Fengqian Wang, Weicong Peng, Dongliang Huo, Jingxian Zhang, Suiping Deng, Langhuan Huang and Shaozao Tan
For decades, implant-associated infections (IAIs) caused by pathogenic bacteria have been associated with high failure and mortality rates in implantation surgeries, posing a serious threat to global public health. Therefore, developing a functionalized biomaterial coating with anti-fouling and anti-bacterial functions is crucial for alleviating implant infections. Herein, a near-infrared-responsive anti-bacterial and anti-adhesive coating (Ti-PEG-Cu2−xS) constructed on the surface of titanium (Ti) implants is reported. This coating is composed of nano-Cu2−xS with anti-bacterial activity and super-hydrophilic polyethylene glycol (PEG). Under near-infrared irradiation, the nano-catalyst Cu2−xS on the surface of Ti-PEG-Cu2−xS induces bacterial death by catalyzing the production of singlet oxygen (1O2). The Ti-PEG-Cu2−xS coating can effectively prevent bacterial adhesion and biofilm formation. This coating combines the antibacterial mechanisms of “active attack” and “passive defense”, which can kill bacteria and inhibit biofilm formation. The results of in vitro and in vivo experiments have shown that Ti-PEG-Cu2−xS exhibits excellent anti-bacterial properties under near-infrared irradiation and can effectively prevent implant-related infections caused by Escherichia coli (E. coli) ATCC 8739 and Staphylococcus aureus (S. aureus). The antibacterial efficiency of Ti-PEG-Cu2−xS coatings against E. coli was 99.96% ± 0.058% and that of S. aureus was 99.66% ± 0.26%, respectively. In addition, the Ti-PEG-Cu2−xS coating has good blood compatibility and excellent bactericidal ability. Therefore, this multifunctional coating combines a non-adhesive surface strategy and a near-infrared phototherapy sterilization method, effectively blocking the initial attachment and proliferation of bacteria on implants via photothermal/photodynamic effects and providing a promising method for preventing bacterium-induced IAIs.
{"title":"Cu2−xS homojunction coatings empower titanium implants with near-infrared-triggered antibacterial and antifouling properties†","authors":"Fengqian Wang, Weicong Peng, Dongliang Huo, Jingxian Zhang, Suiping Deng, Langhuan Huang and Shaozao Tan","doi":"10.1039/D4TB00235K","DOIUrl":"10.1039/D4TB00235K","url":null,"abstract":"<p >For decades, implant-associated infections (IAIs) caused by pathogenic bacteria have been associated with high failure and mortality rates in implantation surgeries, posing a serious threat to global public health. Therefore, developing a functionalized biomaterial coating with anti-fouling and anti-bacterial functions is crucial for alleviating implant infections. Herein, a near-infrared-responsive anti-bacterial and anti-adhesive coating (Ti-PEG-Cu<small><sub>2−<em>x</em></sub></small>S) constructed on the surface of titanium (Ti) implants is reported. This coating is composed of nano-Cu<small><sub>2−<em>x</em></sub></small>S with anti-bacterial activity and super-hydrophilic polyethylene glycol (PEG). Under near-infrared irradiation, the nano-catalyst Cu<small><sub>2−<em>x</em></sub></small>S on the surface of Ti-PEG-Cu<small><sub>2−<em>x</em></sub></small>S induces bacterial death by catalyzing the production of singlet oxygen (<small><sup>1</sup></small>O<small><sub>2</sub></small>). The Ti-PEG-Cu<small><sub>2−<em>x</em></sub></small>S coating can effectively prevent bacterial adhesion and biofilm formation. This coating combines the antibacterial mechanisms of “active attack” and “passive defense”, which can kill bacteria and inhibit biofilm formation. The results of <em>in vitro</em> and <em>in vivo</em> experiments have shown that Ti-PEG-Cu<small><sub>2−<em>x</em></sub></small>S exhibits excellent anti-bacterial properties under near-infrared irradiation and can effectively prevent implant-related infections caused by <em>Escherichia coli</em> (<em>E. coli</em>) ATCC 8739 and <em>Staphylococcus aureus</em> (<em>S. aureus</em>). The antibacterial efficiency of Ti-PEG-Cu<small><sub>2−<em>x</em></sub></small>S coatings against <em>E. coli</em> was 99.96% ± 0.058% and that of <em>S. aureus</em> was 99.66% ± 0.26%, respectively. In addition, the Ti-PEG-Cu<small><sub>2−<em>x</em></sub></small>S coating has good blood compatibility and excellent bactericidal ability. Therefore, this multifunctional coating combines a non-adhesive surface strategy and a near-infrared phototherapy sterilization method, effectively blocking the initial attachment and proliferation of bacteria on implants <em>via</em> photothermal/photodynamic effects and providing a promising method for preventing bacterium-induced IAIs.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159346","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}
Tissue damage and cell death occurring during photothermal therapy (PTT) for tumors can induce an inflammatory response that is detrimental to tumor therapy. Herein, ultrathin Mo metallene nanosheets with a thickness of <5 nm prepared by liquid phase exfoliation were explored as functional hyperthermia agents for non-inflammatory ablation of tumors. The obtained Mo metallene nanosheets exhibited good photothermal conversion properties and significant reactive oxygen species (ROS) scavenging ability, thus achieving superior cancer cell ablation and anti-inflammatory effects in vitro. For in vivo experiments, 4T1 tumors were ablated while the inflammation-related cytokine levels did not obviously increase, demonstrating that the inflammatory response induced by PTT was inhibited by the anti-inflammatory properties of Mo metallene nanosheets. Moreover, Mo metallene nanosheets depicted good dispersibility and biocompatibility, beneficial for biomedical applications. This work introduces Mo metallenes as promising hyperthermia agents for non-inflammatory PTT of tumors.
