nanogels

纳米凝胶
  • 文章类型: Journal Article
    由于人类病原菌的生物膜形成能力,尿路感染(UTI)的管理是一个极具挑战性的过程。这里,我们设计制造一种有效的纳米凝胶与壳聚糖生物聚合物和萘啶酸的组合,以防止形成生物膜的细菌病原体。壳聚糖包被的萘啶酸纳米凝胶(NA@CS)对细菌菌株具有出色的抑制潜力。体外,抗菌分析方法(井扩散,集落形成试验,和抗生物膜测定)进行研究制备的纳米凝胶的细菌抑制潜力,这表明NA@CS纳米凝胶对所选病原体具有更大的抑制潜力。萘啶酸与壳聚糖生物聚合物的组合由于其膜磷脂渗透的能力而降低了生物膜形成病原体的毒力和致病性。此外,制备的NA@CS纳米凝胶对L929成纤维细胞具有可靠的体外生物相容性,并与盐藻动物模型具有体内相容性。总的来说,结果表明,NA@CS纳米凝胶可有效治疗尿路感染和膀胱伤口愈合。
    Management of urinary tract infections (UTI) is a highly challenging process due to the biofilm-forming ability of human-pathogenic bacteria. Here, we designed to fabricate an effective nanogel with a combination of chitosan bio-polymer and nalidixic acid to prevent biofilm-forming bacterial pathogens. Chitosan-coated nalidixic acid nanogel (NA@CS) exhibits outstanding inhibition potential against bacterial strains. In vitro, anti-bacterial analysis methods (well diffusion, colony-forming assay, and anti-biofilm assay) were performed to study the bacterial inhibition potential of prepared nanogel, which reveals that NA@CS nanogel have greater inhibition potential against selected pathogens. The combination of nalidixic acid with chitosan biopolymer decreases the virulence and pathogenicity of biofilm-forming pathogens due to their ability to membrane phospholipids penetration. Furthermore, the fabricated NA@CS nanogel showed reliable in vitro bio-compatibility on L929 fibroblast cells and in vivo compatibility with Artemia salina animal model. Overall, the results demonstrate that NA@CS nanogel could be an effective therapeutic for treating urinary tract infections and urine bladder wound healing.
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  • 文章类型: Journal Article
    类风湿性关节炎(RA)涉及慢性炎症,氧化应激,和复杂的免疫细胞相互作用,导致联合破坏。传统治疗通常受到脱靶效应和全身毒性的限制。这项研究介绍了一种新的治疗方法,使用透明质酸(HA)-缀合,氧化还原响应型聚氨基酸纳米凝胶(HA-NG),可将他克莫司(TAC)专门用于发炎的关节。纳米凝胶的二硫键能够控制TAC释放,以响应活化巨噬细胞中的高细胞内谷胱甘肽(GSH)水平,在受RA影响的组织中普遍存在。体外结果表明,HA-NG/TAC显着降低了TAC对正常巨噬细胞的毒性,并显示出高的生物相容性。在体内,与非靶向NG/TAC相比,HA-NG/TAC在发炎的关节中积累更多,提高疗效和减少副作用。胶原诱导性关节炎(CIA)小鼠的治疗性评估显示HA-NG/TAC大大减少了爪肿胀,关节炎评分,滑膜炎症,和骨侵蚀,同时抑制促炎细胞因子水平。这些发现表明HA-NG/TAC代表了一种有前途的RA靶向药物递送系统,为更有效和更安全的临床应用提供潜力。
    Rheumatoid arthritis (RA) involves chronic inflammation, oxidative stress, and complex immune cell interactions, leading to joint destruction. Traditional treatments are often limited by off-target effects and systemic toxicity. This study introduces a novel therapeutic approach using hyaluronic acid (HA)-conjugated, redox-responsive polyamino acid nanogels (HA-NG) to deliver tacrolimus (TAC) specifically to inflamed joints. The nanogels\' disulfide bonds enable controlled TAC release in response to high intracellular glutathione (GSH) levels in activated macrophages, prevalent in RA-affected tissues. In vitro results demonstrated that HA-NG/TAC significantly reduced TAC toxicity to normal macrophages and showed high biocompatibility. In vivo, HA-NG/TAC accumulated more in inflamed joints compared to non-targeted NG/TAC, enhancing therapeutic efficacy and minimizing side effects. Therapeutic evaluation in collagen-induced arthritis (CIA) mice revealed HA-NG/TAC substantially reduced paw swelling, arthritis scores, synovial inflammation, and bone erosion while suppressing pro-inflammatory cytokine levels. These findings suggest that HA-NG/TAC represents a promising targeted drug delivery system for RA, offering potential for more effective and safer clinical applications.
