Stimuli responsive

刺激反应性
  • 文章类型: Journal Article
    脊髓损伤(SCI)是一种使人衰弱的疾病,可导致严重的功能损害和生活质量丧失。人们对开发SCI的新疗法越来越感兴趣,基于水凝胶的多模式治疗策略已成为一种有前途的方法。它们为SCI修复提供了几个优点,包括生物相容性,可调的机械性能,低免疫原性,以及提供治疗剂的能力。本文概述了基于水凝胶的SCI修复治疗策略的最新进展,特别是在过去的三年里。我们总结了具有不同特性的SCI水凝胶,如相变水凝胶,自愈水凝胶,定向纤维水凝胶,和自组装微球水凝胶,以及不同的功能水凝胶,如导电水凝胶,刺激响应性水凝胶,粘合剂水凝胶,抗氧化水凝胶,缓释水凝胶,等。组成,准备,并对这些水凝胶的治疗效果进行了简要讨论和综合评价。最后,展望了水凝胶在SCI修复中的未来发展,以激发更多的研究人员在这一前景广阔的领域进行投资。
    Spinal cord injury (SCI) is a debilitating condition that can result in significant functional impairment and loss of quality of life. There is a growing interest in developing new therapies for SCI, and hydrogel-based multimodal therapeutic strategies have emerged as a promising approach. They offer several advantages for SCI repair, including biocompatibility, tunable mechanical properties, low immunogenicity, and the ability to deliver therapeutic agents. This article provides an overview of the recent advances in hydrogel-based therapy strategies for SCI repair, particularly within the past three years. We summarize the SCI hydrogels with varied characteristics such as phase-change hydrogels, self-healing hydrogel, oriented fibers hydrogel, and self-assembled microspheres hydrogel, as well as different functional hydrogels such as conductive hydrogels, stimuli-responsive hydrogels, adhesive hydrogel, antioxidant hydrogel, sustained-release hydrogel, etc. The composition, preparation, and therapeutic effect of these hydrogels are briefly discussed and comprehensively evaluated. In the end, the future development of hydrogels in SCI repair is prospected to inspire more researchers to invest in this promising field.
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  • 文章类型: Journal Article
    离子液体在新型材料的设计中起着至关重要的作用。IL的离子性质在药物递送中提供了许多优点。作为绿色溶剂或活性成分,以提高溶解度,渗透性,和药物的结合效率。它们还可以在用于药物递送的纳米/微米颗粒的开发中充当结构化剂,包括胶束,囊泡,凝胶,乳液,还有更多.本文综述了IL和基于IL的凝胶结构及其先进的药物递送应用。综述的第一部分重点介绍了ILs在药物配制中的作用以及ILs在药物输送中的应用。综述的第二部分全面概述了基于IL的凝胶的最新药物递送应用。它旨在提供新的观点并吸引更多的关注,以开辟IL和基于IL的凝胶的生物医学应用的新途径。
    Ionic liquids (ILs) play a crucial role in the design of novel materials. The ionic nature of ILs provides numerous advantages in drug delivery, acting as a green solvent or active ingredient to enhance the solubility, permeability, and binding efficiency of drugs. They could also function as a structuring agent in the development of nano/micro particles for drug delivery, including micelles, vesicles, gels, emulsion, and more. This review summarize the ILs and IL-based gel structures with their advanced drug delivery applications. The first part of review focuses on the role of ILs in drug formulation and the applications of ILs in drug delivery. The second part of review offers a comprehensive overview of recent drug delivery applications of IL-based gel. It aims to offer new perspectives and attract more attention to open up new avenues in the biomedical applications of ILs and IL-based gels.