肿瘤光热疗法(PTT)过程中出现的组织损伤和细胞死亡会诱发炎症反应,从而不利于肿瘤治疗。在此,研究人员探索了用液相剥离法制备厚度小于 5 纳米的超薄钼金属纳米片作为功能性热疗剂,用于非炎症性消融肿瘤。所制备的钼金属纳米片具有良好的光热转换性能和显著的活性氧(ROS)清除能力,从而在体外实现了优异的癌细胞消融和抗炎效果。在体内实验中,4T1 肿瘤被消融的同时,与炎症相关的细胞因子水平并未明显升高,这表明金属钼纳米片的抗炎特性抑制了 PTT 诱导的炎症反应。此外,茂金属纳米片还具有良好的分散性和生物相容性,有利于生物医学应用。这项工作介绍了茂金属作为有望用于肿瘤非炎症性 PTT 的热疗剂。
{"title":"Liquid exfoliation of molybdenum metallenes for non-inflammatory photothermal therapy of tumors†","authors":"Chenxin Lu, Xiang Huang, Zhaoying Jin, Junwei Deng, Zhengbao Zha and Zhaohua Miao","doi":"10.1039/D4TB00525B","DOIUrl":"10.1039/D4TB00525B","url":null,"abstract":"<p >Tissue damage and cell death occurring during photothermal therapy (PTT) for tumors can induce an inflammatory response that is detrimental to tumor therapy. Herein, ultrathin Mo metallene nanosheets with a thickness of <5 nm prepared by liquid phase exfoliation were explored as functional hyperthermia agents for non-inflammatory ablation of tumors. The obtained Mo metallene nanosheets exhibited good photothermal conversion properties and significant reactive oxygen species (ROS) scavenging ability, thus achieving superior cancer cell ablation and anti-inflammatory effects <em>in vitro</em>. For <em>in vivo</em> experiments, 4T1 tumors were ablated while the inflammation-related cytokine levels did not obviously increase, demonstrating that the inflammatory response induced by PTT was inhibited by the anti-inflammatory properties of Mo metallene nanosheets. Moreover, Mo metallene nanosheets depicted good dispersibility and biocompatibility, beneficial for biomedical applications. This work introduces Mo metallenes as promising hyperthermia agents for non-inflammatory PTT of tumors.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140963114","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}
Yue Gao, Yeqi Huang, Chuanyu Ren, Peiwen Chou, Chuanbin Wu, Xin Pan, Guilan Quan and Zhengwei Huang
Lipid nanoparticles (LNPs) are commonly employed for drug delivery owing to their considerable drug-loading capacity, low toxicity, and excellent biocompatibility. Nevertheless, the formation of protein corona (PC) on their surfaces significantly influences the drug's in vivo fate (such as absorption, distribution, metabolism, and elimination) upon administration. PC denotes the phenomenon wherein one or multiple strata of proteins adhere to the external interface of nanoparticles (NPs) or microparticles within the biological milieu, encompassing ex vivo fluids (e.g., serum-containing culture media) and in vivo fluids (such as blood and tissue fluids). Hence, it is essential to claim the PC formation behaviors and mechanisms on the surface of LNPs. This overview provided a comprehensive examination of crucial aspects related to such issues, encompassing time evolution, controllability, and their subsequent impacts on LNPs. Classical studies of PC generation on the surface of LNPs were additionally integrated, and its decisive role in shaping the in vivo fate of LNPs was explored. The mechanisms underlying PC formation, including the adsorption theory and alteration theory, were introduced to delve into the formation process. Subsequently, the existing experimental outcomes were synthesized to offer insights into the research and application facets of PC, and it was concluded that the manipulation of PC held substantial promise in the realm of targeted delivery.
