative materials for vasculogenesis-assisted neurogenic applications and paramount for the management of neurodegenerative diseases.
{"title":"Neurogenic and angiogenic poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloyl-glutamate) hydrogel: preconditioning effect under oxidative stress and use in neuroregeneration†","authors":"Kirti Wasnik, Prem Shankar Gupta, Gurmeet Singh, Somedutta Maity, Sukanya Patra, Divya Pareek, Sandeep Kumar, Vipin Rai, Ravi Prakash, Arbind Acharya, Pralay Maiti, Sudip Mukherjee, Yitzhak Mastai and Pradip Paik","doi":"10.1039/D4TB00243A","DOIUrl":"10.1039/D4TB00243A","url":null,"abstract":"<p >Traumatic injuries, neurodegenerative diseases and oxidative stress serve as the early biomarkers for neuronal damage and impede angiogenesis and subsequently neuronal growth. Considering this, the present work aimed to develop a poly(<em>N</em>-acryloylglycine)-<em>co</em>-(acrylamide)-<em>co</em>-(<em>N</em>-acryloylglutamate) hydrogel [p(NAG-Ac-NAE)] with angiogenesis/neurogenesis properties. As constituents of this polymer modulate their vital role in biological functions, inhibitory neurotransmitter glycine regulates neuronal homeostasis, and glutamatergic signalling regulates angiogenesis. The p(NAG-Ac-NAE) hydrogel is a highly branched, biodegradable and pH-responsive polymer with a very high swelling behavior of 6188%. The mechanical stability (<em>G</em>′, 2.3–2.7 kPa) of this polymeric hydrogel is commendable in the differentiation of mature neurons. This hydrogel is biocompatible (as tested in HUVEC cells) and helps to proliferate PC12 cells (152.7 ± 13.7%), whereas it is cytotoxic towards aggressive cancers such as glioblastoma (LN229 cells) and triple negative breast cancer (TNBC; MDA-MB-231 cells) and helps to maintain the healthy cytoskeleton framework structure of primary cortical neurons by facilitating the elongation of the axonal pathway. Furthermore, FACS results revealed that the synthesized hydrogel potentiates neurogenesis by inducing the cell cycle (G0/G1) and arresting the sub-G1 phase by limiting apoptosis. Additionally, RT-PCR results revealed that this hydrogel induced an increased level of HIF-1α expression, providing preconditioning effects towards neuronal cells under oxidative stress by scavenging ROS and initiating neurogenic and angiogenic signalling. This hydrogel further exhibits more pro-angiogenic activities by increasing the expression of VEGF isoforms compared to previously reported hydrogels. In conclusion, the newly synthesized p(NAG-Ac-NAE) hydrogel can be one of the potential neuroregenerative materials for vasculogenesis-assisted neurogenic applications and paramount for the management of neurodegenerative diseases.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141249156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heewon Cho, Na-Kyeong Hong, Insung Yong, Haw-Young Kwon, Nam-Young Kang, Larissa Miasiro Ciaramicoli, Pilnam Kim and Young-Tae Chang
Advanced glycation end products (AGEs) play a pivotal role in the aging process, regarded as a hallmark of aging. Despite their significance, the absence of adequate monitoring tools has hindered the exploration of the relationship between AGEs and aging. Here, we present a novel AGE-selective probe, AGO, for the first time. AGO exhibited superior sensitivity in detecting AGEs compared to the conventional method of measuring autofluorescence from AGEs. Furthermore, we validated AGO's ability to detect AGEs based on kinetics, demonstrating a preference for ribose-derived AGEs. Lastly, AGO effectively visualized glycation products in a collagen-based mimicking model of glycation. We anticipate that this study will enhance the molecular tool sets available for comprehending the physiological processes of AGEs during aging.