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  • 文章类型: Journal Article
    各向异性金纳米粒子(AuNP)以其独特的特性而闻名-包括局部表面等离子体共振(LSPR)和对曝光的可调光学响应-能够将光转化为热,并使其成为癌症治疗的有希望的工具。尽管如此,它们倾向于聚集并因此在延长的辐照期间失去其光热转换能力,这是开发用于临床的各向异性AuNP的主要挑战。为了克服这个问题,一种创新的方法,促进单个各向异性AuNP在薄纳米凝胶内的封装,形成混合纳米材料,反映无机核心的形态,同时引入一个可忽略的(2-8nm)增加的总直径提出。成功证明了棒状和星形各向异性AuNP在聚丙烯酰胺(pAA)或聚(N-异丙基丙烯酰胺)(pNIPAM)纳米凝胶中的封装。超薄聚合物层显示出非凡的耐久性,显着增强各向异性AuNP与近红外光相互作用期间的光热稳定性,并有效地提高其光热能力延长辐照期。因此,研究结果支持开发更稳定和可靠的AuNPs作为混合纳米材料,将它们定位为有前途的纳米医学平台。
    Anisotropic gold nanoparticles (AuNPs) are renowned for their unique properties - including localized surface plasmon resonance (LSPR) and adjustable optical responses to light exposure - that enable the conversion of light into heat and make them a promising tool in cancer therapy. Nonetheless, their tendency to aggregate and consequently lose their photothermal conversion capacity during prolonged irradiation periods represents a central challenge in developing anisotropic AuNPs for clinical use. To overcome this issue, an innovative approach that facilitates the encapsulation of individual anisotropic AuNPs within thin nanogels, forming hybrid nanomaterials that mirror the inorganic core\'s morphology while introducing a negligible (2-8 nm) increase in overall diameter is proposed. The encapsulation of rod- and star-shaped anisotropic AuNPs within poly-acrylamide (pAA) or poly-(N-isopropylacrylamide) (pNIPAM) nanogels is successfully demonstrated. The ultrathin polymeric layers display remarkable durability, significantly enhancing the photothermal stability of anisotropic AuNPs during their interaction with near-infrared light and effectively boosting their photothermal capacities for extended irradiation periods. The outcomes of the research thus support the development of more stable and reliable AuNPs as hybrid nanomaterials, positioning them as promising nanomedicinal platforms.