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  • 文章类型: Journal Article
    目的:设计并评估基质金属蛋白酶9(MMP-9)响应性水凝胶,用于重要牙髓治疗。
    方法:通过巯基-降冰片烯光聚合将对MMP-9具有优化敏感性的肽接头与4臂聚(乙二醇)-降冰片烯(PEG-NB)交联。这导致其中掺入肽IDR-1002的水凝胶网络的形成。用傅里叶变换红外光谱研究了水凝胶的表征和凝胶动力学,扫描电子显微镜,流变测试,和肿胀评估。通过多次暴露于预活化的MMP-9来检查水凝胶降解,以模拟牙髓炎症的爆发。用高效液相色谱法测量从降解的水凝胶释放的IDR-1002。使用共聚焦激光扫描显微镜评估从水凝胶释放的IDR-1002对一周大的多物种口腔生物膜的影响。
    结果:MMP-9反应,可注射,并成功合成了光交联水凝胶。当在暴露于预先活化的MMP-9的情况下检查IDR-1002的水凝胶降解和释放时,IDR-1002的释放与MMP-9水平的升高显著相关(p<0.05)。与浸入磷酸盐缓冲盐水相比,当水凝胶浸入10nM或20nM预活化的MMP-9中时,IDR-1002杀死多物种口腔生物膜的有效性显著增强(p<0.05)。
    结论:MMP-9响应性水凝胶是重要牙髓治疗中按需递送生物活性剂的有希望的候选者。
    结论:MMP-9是牙髓炎最重要的诊断和预后生物标志物之一。MMP-9响应性水凝胶具有用作诊断和治疗牙髓炎症的原位按需释放系统的潜力。
    To design and evaluate a matrix metalloproteinase 9 (MMP-9)-responsive hydrogel for vital pulp therapy.
    A peptide linker with optimized sensitivity toward MMP-9 was crosslinked with 4-arm poly (ethylene glycol)-norbornene (PEG-NB) by thiol-norbornene photo-polymerization. This resulted in the formation of a hydrogel network in which the peptide IDR-1002 was incorporated. Hydrogel characterization and gelation kinetics were examined with Fourier-transform infrared spectroscopy, scanning electron microscopy, rheological testing, and swelling evaluation. Hydrogel degradation was examined through multiple exposure to pre-activated MMP-9, to simulate flare-ups of dental pulp inflammation. The IDR-1002 released from degraded hydrogels was measured with high-performance liquid chromatography. Effect of IDR-1002 released from hydrogels on one-week-old multispecies oral biofilms was evaluated using confocal laser scanning microscopy.
    MMP-9-responsive, injectable, and photo-crosslinkable hydrogels were successfully synthesized. When hydrogel degradation and release of IDR-1002 were examined with exposure to pre-activated MMP-9, IDR-1002 release was significantly correlated with elevated levels of MMP-9 (p < 0.05). The effectiveness of IDR-1002 in killing bacteria in multispecies oral biofilms was significantly enhanced when the hydrogels were immersed in 10 nM or 20 nM pre-activated MMP-9, compared to immersion in phosphate-buffered saline (p < 0.05).
    The MMP-9-responsive hydrogel is a promising candidate for on-demand delivery of bioactive agent in vital pulp therapy.
    MMP-9 is one of the most important diagnostic and prognostic biomarkers for pulpitis. An MMP-9-responsive hydrogel has potential to be used as an in-situ on-demand release system for the diagnosis and treatment of dental pulp inflammation.
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  • 文章类型: Journal Article
    纳米技术支持的农药递送系统已被广泛研究,并在现代农业中显示出巨大的前景。纳米递送系统不仅实现了农用化学品的控制释放,而且具有许多独特的特性。这项研究提出了利用中空介孔二氧化硅纳米颗粒(HMSNs)作为纳米载体的pH响应型农药纳米制剂的开发。纳米载体负载有光敏农药丙草胺(Pro),然后通过静电相互作用与ZnO量子点(ZnO量子点)结合。ZnOQD既是pH响应性的看门人,也是农药的增强剂。结果表明,所制备的纳米农药对Pro具有较高的负载效率(24.96%)。与Pro技术相比,负载在HMSNs@Pro@ZnOQDs中的Pro在24h紫外线(UV)暴露后降解率降低了26.4%,表明明显改进的光稳定性。在弱酸性环境(pH5.0)中,48小时后纳米农药的累积释放量比中性环境高2.67倍。这表明纳米农药具有优异的pH响应特性。跟踪实验表明,HMSN可以被水稻叶片吸收,然后运输到其他组织,表明它们有效的全身分布和有针对性的递送的潜力。此外,生物活性试验证实了纳米农药对稻瘟病的杀菌效力。因此,构建的纳米农药在纳米农业中具有广阔的前景,提供了一种提高农药利用率的新策略。