高级糖化终产物(AGEs)在衰老过程中起着举足轻重的作用,被认为是衰老的标志。尽管其意义重大,但由于缺乏适当的监测工具,阻碍了对 AGEs 与衰老之间关系的探索。在这里,我们首次提出了一种新型 AGE 选择性探针 AGO。与测量 AGEs 自发荧光的传统方法相比,AGO 在检测 AGEs 方面表现出更高的灵敏度。此外,我们还根据动力学验证了 AGO 检测 AGE 的能力,证明了它对核糖衍生 AGE 的偏好。最后,在基于胶原蛋白的糖化模拟模型中,AGO 能有效地观察糖化产物。我们预计这项研究将增强现有的分子工具集,以了解 AGEs 在衰老过程中的生理过程。
{"title":"Development of a specific fluorescent probe to detect advanced glycation end products (AGEs)†","authors":"Heewon Cho, Na-Kyeong Hong, Insung Yong, Haw-Young Kwon, Nam-Young Kang, Larissa Miasiro Ciaramicoli, Pilnam Kim and Young-Tae Chang","doi":"10.1039/D4TB00590B","DOIUrl":"10.1039/D4TB00590B","url":null,"abstract":"<p >Advanced glycation end products (AGEs) play a pivotal role in the aging process, regarded as a hallmark of aging. Despite their significance, the absence of adequate monitoring tools has hindered the exploration of the relationship between AGEs and aging. Here, we present a novel AGE-selective probe, AGO, for the first time. AGO exhibited superior sensitivity in detecting AGEs compared to the conventional method of measuring autofluorescence from AGEs. Furthermore, we validated AGO's ability to detect AGEs based on kinetics, demonstrating a preference for ribose-derived AGEs. Lastly, AGO effectively visualized glycation products in a collagen-based mimicking model of glycation. We anticipate that this study will enhance the molecular tool sets available for comprehending the physiological processes of AGEs during aging.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/tb/d4tb00590b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developing synthetic materials, with enzyme-like molecular recognition capabilities, as functional receptors in electronic or electrochemical devices for the timely diagnosis of major diseases is a great challenge. Herein, we present the development of Fe/MIPpy nanozymes, characterized as enzyme-like artificial receptors, for the precise and non-invasive monitoring of cancer biomarkers in aqueous solutions and human saliva. Through the integration of PVA-stabilized FeFe2O4 nanocrystals in a molecularly imprinted conducting polypyrrole matrix, the Fe/MIPpy nanozymes demonstrate 424 nA cm−2 nM−1 sensitivity and 220 pM detection limit. Charge-transfer mechanisms, Fe/MIPpy–spermine interactions, and the principle of spermine recognition are investigated by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The disposable Fe/MIPpy sensor operates wirelessly and offers rapid and remote quantification of spermine, making it a promising material for the development of cost-effective tools for non-invasive cancer diagnosis and prognosis.
{"title":"Electrocatalytic FeFe2O4 embedded, spermine-imprinted polypyrrole (Fe/MIPpy) nanozymes for cancer diagnosis and prognosis†","authors":"Iqra Zaman, Amna Liaqat, Sadaf Athar, Adnan Mujahid and Adeel Afzal","doi":"10.1039/D4TB00190G","DOIUrl":"10.1039/D4TB00190G","url":null,"abstract":"<p >Developing synthetic materials, with enzyme-like molecular recognition capabilities, as functional receptors in electronic or electrochemical devices for the timely diagnosis of major diseases is a great challenge. Herein, we present the development of Fe/MIPpy nanozymes, characterized as enzyme-like artificial receptors, for the precise and non-invasive monitoring of cancer biomarkers in aqueous solutions and human saliva. Through the integration of PVA-stabilized FeFe<small><sub>2</sub></small>O<small><sub>4</sub></small> nanocrystals in a molecularly imprinted conducting polypyrrole matrix, the Fe/MIPpy nanozymes demonstrate 424 nA cm<small><sup>−2</sup></small> nM<small><sup>−1</sup></small> sensitivity and 220 pM detection limit. Charge-transfer mechanisms, Fe/MIPpy–spermine interactions, and the principle of spermine recognition are investigated by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The disposable Fe/MIPpy sensor operates wirelessly and offers rapid and remote quantification of spermine, making it a promising material for the development of cost-effective tools for non-invasive cancer diagnosis and prognosis.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dandan Ding, Shushan Mo, Qishan Li, Fei Wang, Xueyi Wang, Caiwen Ou and Zhenhua Li