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  • 文章类型: Journal Article
    标准铂类化疗与EGFR酪氨酸激酶抑制剂吉非替尼(Gef)的联合主要通过非重叠作用机制提高晚期非小细胞肺癌(NSCLC)的抗癌疗效。然而,顺铂(Cis)和Gef联合应用的临床试验未能显示治疗改善,可能是由于Gef干扰导致Cis的细胞流入受损.为了克服Cis和Gef在抗NSCLC治疗中的拮抗作用,在这里,我们展示了一种自靶向透明质酸(HA)纳米凝胶,通过利用HA固有靶向CD44(一种在肺癌细胞上经常过表达的受体)来促进抗癌共递送.HA之间的共同组装,Cis和Gef产生177.8nm的HA/Cis/Gef纳米凝胶,具有延长的药物释放。与Gef抑制顺式摄取不同,HA/Cis/Gef纳米凝胶通过CD44靶向递送有效促进药物内化,如在H1975NSCLC模型中体外和体内HA竞争和CD44敲低所证实.此外,结合游离Cis和Gef,HA/Cis/Gef纳米凝胶显著提高了抗癌功效,同时减少了副作用。这种CD44靶向的HA/Cis/Gef纳米凝胶提供了一种有效的策略,将基于铂的联合治疗推向优化的NSCLC治疗。
    The combination of the standard platinum-based chemotherapy with EGFR-tyrosine kinase inhibitor Gefitinib (Gef) principally boosts the anticancer efficacy of advanced non-small cell lung cancer (NSCLC) through non-overlapping mechanisms of action, however the clinical trials of cisplatin (Cis) and Gef combination failed to show a therapeutic improvement likely due to compromised cellular influx of Cis with the Gef interference. To overcome the antagonism between Cis and Gef in anti-NSCLC therapy, here we demonstrated a self-targeted hyaluronan (HA) nanogel to facilitate the anticancer co-delivery by utilizing the HA\'s intrinsic targeting towards CD44, a receptor frequently overexpressed on lung cancer cells. The co-assembly between HA, Cis and Gef generated a HA/Cis/Gef nanogel of 177.8 nm, featuring a prolonged drug release. Unlike the Gef inhibited the Cis uptake, the HA/Cis/Gef nanogel efficiently facilitated the drug internalization through CD44-targeted delivery as verified by HA competition and CD44 knocking down in H1975 NSCLC model both in vitro and in vivo. Moreover, the HA/Cis/Gef nanogel significantly improved the anticancer efficacy and meanwhile diminished the side effects in reference to the combination of free Cis and Gef. This CD44-targeted HA/Cis/Gef nanogel provided a potent strategy to advance the platinum-based combination therapy towards optimized NSCLC therapy.
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  • 文章类型: Journal Article
    由于粘膜屏障的综合障碍,有效的药物递送到细菌感染的粘膜仍然是一个挑战。pH值变化,和高浓度的谷胱甘肽.然而,基于多糖的响应性纳米凝胶(NG)可以利用这些条件来递送特定的抗微生物剂。我们探索了pH和氧化还原响应性NG的关键特征,以增加药物渗透,停留时间,和感染粘膜的功效。我们使用羟丙基纤维素作为模板制备了多功能NG,用于甲基丙烯酸与N,N'-双(丙烯酰基)胱胺(BAC)或N,N'-亚甲基双(丙烯酰胺)(BIS)。NG-粘蛋白结合和负载多西环素的NG的抗菌功效的研究揭示了对pH的响应和氧化还原线索之间的相互作用。具体来说,较高的BAC组合物在还原条件下增加粘液结合和控制释放,而较高的BIS组合物产生的NG具有较高的强力霉素介导的对金黄色葡萄球菌的抗菌功效。研究结果揭示了多反应性NG在感染粘膜中有效的抗微生物剂递送中的潜力。
    Effective drug delivery to bacterially infected mucosa remains a challenge due to the combined obstacles of the mucosal barrier, pH variations, and high concentrations of glutathione. However, polysaccharide-based responsive nanogels (NGs) can take advantage of these conditions to deliver specific antimicrobials. We explored the critical features of pH- and redox-responsive NGs to increase drug penetration, residence time, and efficacy in the infected mucosa. We prepared multifunctional NGs using hydroxypropyl cellulose as a template for the cross-linking of methacrylic acid with N,N\'-bis(acryloyl)cystamine (BAC) or N,N\'-methylenebis(acrylamide) (BIS). Studies of NG-mucin binding and the antibacterial efficacy of doxycycline-loaded NGs revealed the interplay between the response to pH and redox clues. Specifically, higher BAC composition increased mucus binding and controlled release in reductive conditions, while higher BIS composition yielded NGs with higher doxycycline-mediated antibacterial efficacy against Staphylococcus aureus. The findings reveal the potential of multiresponsive NGs in effective antimicrobial delivery in infected mucosa.