    Nanotechnology-enabled pesticide delivery systems have been widely studied and show great prospects in modern agriculture. Nanodelivery systems not only achieve the controlled release of agrochemicals but also possess many unique characteristics. This study presents the development of a pH-responsive pesticide nanoformulation utilizing hollow mesoporous silica nanoparticles (HMSNs) as a nanocarrier. The nanocarrier was loaded with the photosensitive pesticide prochloraz (Pro) and then combined with ZnO quantum dots (ZnO QDs) through electrostatic interactions. ZnO QDs serve as both the pH-responsive gatekeeper and the enhancer of the pesticide. The results demonstrate that the prepared nanopesticide exhibits high loading efficiency (24.96%) for Pro. Compared with Pro technical, the degradation rate of Pro loaded in HMSNs@Pro@ZnO QDs was reduced by 26.4% after 24 h ultraviolet (UV) exposure, indicating clearly improved photostability. In a weak acidic environment (pH 5.0), the accumulated release of the nanopesticide after 48 h was 2.67-fold higher than that in a neutral environment. This indicates the excellent pH-responsive characteristic of the nanopesticide. The tracking experiments revealed that HMSNs can be absorbed by rice leaves and subsequently transported to other tissues, indicating their potential for effective systemic distribution and targeted delivery. Furthermore, the bioactivity assays confirmed the fungicidal efficacy of the nanopesticide against rice blast disease. Therefore, the constructed nanopesticide holds great prospect in nanoenabled agriculture, offering a novel strategy to enhance pesticide utilization.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    癌症仍然是全球死亡的主要原因之一,缺乏有效的治疗。常规疗法在肿瘤特异性和非特异性毒性方面的固有缺点促使我们寻找替代疗法来减轻这些限制。在这方面,我们开发了多功能双金属(FeCo)双MIL-88B-FCMOFs修饰的叶酸偶联壳聚糖(FC)作为药物递送系统(DDS)靶向递送5-氟尿嘧啶(5-FU)。双MIL-88B纳米载体通过各种技术进行了表征,包括粉末X射线衍射,扫描电子显微镜,能量色散X射线,热重分析,和傅里叶变换红外光谱。有趣的是,与未改性的5-FU@bi-MIL-88B相比,由于FC表面涂层赋予的门控效应现象,5-FU@bi-MIL-88B-FC显示出较慢的5-FU释放。观察到pH响应的药物释放,58%的加载的5-FU在模拟pH(5.2)的癌细胞中释放,而在生理pH下仅释放24.9%(5.4)。体外细胞毒性和细胞内化实验揭示了5-FU@bi-MIL-88B-FC作为针对叶酸受体(FR)阳性SW480癌细胞的高效靶向DDS的优越性。此外,由于结构中存在Fe和Co,bi-MIL-88B表现出用于化学动力学治疗的过氧化物酶样活性。根据结果,5-FU@bi-MIL-88B-FC可以通过持续的药物释放和选择性靶向作为智能DDS的有希望的候选物。
    Cancer has remained one of the leading causes of death worldwide, with a lack of effective treatment. The intrinsic shortcomings of conventional therapeutics regarding tumor specificity and non-specific toxicity prompt us to look for alternative therapeutics to mitigate these limitations. In this regard, we developed multifunctional bimetallic (FeCo) bi-MIL-88B-FC MOFs modified with folic acid-conjugated chitosan (FC) as drug delivery systems (DDS) for targeted delivery of 5-Fluorouracil (5-FU). The bi-MIL-88B nanocarriers were characterized through various techniques, including powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Interestingly, 5-FU@bi-MIL-88B-FC showed slower release of 5-FU due to a gated effect phenomenon endowed by FC surface coating compared to un-modified 5-FU@bi-MIL-88B. The pH-responsive drug release was observed, with 58% of the loaded 5-FU released in cancer cells mimicking pH (5.2) compared to only 24.9% released under physiological pH (5.4). The in vitro cytotoxicity and cellular internalization experiments revealed the superiority of 5-FU@bi-MIL-88B-FC as a highly potent targeted DDS against folate receptor (FR) positive SW480 cancer cells. Moreover, due to the presence of Fe and Co in the structure, bi-MIL-88B exhibited peroxidase-like activity for chemodynamic therapy. Based on the results, 5-FU@bi-MIL-88B-FC could serve as promising candidate for smart DDS by sustained drug release and selective targeting.