Boron neutron capture therapy (BNCT) is an emerging approach for treating malignant tumors with binary targeting. However, its clinical application has been hampered by insufficient 10B accumulation in tumors and low 10B concentration ratios of tumor-to-blood (T/B) and tumor-to-normal tissue (T/N). Herein, we developed fluorinated BPA derivatives with different fluorine groups as boron delivery agents for enabling sufficient 10B accumulation in tumors and enhancing T/B and T/N ratios. Our findings demonstrated that fluorinated BPA derivatives had good biological safety. Furthermore, fluorinated BPA derivatives showed improved 10B accumulation in tumors and enhanced T/B and T/N ratios compared to the clinical boron drug fructose-BPA (f-BPA). In particular, in B16-F10 tumor-bearing mice, fluorinated BPA derivatives met the requirements for clinical BNCT even at half of the clinical dose. Thus, fluorinated BPA derivatives are potentially effective boron delivery agents for clinical BNCT in melanoma.
硼中子俘获疗法(BNCT)是一种新兴的二元靶向治疗恶性肿瘤的方法。然而,由于 10B 在肿瘤中积累不足,以及肿瘤与血液(T/B)和肿瘤与正常组织(T/N)的 10B 浓度比过低,其临床应用一直受到阻碍。在此,我们开发了具有不同氟基团的含氟双酚 A 衍生物作为硼传递剂,以实现 10B 在肿瘤中的充分积累,并提高 T/B 和 T/N 比值。我们的研究结果表明,含氟双酚 A 衍生物具有良好的生物安全性。此外,与临床硼药物果糖-双酚A(f-BPA)相比,氟化双酚A衍生物改善了10B在肿瘤中的积累,并提高了T/B和T/N比。特别是,在 B16-F10 肿瘤小鼠中,氟化双酚 A 衍生物甚至只需临床剂量的一半就能满足临床 BNCT 的要求。因此,氟化双酚A衍生物是用于黑色素瘤临床BNCT的潜在有效硼输送剂。
{"title":"Fluorinated BPA derivatives enhanced 10B delivery in tumors†","authors":"Dandan Ding, Shushan Mo, Qishan Li, Fei Wang, Xueyi Wang, Caiwen Ou and Zhenhua Li","doi":"10.1039/D4TB00846D","DOIUrl":"10.1039/D4TB00846D","url":null,"abstract":"<p >Boron neutron capture therapy (BNCT) is an emerging approach for treating malignant tumors with binary targeting. However, its clinical application has been hampered by insufficient <small><sup>10</sup></small>B accumulation in tumors and low <small><sup>10</sup></small>B concentration ratios of tumor-to-blood (T/B) and tumor-to-normal tissue (T/N). Herein, we developed fluorinated BPA derivatives with different fluorine groups as boron delivery agents for enabling sufficient <small><sup>10</sup></small>B accumulation in tumors and enhancing T/B and T/N ratios. Our findings demonstrated that fluorinated BPA derivatives had good biological safety. Furthermore, fluorinated BPA derivatives showed improved <small><sup>10</sup></small>B accumulation in tumors and enhanced T/B and T/N ratios compared to the clinical boron drug fructose-BPA (f-BPA). In particular, in B16-F10 tumor-bearing mice, fluorinated BPA derivatives met the requirements for clinical BNCT even at half of the clinical dose. Thus, fluorinated BPA derivatives are potentially effective boron delivery agents for clinical BNCT in melanoma.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141249155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhenhai Tang, Jianhua Zhang, Wenting Li, Kaiying Wen, Zhipeng Gu, Dongdong Zhou and Hao Su
Supramolecular polymers (SPs) are an emerging class of drug transporters employed to improve drug therapy. Through the rational design of self-assembling monomers, one can optimize the properties of the resulting supramolecular nanostructures, such as size, shape, surface chemistry, release, and, therefore, biological fates. This study highlights the design of isomeric SN38 prodrugs through the conjugation of hydrophilic oligo(ethylene glycol) (OEG) with hydroxyls at positions 10 and 20 on hydrophobic SN-38. Self-assembling prodrug (SAPD) isomers 10-OEG-SN38 and 20-OEG-SN38 can self-assemble into giant nanotubes and filamentous assemblies, respectively, via aromatic associations that dominate self-assembly. Our study reveales the influence of modification sites on the assembly behavior and ability of the SN38 SAPDs, as well as drug release and subsequent in vitro and in vivo