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  • 文章类型: Journal Article
    目的:在本研究中,我们尝试使用小鼠腹裂模型在生物片上使用纳米凝胶支架创建由直接转化的成肌细胞(dMB)制成的骨骼肌片。
    方法:通过将MYOD1和MYCL共转染到人成纤维细胞中来制备dMB。将硅管植入NOG/SCID小鼠的皮肤下,并形成生物薄片。纳米凝胶是一种基于胆固醇改性普鲁兰的纳米级水凝胶,通过冷冻干燥纳米凝胶制备NanoClip-FD凝胶。7mm长的NOG/SCID小鼠腹壁造就为小鼠腹裂模子。将接种有dMB的Matrigel或NanoCliP-FD凝胶放置在生物片上并植入模型小鼠上。
    结果:手术后14天,带有Matrigel的dMB显示出少量的肌肉样细胞的粗聚集。相比之下,dMB与NanoCliP-FD凝胶显示多核肌样细胞,通过荧光免疫染色表达为结蛋白和肌原蛋白。
    结论:纳米凝胶具有多孔结构,通过向细胞提供氧气和营养物质,可用作组织再生的支架。结合dMB和纳米凝胶的生物片导致分化和移植的骨骼肌,这表明有可能形成源自自体细胞和组织的骨骼肌片。
    OBJECTIVE: In this study, we attempted to create skeletal muscle sheets made of directly converted myoblasts (dMBs) with a nanogel scaffold on a biosheet using a mouse gastroschisis model.
    METHODS: dMBs were prepared by the co-transfection of MYOD1 and MYCL into human fibroblasts. Silicon tubes were implanted under the skin of NOG/SCID mice, and biosheets were formed. The nanogel was a nanoscale hydrogel based on cholesterol-modified pullulan, and a NanoClip-FD gel was prepared by freeze-drying the nanogel. 7 mm in length was created in the abdominal wall of NOG/SCID mice as a mouse gastroschisis model. Matrigel or NanoCliP-FD gel seeded with dMBs was placed on the biosheet and implanted on the model mice.
    RESULTS: Fourteen days after surgery, dMBs with Matrigel showed a small amount of coarse aggregations of muscle-like cells. In contrast, dMBs with NanoCliP-FD gel showed multinucleated muscle-like cells, which were expressed as desmin and myogenin by fluorescent immunostaining.
    CONCLUSIONS: Nanogels have a porous structure and are useful as scaffolds for tissue regeneration by supplying oxygen and nutrients supply to the cells. Combining dMBs and nanogels on the biosheets resulted in the differentiation and engraftment of skeletal muscle, suggesting the possibility of developing skeletal muscle sheets derived from autologous cells and tissues.
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  • 文章类型: Journal Article
    三硝基甘油(TNG)具有显着的血管生成,抗菌,和抗氧化活性是控制伤口愈合能力的有希望的候选者。然而,由于相关并发症和半衰期短,其临床给药受到限制。在目前的研究中,在体外和体内检查了负载TNG的壳聚糖纳米凝胶(TNG-Ngs),以了解其临床应用。我们制备了TNG-Ngs并表征了它们的理化性质。使用生物相容性评估了TNG-Ngs的潜力,划痕试验,和全厚度皮肤伤口模型,随后进行组织病理学和免疫组织化学检查。TNG-Ngs粒径96±18和确定的尺寸分布直方图。制备的TNG-Ngs的负载能力(LC)和封装效率(EE)分别为70.2%和2.1%,分别。TNG-Ngs样品显示增强的HUVEC迁移,没有明显的细胞毒性。在伤口上局部使用TNG-Ngs200显示完全的伤口闭合率,皮肤成分形成,疤痕宽度较小,显著的肉芽组织,促进胶原蛋白沉积,并提高了α-SMA和CD31的相对平均密度。TNG-Ngs通过促进胶原沉积和血管生成活性加速伤口愈合,以及减少炎症。研究结果表明,TNG-Ngs有望在伤口区域血管化良好,并在局部治疗中更有效。
    Trinitroglycerin (TNG) with remarkable angiogenic, antibacterial, and antioxidative activity is a promising candidate to govern wound healing capacity. However, its clinical administration is limited due to associated complications and NO short half-life. In the current study, TNG-loaded chitosan nanogels (TNG-Ngs) were examined in-vitro and in-vivo to gain insight into their clinical application. We prepared TNG-Ngs and characterized their physiochemical properties. The potential of TNG-Ngs was assessed using biocompatibility, scratch assay, and a full-thickness skin wounds model, followed by histopathological and immunohistochemistry examinations. TNG-Ngs particle size 96 ± 18 and definite size distribution histogram. The loading capacity (LC) and encapsulation efficiency (EE) of prepared TNG-Ngs were 70.2 % and 2.1 %, respectively. The TNG-Ngs samples showed enhanced migration of HUVECs with no apparent cytotoxicity. The topical use of TNG-Ngs200 on the wounds revealed a complete wound closure ratio, skin component formation, less scar width, remarkable granulation tissue, promoted collagen deposition, and enhanced the relative mean density of α-SMA and CD31. TNG-Ngs accelerated wound healing by promoting collagen deposition and angiogenic activity, as well as reducing inflammation. The findings indicated that TNG-Ngs is expected to be well vascularized in the wound area and to be more effective in topical therapy.
