Liposome

脂质体
  • 文章类型: Journal Article
    迫切需要从饮用水中去除全氟烷基物质和多氟烷基物质(PFAS)。这里,我们证明了囊泡对PFAS吸附的高性能。本研究中使用的囊泡是封闭的两亲性双层,将其疏水基团保持在水中,亲水基团保持在水中。全氟辛烷磺酸(PFOS)在囊泡中的分配系数Kd为5.3×105L/kg,高于颗粒状活性炭(GAC),用于囊泡的全氟辛酸(PFOA)的Kd为103-104L/kg。DMPC囊泡对PFOA和PFOS吸附的去除效率分别为97.1±0.1%和99.4±0.2%,分别。通过改变囊泡组分疏水链中顺式双键的数量,研究了PFOA和PFOS在囊泡上的吸附行为。此外,还测试了由不同相的膜形成的囊泡。结果显示,当囊泡由液晶(类液体)相的膜形成时,随着烃链中顺式双键的减少,PFOA和PFOS的吸附量都增加,这被认为是由于分子形状相似性。当囊泡由凝胶(固体状)相中的膜形成时,它们不像在液晶相中那样吸附PFAS,即使烃链没有任何顺式双键。我们的发现表明,通过优化囊泡成分的结构及其热力学相,囊泡可以用作PFAS吸附剂。的确,囊泡(DMPC)被证明可以吸附PFOA和PFOS,甚至在环境水中也被凝结剂凝结。该凝结将使得能够在吸附后从水中去除PFOA和PFOS。
    The removal of per- and polyfluoroalkyl substances (PFAS) from drinking water is urgently needed. Here, we demonstrated high performance of vesicles on PFAS adsorption. Vesicles used in this study were enclosed amphiphile bilayers keeping their hydrophobic groups inside and their hydrophilic groups outside in water. The distribution coefficient Kd of perfluorooctane sulfonic acid (PFOS) for vesicles was 5.3 × 105 L/kg, which is higher than that for granulated activated carbon (GAC), and Kd of perfluorooctanoic acid (PFOA) for vesicles was 103-104 L/kg. The removal efficiencies of PFOA and PFOS adsorption on DMPC vesicles were 97.1 ± 0.1% and 99.4 ± 0.2%, respectively. The adsorption behaviors of PFOA and PFOS on vesicles were investigated by changing the number of cis-double bonds in the hydrophobic chains of the vesicle constituents. Moreover, vesicles formed by membranes in the different phases were also tested. The results revealed that, when vesicles are formed of a membrane in the liquid-crystalline (liquid-like) phase, the adsorption amounts of both PFOA and PFOS increased as the cis-double bond in the hydrocarbon chains decreased, which is considered due to molecular shape similarity. When vesicles are formed of a membrane in the gel (solid-like) phase, they do not adsorb PFAS as much as in the liquid-crystalline phase, even though the hydrocarbon chains do not have any cis-double bond. Our findings demonstrate that vesicles can be utilized as PFAS adsorbents by optimizing the structure of vesicle constituents and their thermodynamical phase. Indeed, the vesicles (DMPC) were demonstrated that they can adsorb PFOA and PFOS, and be coagulated by a coagulant even in environmental water. The coagulation will enable the removal of PFOA and PFOS from the water after adsorption.
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  • 文章类型: Journal Article
    构建具有双配体的新型纳米载体,以实现优异的抗肿瘤功效和较低的毒副作用。
    采用薄膜水化法制备脂质体。紫外线,高效液相色谱法,纳米尺寸分析仪,超滤离心,透析,透射电子显微镜,流式细胞术,细胞计数试剂盒-8,共聚焦激光扫描显微镜,transwell,和肿瘤球体测定法用于研究其特征,细胞毒性,和体外靶向dg-Bcan靶向肽(BTP-7)/pHA-替莫唑胺(TMZ)/四(4-羧基苯基)卟啉(TCPP)-Lip。
    BTP-7/pHA-TMZ/TCPP-Lip是一个球体,平均直径为143±3.214nm,多分散指数为0.203±0.025,表面电荷为-22.8±0.425mV。载药量(TMZ和TCPP)为7.40±0.23%和2.05±0.03%(mg/mg);包封效率为81.43±0.51%和84.28±1.64%(mg/mg)。结果表明,BTP-7/pHA-TMZ/TCPP-Lip具有增强的靶向性和细胞毒性。
    BTP-7/pHA-TMZ/TCPP-Lip可以特异性靶向肿瘤细胞,实现高效的药物输送,提高抗肿瘤疗效,降低全身毒性。
    UNASSIGNED: To construct a novel nano-carrier with dual ligands to achieve superior anti-tumour efficacy and lower toxic side effects.