脂质纳米颗粒(LNPs)具有相当大的载药量、低毒性和良好的生物相容性,因此被广泛用于药物输送。然而,脂质纳米粒子表面形成的蛋白质电晕(PC)会严重影响给药后药物在体内的转归(如吸收、分布、代谢和消除)。PC 指的是在生物环境中,包括体外体液(如含血清的培养基)和体内体液(如血液和组织液),纳米颗粒或微粒的外部界面上附着一层或多层蛋白质的现象。因此,了解 LNPs 表面 PC 的形成行为和机制至关重要。本综述全面考察了与这些问题相关的关键方面,包括时间演变、可控性及其对 LNPs 的后续影响。此外,还对 LNPs 表面 PC 生成的经典研究进行了整合,并探讨了 PC 在塑造 LNPs 体内命运方面的决定性作用。介绍了 PC 的形成机制,包括吸附理论和改变理论,以深入探讨 PC 的形成过程。随后,综合现有的实验结果,对 PC 的研究和应用方面提出了见解,并得出结论:操纵 PC 在靶向递送领域大有可为。
{"title":"Looking back, moving forward: protein corona of lipid nanoparticles","authors":"Yue Gao, Yeqi Huang, Chuanyu Ren, Peiwen Chou, Chuanbin Wu, Xin Pan, Guilan Quan and Zhengwei Huang","doi":"10.1039/D4TB00186A","DOIUrl":"10.1039/D4TB00186A","url":null,"abstract":"<p >Lipid nanoparticles (LNPs) are commonly employed for drug delivery owing to their considerable drug-loading capacity, low toxicity, and excellent biocompatibility. Nevertheless, the formation of protein corona (PC) on their surfaces significantly influences the drug's <em>in vivo</em> fate (such as absorption, distribution, metabolism, and elimination) upon administration. PC denotes the phenomenon wherein one or multiple strata of proteins adhere to the external interface of nanoparticles (NPs) or microparticles within the biological milieu, encompassing <em>ex vivo</em> fluids (<em>e.g.</em>, serum-containing culture media) and <em>in vivo</em> fluids (such as blood and tissue fluids). Hence, it is essential to claim the PC formation behaviors and mechanisms on the surface of LNPs. This overview provided a comprehensive examination of crucial aspects related to such issues, encompassing time evolution, controllability, and their subsequent impacts on LNPs. Classical studies of PC generation on the surface of LNPs were additionally integrated, and its decisive role in shaping the <em>in vivo</em> fate of LNPs was explored. The mechanisms underlying PC formation, including the adsorption theory and alteration theory, were introduced to delve into the formation process. Subsequently, the existing experimental outcomes were synthesized to offer insights into the research and application facets of PC, and it was concluded that the manipulation of PC held substantial promise in the realm of targeted delivery.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140965034","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}
Panpan Sun, Hai-Chao Chen, Wenting Guo, Zefan Zhang, Shihao Sun, Ningshuang Gao, Yu-Hong Jing and Baodui Wang
Abnormal neuronal polarity leads to early deficits in Alzheimer's disease (AD) by affecting the function of axons. Precise and rapid evaluation of polarity changes is very important for the early prevention and diagnosis of AD. However, due to the limitations of existing detection methods, the mechanism related to how neuronal polarity changes in AD is unclear. Herein, we reported a ratiometric fluorescent probe characterized by neutral molecule to disclose the polarity changes in nerve cells and the brain of APP/PS1 mice. Cy7-K showed a sensitive and selective ratiometric fluorescence response to polarity. Remarkably, unlike conventional intramolecular charge transfer fluorescent probes, the fluorescence quantum yield of Cy7-K in highly polar solvents is higher than that in low polar solvents due to the transition of neutral quinones to aromatic zwitterions. Using the ratiometric fluorescence imaging, we found that beta-amyloid protein (Aβ) inhibits the expression of histone deacetylase 6, thereby increasing the amount of acetylated Tau protein (AC-Tau) and ultimately enhancing cell polarity. There was a high correlation between polarity and AC-Tau. Furthermore, Cy7-K penetrated the blood–brain barrier to image the polarity of different brain regions and confirmed that APP/PS1 mice had higher polarity than Wild-type mice. The probe Cy7-K will be a promising tool for assessing the progression of AD development by monitoring polarity.