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  • 文章类型: Journal Article
    具有双电和光输出的光子离子凝胶已经被深入研究。然而,由热敏纳米凝胶组装的可调谐温度响应光子离子凝胶尚未被研究。在这里,一种制造光子离子凝胶的创新方法已经被开发用于具有可调温度灵敏度和结构颜色的智能可穿戴设备。首先,聚(异丙基丙烯酰胺-r-苯基马来苯胺酸)P(NIPAm-r-NPMA)纳米凝胶在丙烯酸2-羟乙酯(HEA)中自组装成光子晶体,水,和三氟甲磺酸1-乙基-3-甲基咪唑鎓的离子液体。然后通过聚(乙二醇)二丙烯酸酯(PEGDA)交联的丙烯酸2-羟乙酯的聚合来开发强大的光子离子凝胶。离子液体的掺入,三氟甲磺酸1-乙基-3-甲基咪唑,增强光子离子凝胶的机械强度,调整离子凝胶的温度敏感性,使它们适应各种环境条件。研究结果表明,这些离子凝胶可以在智能可穿戴设备中提供双重功能,由于离子液体的导电性和来自纳米凝胶组件的结构颜色,组合电和光信号输出。所得到的光子离子凝胶表现出优异的基材附着力,机械稳定性,和快速的弹性。更重要的是,这些离子凝胶中的纳米凝胶充当光子晶体(PC)的构建块,赋予了与角度无关的着色,并增强了超过200%的拉伸性,而没有纳米凝胶的离子凝胶的可拉伸性仅为约100%。我们具有可调温度灵敏度和双输出的光子离子凝胶将为创新智能可穿戴设备的开发开辟一条道路。
    Photonic ionogels with dual electrical and optical output have been intensively studied. However, tunable temperature-responsive photonic ionogel assembled by thermosensitive nanogels has not been studied yet. Herein, an innovative approach to fabricate photonic ionogels has been developed for smart wearable devices with tunable temperature sensitivity and structural color. Firstly, poly(isopropylacrylamide-r-phenylmaleanilic acid) P(NIPAm-r-NPMA) nanogels self-assemble into photonic crystals in 2-hydroxyethyl acrylate (HEA), water, and the ionic liquid of 1-ethyl-3-methylimidazolium trifluoromethanesulfonate. And then robust photonic ionogels are developed through a polymerization of 2-hydroxyethyl acrylate crosslinked by poly(ethylene glycol) diacrylate (PEGDA). The incorporation of the ionic liquid, 1-ethyl-3-methylimidazolium trifluoromethanesulfonate, enhances the mechanical strength of photonic ionogels and tunes the temperature-sensitivity of the ionogels, making them adaptable to various environmental conditions. The findings demonstrate that these ionogels can serve dual functions in smart wearable devices, combining electrical and optical signal outputs due to the conductivity of the ionic liquid and structural color from the nanogel assembly. The resultant photonic ionogels exhibit exceptional substrate adhesion, mechanical stability, and fast resilience. More significantly, the nanogels within these ionogels serve as the building blocks of photonic crystals (PCs) endow with angle-independent coloration and enhance stretchability beyond 200 %, while the stretchability of the ionogles without the nanogels is only about 100 %. Our photonic ionogels with tunable temperature-sensitivity and dual outputs will open an avenue to the development of the innovative smart wearable devices.