    UNASSIGNED: Liposomes were prepared by thin film hydration method. Ultraviolet, high performance liquid chromatography, nano-size analyser, ultrafiltration centrifugation, dialysis, transmission electron microscope, flow cytometry, Cell Counting Kit-8, confocal laser scanning microscopy, transwell, and tumorsphere assay were used to study the characterisations, cytotoxicity, and in vitro targeting of dg-Bcan targeting peptide (BTP-7)/pHA-temozolomide (TMZ)/tetra(4-carboxyphenyl)porphyrin (TCPP)-Lip.
    UNASSIGNED: BTP-7/pHA-TMZ/TCPP-Lip was a spheroid with a mean diameters of 143 ± 3.214 nm, a polydispersity index of 0.203 ± 0.025 and a surface charge of -22.8 ± 0.425 mV. The drug loadings (TMZ and TCPP) are 7.40 ± 0.23% and 2.05 ± 0.03% (mg/mg); and the encapsulation efficiencies are 81.43 ± 0.51% and 84.28 ± 1.64% (mg/mg). The results showed that BTP-7/pHA-TMZ/TCPP-Lip presented enhanced targeting and cytotoxicity.
    UNASSIGNED: BTP-7/pHA-TMZ/TCPP-Lip can specifically target the tumour cells to achieve efficient drug delivery, and improve the anti-tumour efficacy and reduces the systemic toxicity.
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  • 文章类型: Journal Article
    已经提出了多种奥沙利铂耐药机制,例如抗炎M2巨噬细胞的增加和细胞毒性T细胞的缺乏。从而奥沙利铂化疗促进免疫抑制肿瘤微环境并抑制抗肿瘤功效。研究表明,toll样受体(TLR)激动剂能够引发广泛的炎症反应,这可能会降低奥沙利铂耐药并提高化疗疗效。在这项研究中,我们建立了结直肠荷瘤斑马鱼和小鼠,并研究了TLR激动剂和奥沙利铂在体内巨噬细胞功能和抗肿瘤T细胞免疫以及肿瘤生长控制中的作用。为了增加这种策略的潜力,同时尽量减少副作用,携带奥沙利铂的中性脂质体和共负载有TLR激动剂的阳离子脂质体聚I:C和R848用于最大免疫激活。两种脂质体系统均表现出良好的理化性质和优异的体外生物活性。通过脂质体递送的组合策略显示出更明显的肿瘤消退,并且与斑马鱼和小鼠的M2巨噬细胞数量减少相关。越来越多的树突状细胞,在处理的小鼠中观察到由免疫原性细胞死亡介导的DC成熟和T细胞浸润。我们的研究为脂质体联合治疗通过重新编程肿瘤微环境和增强免疫反应来改善癌症治疗的潜力提供了有价值的见解。
    Multiple oxaliplatin-resistance mechanisms have been proposed such as increase of anti-inflammatory M2 macrophages and lack of cytotoxic T-cells. Thereby oxaliplatin chemotherapy promotes an immunosuppressive tumor microenvironment and inhibits anti-tumor efficacy. It has been shown that toll-like receptor (TLR) agonists are capable of triggering broad inflammatory responses, which may potentially reduce oxaliplatin-resistance and improve the efficacy of chemotherapy. In this study, we established colorectal tumor-bearing zebrafish and mice, and investigated the effects of TLR agonists and oxaliplatin in macrophage function and anti-tumor T cell immunity as well as tumor growth control in vivo. To increase the potential of this strategy as well minimize side effects, neutral liposomes carrying oxaliplatin and cationic liposomes co-loaded with TLR agonists Poly I:C and R848 were employed for maximum immune activation. Both of two liposomal systems exhibited good physicochemical properties and excellent biological activities in vitro. The combination strategy delivered by liposomes showed more pronounced tumor regression and correlated with decreased M2 macrophage numbers in both zebrafish and mice. Increasing numbers of dendritic cells, DC maturation and T cell infiltration mediated via immunogenic cell death were observed in treated mice. Our study offers valuable insights into the potential of liposomal combination therapy to improve cancer treatment by reprogramming the tumor microenvironment and enhancing immune responses.