{"title":"A ratiometric fluorescent probe revealing the abnormality of acetylated tau by visualizing polarity in Alzheimer's disease†","authors":"Panpan Sun, Hai-Chao Chen, Wenting Guo, Zefan Zhang, Shihao Sun, Ningshuang Gao, Yu-Hong Jing and Baodui Wang","doi":"10.1039/D4TB00357H","DOIUrl":"10.1039/D4TB00357H","url":null,"abstract":"<p >Abnormal neuronal polarity leads to early deficits in Alzheimer's disease (AD) by affecting the function of axons. Precise and rapid evaluation of polarity changes is very important for the early prevention and diagnosis of AD. However, due to the limitations of existing detection methods, the mechanism related to how neuronal polarity changes in AD is unclear. Herein, we reported a ratiometric fluorescent probe characterized by neutral molecule to disclose the polarity changes in nerve cells and the brain of APP/PS1 mice. <strong>Cy7-K</strong> showed a sensitive and selective ratiometric fluorescence response to polarity. Remarkably, unlike conventional intramolecular charge transfer fluorescent probes, the fluorescence quantum yield of <strong>Cy7-K</strong> in highly polar solvents is higher than that in low polar solvents due to the transition of neutral quinones to aromatic zwitterions. Using the ratiometric fluorescence imaging, we found that beta-amyloid protein (Aβ) inhibits the expression of histone deacetylase 6, thereby increasing the amount of acetylated Tau protein (AC-Tau) and ultimately enhancing cell polarity. There was a high correlation between polarity and AC-Tau. Furthermore, <strong>Cy7-K</strong> penetrated the blood–brain barrier to image the polarity of different brain regions and confirmed that APP/PS1 mice had higher polarity than Wild-type mice. The probe <strong>Cy7-K</strong> will be a promising tool for assessing the progression of AD development by monitoring polarity.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072486","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}
Kehua Jiang, Jian Wu, Qing Wang, Xiaolong Chen, Yanlong Zhang, Xiaoya Gu and Kun Tang
Cancer immunotherapy, as an emerging approach to cancer treatment, has tremendous potential for application. Compared to traditional methods such as surgery, chemotherapy, and radiation therapy, it has the ability to restore the patient's immune system, leading to long-term immune memory with less damage to normal tissues. However, immunotherapy has its limitations, including limited therapeutic efficacy, restricted patient populations, and inconsistent treatment responses. Finding effective immunotherapeutic approaches has become a key focus of its clinical application. The adenosine pathway is a recently discovered tumor immune regulatory signaling pathway. It can influence the metabolism and growth of tumor cells by acting through key enzymes in the adenosine pathway, thereby affecting the development of tumors. Therefore, inhibiting the adenosine pathway is an effective cancer immunotherapy. Common adenosine pathway inhibitors include small molecules and antibody proteins, and extensive preclinical trials have demonstrated their effectiveness in inhibiting tumor growth. The short half-life, low bioavailability, and single administration route of adenosine pathway inhibitors limit their clinical application. With the advent of nanotechnology, nano-delivery of adenosine pathway inhibitors has addressed these issues. Compared to traditional drugs, nano-drugs extend the drug's circulation time and improve its distribution within the body. They also offer targeting capabilities and have low toxic side effects, making them very promising for future applications. In this review, we discuss the mechanism of the adenosine pathway in tumor immune suppression, the clinical applications of adenosine pathway inhibitors, and nano-delivery based on adenosine pathway inhibitors. In the final part of this article, we also briefly discuss the technical issues and challenges currently present in nano-delivery of adenosine pathway inhibitors, with the hope of advancing the progress of adenosine inhibitor nano-drugs in clinical treatment.
{"title":"Nanoparticles targeting the adenosine pathway for cancer immunotherapy","authors":"Kehua Jiang, Jian Wu, Qing Wang, Xiaolong Chen, Yanlong Zhang, Xiaoya Gu and Kun Tang","doi":"10.1039/D4TB00292J","DOIUrl":"10.1039/D4TB00292J","url":null,"abstract":"<p >Cancer immunotherapy, as an emerging approach to cancer treatment, has tremendous potential for application. Compared to traditional methods such as surgery, chemotherapy, and radiation therapy, it has the ability to restore the patient's immune system, leading to long-term immune memory with less damage to normal tissues. However, immunotherapy has its limitations, including limited therapeutic efficacy, restricted patient populations, and inconsistent treatment responses. Finding effective immunotherapeutic approaches has become a key focus of its clinical application. The adenosine pathway is a recently discovered tumor immune regulatory signaling pathway. It can influence the metabolism and growth of tumor cells by acting through key enzymes in the adenosine pathway, thereby affecting the development of tumors. Therefore, inhibiting the adenosine pathway is an effective cancer immunotherapy. Common adenosine pathway inhibitors include small molecules and antibody proteins, and extensive preclinical trials have demonstrated their effectiveness in inhibiting tumor growth. The short half-life, low bioavailability, and single administration route of adenosine pathway inhibitors limit their clinical application. With the advent of nanotechnology, nano-delivery of adenosine pathway inhibitors has addressed these issues. Compared to traditional drugs, nano-drugs extend the drug's circulation time and improve its distribution within the body. They also offer targeting capabilities and have low toxic side effects, making them very promising for future applications. In this review, we discuss the mechanism of the adenosine pathway in tumor immune suppression, the clinical applications of adenosine pathway inhibitors, and nano-delivery based on adenosine pathway inhibitors. In the final part of this article, we also briefly discuss the technical issues and challenges currently present in nano-delivery of adenosine pathway inhibitors, with the hope of advancing the progress of adenosine inhibitor nano-drugs in clinical treatment.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285748","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}