antitumor effects. The SAPD modified at position 20 exhibits stronger π–π interactions among SN38 units, leading to more compact packing and enhanced assembly capability, whereas OEG at position 10 poses steric hindrance for aromatic associations. Importantly, owing to its higher chemical and supramolecular stability, 20-OEG-SN38 outperforms 10-OEG-SN38 and irinotecan, a clinically used prodrug of SN38, in a CT26 tumor model, demonstrating enhanced tumor growth inhibition and prolonged animal survival. This study presents a new strategy of using interactions among drug molecules as dominating features to create supramolecular assemblies. It also brings some insights into creating effective supramolecular drug assemblies via the engineering of self-assembling building blocks, which could contribute to the optimization of design principles for supramolecular drug delivery systems.
{"title":"Supramolecular assembly of isomeric SN-38 prodrugs regulated by conjugation sites†","authors":"Zhenhai Tang, Jianhua Zhang, Wenting Li, Kaiying Wen, Zhipeng Gu, Dongdong Zhou and Hao Su","doi":"10.1039/D4TB00717D","DOIUrl":"10.1039/D4TB00717D","url":null,"abstract":"<p >Supramolecular polymers (SPs) are an emerging class of drug transporters employed to improve drug therapy. Through the rational design of self-assembling monomers, one can optimize the properties of the resulting supramolecular nanostructures, such as size, shape, surface chemistry, release, and, therefore, biological fates. This study highlights the design of isomeric SN38 prodrugs through the conjugation of hydrophilic oligo(ethylene glycol) (OEG) with hydroxyls at positions 10 and 20 on hydrophobic SN-38. Self-assembling prodrug (SAPD) isomers 10-OEG-SN38 and 20-OEG-SN38 can self-assemble into giant nanotubes and filamentous assemblies, respectively, <em>via</em> aromatic associations that dominate self-assembly. Our study reveales the influence of modification sites on the assembly behavior and ability of the SN38 SAPDs, as well as drug release and subsequent <em>in vitro</em> and <em>in vivo</em> antitumor effects. The SAPD modified at position 20 exhibits stronger π–π interactions among SN38 units, leading to more compact packing and enhanced assembly capability, whereas OEG at position 10 poses steric hindrance for aromatic associations. Importantly, owing to its higher chemical and supramolecular stability, 20-OEG-SN38 outperforms 10-OEG-SN38 and irinotecan, a clinically used prodrug of SN38, in a CT26 tumor model, demonstrating enhanced tumor growth inhibition and prolonged animal survival. This study presents a new strategy of using interactions among drug molecules as dominating features to create supramolecular assemblies. It also brings some insights into creating effective supramolecular drug assemblies <em>via</em> the engineering of self-assembling building blocks, which could contribute to the optimization of design principles for supramolecular drug delivery systems.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mansoor Khan, Tanzil Ur Rahman, Luqman Ali Shah, Hazizan Md Akil, Jun Fu and Hyeong-Min Yoo
Metal organic frameworks (MOFs) have garnered significant attention in the development of stretchable and wearable conductive hydrogels for flexible transducers. However, MOFs used in hydrogel networks have been hampered by low mechanical performance and poor dispersibility in aqueous solutions, which affect the performance of hydrogels, including low toughness, limited self-recovery, short working ranges, low conductivity, and prolonged response–recovery times. To address these shortcomings, a novel approach was adopted in which micelle co-polymerization was used for the ex situ synthesis of Zn-MOF-based hydrogels with exceptional stretchability, robust toughness, anti-fatigue properties, and commendable conductivity. This breakthrough involved the ex situ integration of Zn-MOFs into hydrophobically cross-linked polymer chains. Here the micelles of EHDDAB had two