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  • 文章类型: Journal Article
    胶质瘤是中枢神经体系的原发性恶性肿瘤。近年来,神经胶质瘤的治疗发展迅速,但胶质瘤患者的总体生存率并没有明显改善。由于血脑屏障和颅内肿瘤屏障的存在,许多在体外治疗胶质瘤效果良好的药物不能准确转运到相应的病灶。为了使抗肿瘤药物克服障碍,靶向胶质瘤,纳米药物递送系统最近出现。令人欣慰的是,脂质体,作为一种多功能的纳米药物载体,可以与亲水和疏水药物相容,容易被各种靶向配体官能化,可生物降解,体内免疫原性低,已成为解决神经胶质瘤用药棘手问题的质量选择。因此,我们专注于脂质体纳米药物递送系统,并对其目前在胶质瘤中的研究进展进行了综述。希望,本综述可能为临床治疗胶质瘤的脂质体纳米材料的研发提供新的思路。
    Glioma is a primary malignant tumor in the central nervous system. In recent years, the treatment of glioma has developed rapidly, but the overall survival of glioma patients has not significantly improved. Due to the presence of the blood-brain barrier and intracranial tumor barrier, many drugs with good effects to cure glioma in vitro cannot be accurately transported to the corresponding lesions. In order to enable anti-tumor drugs to overcome the barriers and target glioma, nanodrug delivery systems have emerged recently. It is gratifying that liposomes, as a multifunctional nanodrug delivery carrier, which can be compatible with hydrophilic and hydrophobic drugs, easily functionalized by various targeted ligands, biodegradable, and hypoimmunogenic in vivo, has become a quality choice to solve the intractable problem of glioma medication. Therefore, we focused on the liposome nanodrug delivery system, and summarized its current research progress in glioma. Hopefully, this review may provide new ideas for the research and development of liposome-based nanomaterials for the clinical treatment of glioma.
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  • 文章类型: Journal Article
    为了研究脂质体泼尼松龙磷酸盐在小型猪PVR模型中减轻增殖性玻璃体视网膜病变(PVR)严重程度的功效。
    共有18只眼的9只小型猪接受了手术诱导PVR。眼睛被随机分为三组:玻璃体内注射脂质体磷酸泼尼松龙(LPP),曲安奈德(TA),和控制。使用改良版本的硅研究分类系统在眼底镜检查上对PVR严重程度进行分级。重度PVR在此分类中被定义为2-5级,重度PVR视网膜脱离的比例,定义为视网膜再脱离,即,在治疗组和对照组之间比较PVR2-5级。
    在第28天,观察到对照组中的5只眼睛(83.3%)具有严重的PVR。在LPP组中,1只(16.7%)眼因重度PVR出现视网膜脱离。在四只(66.7%)眼睛中观察到0级PVR,一级(16.7%)眼睛,一只眼睛(16.7%)为5级。在TA组中,在四只眼睛中观察到0级PVR(66.7%),两只眼睛一年级(16.6%),一只眼睛(16.7%)为5级。在第28天,与对照组相比,LPP组严重PVR的眼睛比例差异显着降低(16.7%vs83.3%,p=0.02)。脂质体磷酸泼尼松龙和曲安奈德组之间的严重PVR率或中位PVR等级没有显着差异。
    脂质体磷酸泼尼松龙降低了PVR的小型猪模型中PVR的严重程度。
    UNASSIGNED: To investigate the efficacy of liposomal prednisolone phosphate to mitigate the severity of proliferative vitreoretinopathy (PVR) in a minipig model of PVR.
    UNASSIGNED: A total of 18 eyes of 9 minipigs underwent PVR induction surgically. Eyes were randomized equally into three groups: intravitreal injection of liposomal prednisolone phosphate (LPP), triamcinolone acetonide (TA), and controls. PVR severity was graded on fundoscopic examination using a modified version of the Silicon Study Classification System. Severe PVR was defined as grade 2-5 on this classification, and the proportion of eyes with retinal detachment from severe PVR, defined as retinal re-detachment, i.e., PVR grade 2-5, was compared between treatment and control groups.