Mariam Hohagen, Nuno Saraiva, Hanspeter Kählig, Christopher Gerner, Giorgia Del Favero and Freddy Kleitz
Gallic acid (GA), derived from land plants, possesses diverse physiological benefits, including anti-inflammatory and anticancer effects, making it valuable for biomedical applications. In this study, GA was used to modify the surface of dendritic mesoporous silica nanoparticles (DMSNs) via carbamate (DMSN-NCO-GA) or amide (DMSN-NH-GA) bonds, using a post-grafting technique. To explore GA-conjugated materials' potential in modulating cancer cell redox status, three variants of osteosarcoma cells (U2-OS) were used. These variants comprised the wild-type cells (NEO), the cells overexpressing the wild-type human Golgi anti-apoptotic protein (hGAAP), and the null mutant of hGAAP (Ct-mut), as this protein was previously demonstrated to play a role in intracellular reactive oxygen species (ROS) accumulation and cell migration. In the absence of external ROS triggers, non-modified DMSNs increased intracellular ROS in Ct-mut and NEO cells, while GA-conjugated materials, particularly DMSN-NH-GA, significantly reduced ROS levels, especially pronounced with higher GA concentrations and notably in hGAAP cells with inherently higher ROS levels. Additionaly, NH-GA conjugates were less cytotoxic, more effective in reducing cell migration, and had higher ROS buffering capacity compared to DMSN-NCO-GA materials. However, in the presence of the external stressor tert-butyl-hydroperoxide (TBHP), NCO-GA conjugates showed more efficient reduction of intracellular ROS. These findings suggest that varying chemical decoration strategies of nanomaterials, along with the accessibility of functional groups to the cellular environment, significantly influence the biological response in osteosarcoma cells. Highlighting this, GA-conjugation is a promising method for implementing antioxidant properties and inhibiting cancer cell migration, warranting further research in anticancer treatment and drug development.
{"title":"Silica nanoparticle conjugation with gallic acid towards enhanced free radical scavenging capacity and activity on osteosarcoma cells in vitro†","authors":"Mariam Hohagen, Nuno Saraiva, Hanspeter Kählig, Christopher Gerner, Giorgia Del Favero and Freddy Kleitz","doi":"10.1039/D4TB00151F","DOIUrl":"10.1039/D4TB00151F","url":null,"abstract":"<p >Gallic acid (GA), derived from land plants, possesses diverse physiological benefits, including anti-inflammatory and anticancer effects, making it valuable for biomedical applications. In this study, GA was used to modify the surface of dendritic mesoporous silica nanoparticles (DMSNs) <em>via</em> carbamate (DMSN-NCO-GA) or amide (DMSN-NH-GA) bonds, using a post-grafting technique. To explore GA-conjugated materials' potential in modulating cancer cell redox status, three variants of osteosarcoma cells (U2-OS) were used. These variants comprised the wild-type cells (NEO), the cells overexpressing the wild-type human Golgi anti-apoptotic protein (hGAAP), and the null mutant of hGAAP (Ct-mut), as this protein was previously demonstrated to play a role in intracellular reactive oxygen species (ROS) accumulation and cell migration. In the absence of external ROS triggers, non-modified DMSNs increased intracellular ROS in Ct-mut and NEO cells, while GA-conjugated materials, particularly DMSN-NH-GA, significantly reduced ROS levels, especially pronounced with higher GA concentrations and notably in hGAAP cells with inherently higher ROS levels. Additionaly, NH-GA conjugates were less cytotoxic, more effective in reducing cell migration, and had higher ROS buffering capacity compared to DMSN-NCO-GA materials. However, in the presence of the external stressor <em>tert</em>-butyl-hydroperoxide (TBHP), NCO-GA conjugates showed more efficient reduction of intracellular ROS. These findings suggest that varying chemical decoration strategies of nanomaterials, along with the accessibility of functional groups to the cellular environment, significantly influence the biological response in osteosarcoma cells. Highlighting this, GA-conjugation is a promising method for implementing antioxidant properties and inhibiting cancer cell migration, warranting further research in anticancer treatment and drug development.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/tb/d4tb00151f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302321","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}
Baohang Lin, Xun Peng, Jianjun Cheng and Jiacheng Wang
Gambogic acid (GA) as a naturally derived chemotherapeutic agent is of increasing interest for antitumor therapy. However, current research mainly focuses on improving the pharmacological properties to overcome the shortcomings in clinical applications or as a synergistic anticancer agent in combination with chemotherapy and chemophototherapy. Yet, the material properties of GA (e.g., self-assembly) are often neglected. Herein, we validated the self-assembly function of GA and its huge potential as a single-component active carrier for synergistic delivery using pyropheophorbide-a (PPa) as a drug model. The results showed that self-assembled GA drives the formation of nano-GA/PPa mainly through noncovalent interactions such as π–π stacking, hydrophobic interactions, and hydrogen bonding. Additionally, although no significant differences in cytotoxicity were found between the individual in vitro chemotherapy and combined chemophototherapy, the as-prepared nano-GA/PPa exhibits remarkably improved water solubility and multiple favorable therapeutic features, leading to a prominent in vivo photochemotherapy efficiency of 89.3% inhibition rate with reduced hepatotoxicity of GA. This work highlights the potential of self-assembled GA as a drug delivery carrier for synergistic biomedical applications.