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  • 文章类型: Journal Article
    通过介观计算机模拟研究了响应性纳米凝胶在平面脂质双层上的溶胀和塌陷。分子量的影响,交联密度,并检查粘合强度。发现了由双层介导的塌陷吞噬的条件。特别是,结果表明,在低疏水性水平下,纳米凝胶柔软度的增加降低了吞噬速率。相反,对于更强的疏水性水平,趋势向相反的方向变化。同时,当交联密度太低或粘合强度太高时,膜处的纳米凝胶变形抑制吞噬,而与网络溶胀率无关。最后,出于比较原因,纳米凝胶的行为也在固体表面进行了研究。这些结果可用于设计能够调节其弹性和孔隙率以成功进行细胞内药物递送的软颗粒。
    The swelling and collapse of responsive nanogels on a planar lipid bilayer are studied by means of mesoscopic computer simulations. The effects of molecular weight, cross-linking density, and adhesion strength are examined. The conditions for collapse-mediated engulfing by the bilayer are found. In particular, the results show that at low hydrophobicity level the increase in the nanogel softness decreases the engulfing rate. On the contrary, for stronger hydrophobicity level the trend changes to the opposite one. At the same time, when the cross-linking density is too low or the adhesion strength is too high the nanogel deformation at the membrane suppresses the engulfing regardless of the network swelling ratio. Finally, for comparative reasons, the behavior of the nanogels is also studied at the solid surface. These results may be useful in the design of soft particles capable of tuning of their elasticity and porosity for successful intracellular drug delivery.
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  • 文章类型: Journal Article
    纳米医学已经成为推进癌症治疗的一个有希望的途径,但是减轻其体内副作用的挑战需要开发创新的结构和材料。最近的调查揭示了纳米凝胶作为特别引人注目的候选人,以多孔为特征,三维网络结构,表现出卓越的药物装载能力。除此之外,纳米凝胶具有相当大的比表面积,可以用特定的化学官能团定制。因此,纳米凝胶经常被设计为对抗癌症的多模式协同平台,其中光热疗法由于其穿透深层组织并通过应用升高的温度实现局部肿瘤根除的能力而脱颖而出。在这次审查中,我们深入研究了各种光热纳米凝胶的合成,这些纳米凝胶能够通过化学或物理刺激来控制药物的释放。它还总结了它们与光热疗法以及其他治疗方式协同整合以实现有效的肿瘤消融的潜力。此外,我们分析了光热纳米凝胶对癌症治疗贡献的主要机制,同时强调了它们在调节治疗温度以修复由肿瘤相关创伤引起的骨缺损方面的能力.被视为癌症治疗领域的吉祥策略,光热纳米凝胶有望提供受控的药物输送和精确的热消融能力。
    Nanomedicine has emerged as a promising avenue for advancing cancer treatment, but the challenge of mitigating its in vivo side effects necessitates the development of innovative structures and materials. Recent investigation has unveiled nanogels as particularly compelling candidates, characterized by a porous, three-dimensional network architecture that exhibits exceptional drug loading capacity. Beyond this, nanogels boast a substantial specific surface area and can be tailored with specific chemical functionalities. Consequently, nanogels are frequently engineered as a multi-modal synergistic platform for combating cancer, wherein photothermal therapy stands out due to its capacity to penetrate deep tissues and achieve localized tumor eradication through the application of elevated temperatures. In this review, we delve into the synthesis of diverse varieties of photothermal nanogels capable of controlled drug release triggered by either chemical or physical stimuli. It also summarizes their potential for synergistic integration with photothermal therapy alongside other therapeutic modalities to realize effective tumor ablation. Moreover, we analyze the primary mechanisms underlying the contribution of photothermal nanogels to cancer treatment while underscoring their adeptness in regulating therapeutic temperatures for repairing bone defects resulting from tumor-associated trauma. Envisioned as an auspicious strategy in the realm of cancer therapy, photothermal nanogels hold promise for furnishing controlled drug delivery and precise thermal ablation capabilities.
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