    UNASSIGNED: On day 28, five eyes (83.3%) in the control group were observed to have severe PVR. Within the LPP group, one (16.7%) eye developed retinal detachment due to severe PVR. Grade 0 PVR was observed in four (66.7%) eyes, grade 1 in one (16.7%) eye, and grade 5 in one (16.7%) eye. Within the TA group, grade 0 PVR was observed in four eyes (66.7%), grade 1 in two eyes (16.6%), and grade 5 in one (16.7%) eye. The difference in the proportion of eyes with severe PVR was significantly lower in the LPP group compared to controls at day 28 (16.7% vs 83.3%, p=0.02). There was no significant difference in the rate of severe PVR or median PVR grade between the liposomal prednisolone phosphate and triamcinolone acetonide groups.
    UNASSIGNED: Liposomal prednisolone phosphate reduces the severity of PVR in a minipig model of PVR.
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  • 文章类型: Journal Article
    由于血脑屏障(BBB),脑靶向药物递送提出了巨大的挑战。在之前的研究中,我们开发了一种肽修饰的隐形脂质体(SP-sLip),通过血浆中载脂蛋白的吸附来增强BBB的渗透。SP是源自淀粉样蛋白β肽(Aβ1-42)的25至35的11个氨基酸的肽,这是载脂蛋白的天然配体。尽管SP-sLip表现出有效的脑靶向性能,自聚合和存储的不稳定性限制了其进一步的应用。在这项研究中,我们根据具有D-氨基酸的SP的反向序列开发了D-肽配体,被称为DSP,来解决问题。值得注意的是,与SP肽相比,DSP表现出降低的自聚集倾向和优异的稳定性。此外,与SP-sLip相比,DSP修饰的sLip(DSP-sLip)显示出增强的稳定性(>2周),延长血液循环(AUC增加44.4%),减少肝脏和脾脏积累(减少2.23倍和1.86倍),具有相当的脑靶向效率。类似于SP-sLip,DSP-sLip选择性吸附载脂蛋白A1,E,和J在血液中形成功能化的蛋白质电晕,从而通过载脂蛋白受体介导的胞吞作用穿过BBB。这些发现强调了配体稳定性在脑靶向脂质体的体外和体内性能中的重要性。从而为高效稳定的纳米载体的设计和优化铺平了道路。
    Brain-targeted drug delivery poses a great challenge due to the blood-brain barrier (BBB). In a previous study, we have developed a peptide-modified stealth liposome (SP-sLip) to enhance BBB penetration via the adsorption of apolipoproteins in plasma. SP is an 11-amino acid peptide derived from 25 to 35 of the Amyloid β peptide (Aβ1-42), which is the nature ligand of apolipoproteins. Although SP-sLip exhibited efficient brain targeting performance, self-aggregation and instability of storage limited its further application. In this study, we developed a D-peptide ligand according to the reverse sequence of SP with D-amino acids, known as DSP, to solve the problems. Notably, DSP exhibited a reduced tendency for self-aggregation and exceptional stability compared to the SP peptide. Furthermore, compared to SP-sLip, DSP-modified sLip (DSP-sLip) demonstrated enhanced stability (>2 weeks), prolonged blood circulation (AUC increased 44.4%), reduced liver and spleen accumulation (reduced by 2.23 times and 1.86 times) with comparable brain-targeting efficiency. Similar to SP-sLip, DSP-sLip selectively adsorbed apolipoprotein A1, E, and J in the blood to form functionalized protein corona, thus crossing BBB via apolipoprotein receptor-mediated transcytosis. These findings underscored the importance of ligand stability in the in vitro and in vivo performance of brain-targeted liposomes, therefore paving the way for the design and optimization of efficient and stable nanocarriers.