甘草酸(GA)作为一种天然衍生的化疗药物,在抗肿瘤治疗中越来越受到关注。然而,目前的研究主要集中在改善其药理特性,以克服临床应用中的不足,或将其作为一种与化疗和化学光疗相结合的协同抗癌剂。然而,GA 的材料特性(如自组装)往往被忽视。在此,我们以吡咯并烯酮-a(PPa)为药物模型,验证了天麻的自组装功能及其作为单组分活性载体协同递送的巨大潜力。结果表明,自组装的 GA 主要通过π-π堆积、疏水作用和氢键等非共价相互作用推动纳米-GA/PPa 的形成。此外,虽然单独体外化疗和联合化学光疗在细胞毒性方面没有发现明显差异,但制备的纳米GA/PPa表现出显著的水溶性和多种有利的治疗特性,从而使体内光化学疗法的抑制率达到89.3%,并降低了GA的肝毒性。这项工作凸显了自组装 GA 作为药物递送载体在协同生物医学应用方面的潜力。
{"title":"Natural gambogic acid-tuned self-assembly of nanodrugs towards synergistic chemophototherapy against breast cancer†","authors":"Baohang Lin, Xun Peng, Jianjun Cheng and Jiacheng Wang","doi":"10.1039/D4TB00364K","DOIUrl":"10.1039/D4TB00364K","url":null,"abstract":"<p >Gambogic acid (GA) as a naturally derived chemotherapeutic agent is of increasing interest for antitumor therapy. However, current research mainly focuses on improving the pharmacological properties to overcome the shortcomings in clinical applications or as a synergistic anticancer agent in combination with chemotherapy and chemophototherapy. Yet, the material properties of GA (<em>e.g.</em>, self-assembly) are often neglected. Herein, we validated the self-assembly function of GA and its huge potential as a single-component active carrier for synergistic delivery using pyropheophorbide-a (PPa) as a drug model. The results showed that self-assembled GA drives the formation of nano-GA/PPa mainly through noncovalent interactions such as π–π stacking, hydrophobic interactions, and hydrogen bonding. Additionally, although no significant differences in cytotoxicity were found between the individual <em>in vitro</em> chemotherapy and combined chemophototherapy, the as-prepared nano-GA/PPa exhibits remarkably improved water solubility and multiple favorable therapeutic features, leading to a prominent <em>in vivo</em> photochemotherapy efficiency of 89.3% inhibition rate with reduced hepatotoxicity of GA. This work highlights the potential of self-assembled GA as a drug delivery carrier for synergistic biomedical applications.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159349","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}
In cardiac tissue engineering, myocardial surface patches and hydrogel intramyocardial injections represent the two primary hydrogel-based strategies for myocardial infarction (MI) treatment. However, the comparative effectiveness of these two treatments remains uncertain. Therefore, this study aimed to compare the effects of the two treatment modalities by designing a simple and reproducible hydrogel cross-linked with γ-PGA and 4-arm-PEG-SG. To improve mitochondrial damage in cardiomyocytes (CMs) during early MI, we incorporated the mitochondria-targeting antioxidant MitoQ into the hydrogel network. The hydrogel exhibited excellent biodegradability, biocompatibility, adhesion, and injectability in vitro. The hydrogel was utilized for rat MI treatment through both patch adhesion and intramyocardial injections. In vivo results demonstrated that the slow release of MitoQ peptide from the hydrogel hindered ROS production in CM, alleviated mitochondrial damage, and enhanced CM activity within 7 days, effectively inhibiting MI progression. Both hydrogel intramyocardial injections and patches exhibited positive therapeutic effects, with intramyocardial injections demonstrating superior efficacy in terms of cardiac function and structure in equivalent treatment cycles. In conclusion, we developed a MitoQ/hydrogel system that is easily prepared and can serve as both a myocardial patch and an intramyocardial injection for MI treatment, showing significant potential for clinical applications.