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  • 文章类型: Journal Article
    肿瘤微环境(TME)的复杂性严重阻碍了各种癌症治疗方式的治疗效果。由于缺氧的存在,TME与正常组织不同,低pH值,和免疫抑制特性。调节TME以逆转肿瘤生长平衡被认为是治疗肿瘤的有效方法。最近,聚合物纳米药物已广泛用于癌症治疗,因为它们的合成可以控制,而且它们是高度可修改的,并显示出重塑TME的巨大潜力。在这次审查中,我们概述了各种刺激响应性聚合物纳米药物在调节TME中的应用,旨在为下一代聚合物纳米药物的设计提供见解,促进聚合物纳米药物用于癌症治疗的发展。
    The complexity of the tumor microenvironment (TME) severely hinders the therapeutic effects of various cancer treatment modalities. The TME differs from normal tissues owing to the presence of hypoxia, low pH, and immune-suppressive characteristics. Modulation of the TME to reverse tumor growth equilibrium is considered an effective way to treat tumors. Recently, polymeric nanomedicines have been widely used in cancer therapy, because their synthesis can be controlled and they are highly modifiable, and have demonstrated great potential to remodel the TME. In this review, we outline the application of various stimuli responsive polymeric nanomedicines to modulate the TME, aiming to provide insights for the design of the next generation of polymeric nanomedicines and promote the development of polymeric nanomedicines for cancer therapy.
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  • 文章类型: Journal Article
    化疗药物多柔比星(DOX)已经见证了用于治疗各种癌症的广泛应用。DOX处理的垂死细胞具有细胞修饰,可增强肿瘤抗原的呈递和邻近的树突状细胞的活化。此外,DOX还促进免疫介导的肿瘤细胞清除。然而,缺点,如严重的脱靶毒性,和突出的疏水性导致不令人满意的临床治疗结果。尽管纳米技术和生物材料的快速发展,DOX药物分子的有效递送仍然具有挑战性。巨大的进步已经见证了DOX纳米前药由于其辉煌的好处,如肿瘤刺激响应的药物释放能力,具有载药效率高等特点。本文综述了基于DOX前药的纳米药物的最新进展,为未来的发展提供了深刻的见解,并激励研究人员探索具有实际临床应用的DOX纳米前药。
    The chemotherapeutic drug of doxorubicin (DOX) has witnessed widespread applications for treating various cancers. DOX-treated dying cells bear cellular modifications which allow enhanced presentation of tumor antigen and neighboring dendritic cell activation. Furthermore, DOX also facilitate the immune-mediated clearance of tumor cells. However, disadvantages such as severe off-target toxicity, and prominent hydrophobicity have resulted in unsatisfactory clinical therapeutic outcomes. The effective delivery of DOX drug molecules is still challenging despite the rapid advances in nanotechnology and biomaterials. Huge progress has been witnessed in DOX nanoprodrugs owing to their brilliant benefits such as tumor stimuli-responsive drug release capacity, high drug loading efficiency and so on. This review summarized recent progresses of DOX prodrug-based nanomedicines to provide deep insights into future development and inspire researchers to explore DOX nanoprodrugs with real clinical applications.