functions, first they uniformly dispersed the Zn-MOFs and secondly they dynamically cross-linked the polymer chains, profoundly influencing the mechanical characteristics of the hydrogels. The non-covalent synergistic interactions introduced by Zn-MOFs endowed the hydrogels with the capacity for high stretchability, high stress, rapid self-recovery, anti-fatigue properties, and conductivity, all achieved without external stimuli. Furthermore, hydrogels based on Zn-MOFs can serve as durable and highly sensitive flexible transducers, adept at detecting diverse mechanical deformations with swift response–recovery times and high gauge factor values. Consequently, these hydrogels can be tailored to function as wearable strain sensors capable of sensing significant human joint movements, such as wrist bending, and motions involving the wrist, fingers, and elbows. Similarly, they excel at monitoring subtle human motions, such as speech pronunciation, distinguishing between different words, as well as detecting swallowing and larynx vibrations during various activities. Beyond these applications, the hydrogels exhibit proficiency in distinguishing and reproducing various written words with reliability. The Zn-MOF-based hydrogels hold promising potential for development in electronic skin, medical monitoring, soft robotics, and flexible touch panels.
{"title":"Multi-role conductive hydrogels for flexible transducers regulated by MOFs for monitoring human activities and electronic skin functions†","authors":"Mansoor Khan, Tanzil Ur Rahman, Luqman Ali Shah, Hazizan Md Akil, Jun Fu and Hyeong-Min Yoo","doi":"10.1039/D4TB00718B","DOIUrl":"10.1039/D4TB00718B","url":null,"abstract":"<p >Metal organic frameworks (MOFs) have garnered significant attention in the development of stretchable and wearable conductive hydrogels for flexible transducers. However, MOFs used in hydrogel networks have been hampered by low mechanical performance and poor dispersibility in aqueous solutions, which affect the performance of hydrogels, including low toughness, limited self-recovery, short working ranges, low conductivity, and prolonged response–recovery times. To address these shortcomings, a novel approach was adopted in which micelle co-polymerization was used for the <em>ex situ</em> synthesis of Zn-MOF-based hydrogels with exceptional stretchability, robust toughness, anti-fatigue properties, and commendable conductivity. This breakthrough involved the <em>ex situ</em> integration of Zn-MOFs into hydrophobically cross-linked polymer chains. Here the micelles of EHDDAB had two functions, first they uniformly dispersed the Zn-MOFs and secondly they dynamically cross-linked the polymer chains, profoundly influencing the mechanical characteristics of the hydrogels. The non-covalent synergistic interactions introduced by Zn-MOFs endowed the hydrogels with the capacity for high stretchability, high stress, rapid self-recovery, anti-fatigue properties, and conductivity, all achieved without external stimuli. Furthermore, hydrogels based on Zn-MOFs can serve as durable and highly sensitive flexible transducers, adept at detecting diverse mechanical deformations with swift response–recovery times and high gauge factor values. Consequently, these hydrogels can be tailored to function as wearable strain sensors capable of sensing significant human joint movements, such as wrist bending, and motions involving the wrist, fingers, and elbows. Similarly, they excel at monitoring subtle human motions, such as speech pronunciation, distinguishing between different words, as well as detecting swallowing and larynx vibrations during various activities. Beyond these applications, the hydrogels exhibit proficiency in distinguishing and reproducing various written words with reliability. The Zn-MOF-based hydrogels hold promising potential for development in electronic skin, medical monitoring, soft robotics, and flexible touch panels.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}