在心脏组织工程中,心肌表面贴片和心肌内注射水凝胶是治疗心肌梗塞(MI)的两种主要水凝胶策略。然而,这两种治疗方法的比较效果仍不确定。因此,本研究旨在通过设计一种简单且可重复的γ-PGA和4-arm-PEG-SG交联水凝胶来比较两种治疗方式的效果。为了改善心肌梗死早期心肌细胞(CMs)的线粒体损伤,我们在水凝胶网络中加入了线粒体靶向抗氧化剂 MitoQ。这种水凝胶在体外表现出良好的生物降解性、生物相容性、粘附性和注射性。通过贴片粘附和心肌内注射,该水凝胶被用于大鼠心肌梗死的治疗。体内研究结果表明,水凝胶中 MitoQ 肽的缓慢释放可在 7 天内阻碍 CM 中 ROS 的产生,减轻线粒体损伤,增强 CM 活性,从而有效抑制心肌梗死的进展。水凝胶心肌内注射和贴片均显示出积极的治疗效果,其中心肌内注射在同等治疗周期内对心脏功能和结构的疗效更佳。总之,我们开发的 MitoQ/水凝胶系统易于制备,既可作为心肌贴片,也可作为心肌内注射治疗心肌梗死,在临床应用方面具有巨大潜力。
{"title":"Comparative effectiveness of myocardial patches and intramyocardial injections in treating myocardial infarction with a MitoQ/hydrogel system","authors":"Ying Tan, Yali Nie, Lei ZhengWen and Zhi Zheng","doi":"10.1039/D4TB00573B","DOIUrl":"10.1039/D4TB00573B","url":null,"abstract":"<p >In cardiac tissue engineering, myocardial surface patches and hydrogel intramyocardial injections represent the two primary hydrogel-based strategies for myocardial infarction (MI) treatment. However, the comparative effectiveness of these two treatments remains uncertain. Therefore, this study aimed to compare the effects of the two treatment modalities by designing a simple and reproducible hydrogel cross-linked with γ-PGA and 4-arm-PEG-SG. To improve mitochondrial damage in cardiomyocytes (CMs) during early MI, we incorporated the mitochondria-targeting antioxidant MitoQ into the hydrogel network. The hydrogel exhibited excellent biodegradability, biocompatibility, adhesion, and injectability <em>in vitro</em>. The hydrogel was utilized for rat MI treatment through both patch adhesion and intramyocardial injections. <em>In vivo</em> results demonstrated that the slow release of MitoQ peptide from the hydrogel hindered ROS production in CM, alleviated mitochondrial damage, and enhanced CM activity within 7 days, effectively inhibiting MI progression. Both hydrogel intramyocardial injections and patches exhibited positive therapeutic effects, with intramyocardial injections demonstrating superior efficacy in terms of cardiac function and structure in equivalent treatment cycles. In conclusion, we developed a MitoQ/hydrogel system that is easily prepared and can serve as both a myocardial patch and an intramyocardial injection for MI treatment, showing significant potential for clinical applications.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072487","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}
Diabetic foot ulcers are a significant complication affecting roughly 15% of diabetic patients. These chronic wounds can be incredibly burdensome, leading to high treatment costs, potential amputations, and additional health complications. Microbiological studies reveal that bacterial infections are the primary culprit behind delayed wound healing. To solve the problem of infection at the wound site, the most fundamental thing is to kill the pathogenic bacteria. Herein, a neoteric strategy to construct novel antibacterial hydrogel COA-T3 that combined photosensitizers (PSs) and antimicrobial peptides (AMPs) via covalent coupling was proposed. Hydrogel COA-T3 composed of quaternized chitosan (QCS) and oxidized dextran (OD) was constructed for co-delivery of the photosensitizer TPI-PN and the antimicrobial peptide HHC10. In vitro and in vivo experiments demonstrated remarkable effectiveness of COA-T3 against drug-resistant bacteria. Furthermore, the hydrogel significantly promoted healing of diabetic infected wounds. This enhanced antibacterial activity is attributed to the pH-sensitive release of both PSs and AMPs within the hydrogel. Additionally, COA-T3 exhibits excellent biocompatibility, making it a promising candidate for wound dressing materials. These findings indicated that the COA-T3 hydrogel is a promising wound dressing material for promoting the healing of diabetic foot ulcers by providing an environment conducive to improved wound healing in diabetic patients.