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  • 文章类型: Journal Article
    谷胱甘肽(GSH)消耗增强的癌症疗法代表了重要的潜在癌症治疗策略。在这里,我们开发了一种新型多功能的双硒化物交联水凝胶,其具有类似谷胱甘肽过氧化物酶(GPx)的催化活性,可用于GSH耗竭增强的葡萄糖氧化酶(GOx)介导的肿瘤饥饿和缺氧激活的化疗.通过在GOx诱导的肿瘤饥饿期间增加酸和H2O2,可以促进多响应支架的降解,这导致装载药物的加速释放。同时,在降解水凝胶释放的小分子硒化物的级联催化下,过量产生的H2O2导致细胞内GSH消耗加速,进一步增强原位H2O2和后续多模式癌症治疗的疗效。在GOx诱导的缺氧扩增后,替拉嗪(TPZ)转化为高毒性的苯并三嗪基(BTZ·),表现出增强的抗肿瘤活性。这种GSH消耗增强的癌症治疗策略有效地促进了GOx介导的肿瘤饥饿并激活了缺氧药物,导致局部抗癌功效显著增强。重要性声明:人们对消耗细胞内GSH作为改善基于ROS的癌症治疗的潜在策略越来越感兴趣。在这里,开发了一种具有GPx样催化活性的生物响应性二硒化物功能化葡聚糖基水凝胶,用于GSH消耗增强的局部饥饿和缺氧激活的黑色素瘤治疗.结果表明,在降解水凝胶释放的小分子硒化物的级联催化下,过量产生的H2O2导致细胞内GSH消耗加速,进一步增强原位H2O2和后续多模式癌症治疗的疗效。
    Glutathione (GSH) consumption-enhanced cancer therapies represent important potential cancer treatment strategies. Herein, we developed a new multifunctional diselenide-crosslinked hydrogel with glutathione peroxidase (GPx)-like catalytic activity for GSH depletion-enhanced glucose oxidase (GOx)-mediated tumor starvation and hypoxia-activated chemotherapy. By increasing acid and H2O2 during GOx-induced tumor starvation, the degradation of the multiresponsive scaffold could be promoted, which led to accelerated release of the loaded drugs. Meanwhile, the overproduced H2O2 led to accelerated intracellular GSH consumption under the cascade catalysis of small molecular selenides released from the degraded hydrogel, further enhancing the curative effect of in situ H2O2 and subsequent multimodal cancer treatment. Following the GOx-induced amplification of hypoxia, tirapazamine (TPZ) was transformed into the highly toxic benzotriazinyl radical (BTZ·), exhibiting enhanced antitumor activity. This GSH depletion-augmented cancer treatment strategy effectively boosted GOx-mediated tumor starvation and activated the hypoxia drug, leading to significantly enhanced local anticancer efficacy. STATEMENT OF SIGNIFICANCE: There has been a growing interest in depleting intracellular GSH as a potential strategy for improving ROS-based cancer therapy. Herein, a bioresponsive diselenide-functionalized dextran-based hydrogel with GPx-like catalytic activity was developed for GSH consumption-enhanced local starvation- and hypoxia-activated melanoma therapy. Results showed that the overproduced H2O2 led to accelerated intracellular GSH consumption under the cascade catalysis of small molecular selenides released from the degraded hydrogel, further enhancing the curative effect of in situ H2O2 and subsequent multimodal cancer treatment.
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  • 文章类型: Journal Article
    可持续和精确的防御工事做法对于确保日益增长的人口的粮食安全是必要的。精准农业旨在通过开发用于实际农业实践的智能材料来最大限度地减少化肥和农药的使用。这里,我们表明,在田间试验中,可以有效地利用仿生矿化来包封和可控地释放植物生物刺激剂(MiZax-3),以提高辣椒(Capsicumannum)作物的质量和产量。在现场条件下,ZIF-8封装MiZax-3(MiZIF)可以显着提高其稳定性约679倍(6p值=0.0072)。我们的结果表明,配位锌离子和MiZax-3在提高生产水果中锌含量2倍中起着至关重要的作用,这是关于水果中锌含量的这种性质的第一份报告。我们将此平台视为研究精准农业中其他基于生物相容性协调的微量营养素输送平台的起点。
    Sustainable and precise fortification practices are necessary to ensure food security for the increasing human population. Precision agriculture aims to minimize the use of fertilizers and pesticides by developing smart materials for real-life agricultural practices. Here, we show that biomimetic mineralization can be efficiently employed to encapsulate and controllably release plant biostimulants (MiZax-3) to improve the quality and yield of capsicum (Capsicum annum) crops in field experiments. ZIF-8 encapsulation of MiZax-3 (MiZIFs) could significantly enhance its stability up to around 679 times (6p value = 0.0072) at field conditions. Our results demonstrate that the coordinating Zn ions and the MiZax-3 play a vital role in improving Zn content in the produced fruits by 2-fold, which is the first report of this nature on Zn content in fruits. We envision this platform as a starting point to investigate other biocompatible coordination-based platforms for micronutrient delivery in precision agriculture.
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