{"title":"A peptide-based pH-sensitive antibacterial hydrogel for healing drug-resistant biofilm-infected diabetic wounds†","authors":"Duoyang Fan, Ruyan Xie, Xiaohui Liu, Haohan Li, Ziheng Luo, Yanbing Li, Fei Chen and Wenbin Zeng","doi":"10.1039/D4TB00594E","DOIUrl":"10.1039/D4TB00594E","url":null,"abstract":"<p >Diabetic foot ulcers are a significant complication affecting roughly 15% of diabetic patients. These chronic wounds can be incredibly burdensome, leading to high treatment costs, potential amputations, and additional health complications. Microbiological studies reveal that bacterial infections are the primary culprit behind delayed wound healing. To solve the problem of infection at the wound site, the most fundamental thing is to kill the pathogenic bacteria. Herein, a neoteric strategy to construct novel antibacterial hydrogel <strong>COA-T3</strong> that combined photosensitizers (PSs) and antimicrobial peptides (AMPs) <em>via</em> covalent coupling was proposed. Hydrogel <strong>COA-T3</strong> composed of quaternized chitosan (QCS) and oxidized dextran (OD) was constructed for co-delivery of the photosensitizer <strong>TPI-PN</strong> and the antimicrobial peptide <strong>HHC10</strong>. <em>In vitro</em> and <em>in vivo</em> experiments demonstrated remarkable effectiveness of <strong>COA-T3</strong> against drug-resistant bacteria. Furthermore, the hydrogel significantly promoted healing of diabetic infected wounds. This enhanced antibacterial activity is attributed to the pH-sensitive release of both PSs and AMPs within the hydrogel. Additionally, <strong>COA-T3</strong> exhibits excellent biocompatibility, making it a promising candidate for wound dressing materials. These findings indicated that the <strong>COA-T3</strong> hydrogel is a promising wound dressing material for promoting the healing of diabetic foot ulcers by providing an environment conducive to improved wound healing in diabetic patients.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922715","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}
Yikai Chen, Binggang Ye, Mengling Ning, Meng Li, Yixuan Pu, Zhiming Liu, Huiqing Zhong, Chaofan Hu and Zhouyi Guo
Rapid and sensitive detection of food-borne bacteria has remained challenging over the past few decades. We propose a surface-enhanced Raman scattering sensing strategy based on a novel bioinspired surface-enhanced Raman scattering substrate, which can directly detect dye molecular residues and food-borne pathogen microorganisms in the environment. The surface-enhanced Raman scattering platform consists of a natural diatomite microporous array decorated with a metal-phenolic network that enables the in situ reduction of gold nanoparticles. The as-prepared nanocomposites display excellent surface-enhanced Raman scattering activity with the lowest limit of detection and the maximum Raman enhancement factor of dye molecules up to 10−11 M and 1.18 × 107, respectively. For food-borne bacterial detection, a diatomite microporous array decorated with a metal polyphenol network and gold nanoparticle-based surface-enhanced Raman scattering analysis is capable of distinguishing the biochemical fingerprint information of Staphylococcus aureus and Escherichia coli, indicating the great potential for strain identification.
过去几十年来,快速灵敏地检测食源性细菌一直是一项挑战。我们提出了一种基于新型生物启发的表面增强拉曼散射基底的表面增强拉曼散射传感策略,可以直接检测环境中的染料分子残留和食源性病原微生物。该表面增强拉曼散射平台由天然硅藻土微孔阵列组成,阵列上装饰有金属酚网络,可实现金纳米粒子的原位还原。制备的纳米复合材料显示出优异的表面增强拉曼散射活性,染料分子的最低检测限和最大拉曼增强因子分别高达 10-11 M 和 1.18 × 107。在食源性细菌检测方面,用金属多酚网络装饰的硅藻土微孔阵列和基于金纳米粒子的表面增强拉曼散射分析能够区分金黄色葡萄球菌和大肠杆菌的生化指纹信息,表明其在菌种鉴定方面具有巨大潜力。
{"title":"Food-borne bacteria analysis using a diatomite bioinspired SERS platform†","authors":"Yikai Chen, Binggang Ye, Mengling Ning, Meng Li, Yixuan Pu, Zhiming Liu, Huiqing Zhong, Chaofan Hu and Zhouyi Guo","doi":"10.1039/D4TB00488D","DOIUrl":"10.1039/D4TB00488D","url":null,"abstract":"<p >Rapid and sensitive detection of food-borne bacteria has remained challenging over the past few decades. We propose a surface-enhanced Raman scattering sensing strategy based on a novel bioinspired surface-enhanced Raman scattering substrate, which can directly detect dye molecular residues and food-borne pathogen microorganisms in the environment. The surface-enhanced Raman scattering platform consists of a natural diatomite microporous array decorated with a metal-phenolic network that enables the <em>in situ</em> reduction of gold nanoparticles. The as-prepared nanocomposites display excellent surface-enhanced Raman scattering activity with the lowest limit of detection and the maximum Raman enhancement factor of dye molecules up to 10<small><sup>−11</sup></small> M and 1.18 × 10<small><sup>7</sup></small>, respectively. For food-borne bacterial detection, a diatomite microporous array decorated with a metal polyphenol network and gold nanoparticle-based surface-enhanced Raman scattering analysis is capable of distinguishing the biochemical fingerprint information of <em>Staphylococcus aureus</em> and <em>Escherichia coli</em>, indicating the great potential for strain identification.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141163179","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}