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  • 文章类型: Journal Article
    金属有机骨架(MOFs)是固定酶以构建酶@MOF复合材料并扩展生物催化剂应用的有利宿主材料。然而,MOFs的刚性结构没有可调的中空空隙和限制效应通常限制了它们的催化活性。利用智能软聚合物来克服这一限制,在这里,使用谷胱甘肽敏感的脂质体(L)作为软模板,开发了将酶包封在沸石咪唑酯骨架-8(ZIF-8)中的保护方案。首先将葡萄糖氧化酶(GOx)和辣根过氧化物酶(HRP)锚定在光响应和热响应的多孔聚(苯乙烯-马来酸酐-N,甲基丙烯酸N-二甲基氨基乙酯-螺吡喃)膜(PSMDSP)生产PSMDSP@GOx-HRP,这可以通过切换UV照射或改变温度来提供限制效果。之后,将PSMDSP@GOx-HRP嵌入L,将PSMDSP@GOx-HRP@L封装到中空ZIF-8(HZIF-8)中,形成PSMDSP@GOx-HRP@HZIF-8复合材料,在通过添加谷胱甘肽除去L后的框架结晶过程中进行。令人印象深刻的是,在47°C的紫外线照射下,复合材料的生物催化活性比游离酶的生物催化活性高4.45倍,这可能得益于PSMDSP的限制效应和HZIF-8酶的构象自由度。所提出的复合材料有助于保护酶免受苛刻条件的影响,并表现出优异的稳定性。此外,建立了基于复合物的比色测定法,用于检测血清葡萄糖,线性范围为0.05-5.0mM,在级联反应系统中计算的LOD值为0.001mM。这项工作提供了一种通用的设计思想和通用技术,可以将酶固定在可以封装在多孔刚性MOF宿主中的软聚合物膜上。它还具有开发具有可调限制效应和高催化性能的智能聚合物@酶@HMOFs生物催化剂的潜力。
    Metal-organic frameworks (MOFs) are favorable hosting materials for fixing enzymes to construct enzyme@MOF composites and to expand the applications of biocatalysts. However, the rigid structure of MOFs without tunable hollow voids and a confinement effect often limits their catalytic activities. Taking advantage of the smart soft polymers to overcome the limitation, herein, a protection protocol to encapsulate the enzyme in zeolitic imidazolate framework-8 (ZIF-8) was developed using a glutathione-sensitive liposome (L) as a soft template. Glucose oxidase (GOx) and horseradish peroxidase (HRP) were first anchored on a light- and thermoresponsive porous poly(styrene-maleic anhydride-N,N-dimethylaminoethyl methacrylate-spiropyran) membrane (PSMDSP) to produce PSMDSP@GOx-HRP, which could provide a confinement effect by switching the UV irradiation or varying the temperature. Afterward, embedding PSMDSP@GOx-HRP in L and encapsulating PSMDSP@GOx-HRP@L into hollow ZIF-8 (HZIF-8) to form PSMDSP@GOx-HRP@HZIF-8 composites were performed, which proceeded during the crystallization of the framework following the removal of L by adding glutathione. Impressively, the biocatalytic activity of the composites was 4.45-fold higher than that of the free enzyme under UV irradiation at 47 °C, which could benefit from the confinement effect of PSMDSP and the conformational freedom of the enzyme in HZIF-8. The proposed composites contributed to the protection of the enzyme against harsh conditions and exhibited superior stability. Furthermore, a colorimetric assay based on the composites for the detection of serum glucose was established with a linearity range of 0.05-5.0 mM, and the calculated LOD value was 0.001 mM in a cascade reaction system. This work provides a universal design idea and a versatile technique to immobilize enzymes on soft polymer membranes that can be encapsulated in porous rigid MOF-hosts. It also holds potential for the development of smart polymer@enzyme@HMOFs biocatalysts with a tunable confinement effect and high catalytic performance.
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  • 文章类型: Journal Article
    T细胞受体(TCR)工程T细胞治疗,与嵌合抗原受体T细胞疗法不同,依赖于TCR检测更广泛的抗原表位的固有能力,例如在细胞内部或外部发现的蛋白质片段。因此,TCR-T细胞疗法为治疗实体瘤提供了更广泛的可能性。然而,由于鉴定特定抗原肽的复杂过程,其临床应用仍面临重大挑战。因此,我们旨在建立一种新型的“通用”TCR-T“人工抗原表达”技术,该技术涉及使用DSPE-PEG-NY-ESO-1157-165脂质体(NY-ESO-1Lips)将抗原递送至肿瘤细胞,以表达TCR-T细胞特异性识别靶标。体外和体内研究表明,它们可以在肿瘤区域有效积累,并递送靶抗原以激活肿瘤特异性细胞毒性T细胞免疫反应。NY-ESO-1TCR-T疗法,当组合使用时,极大地抑制了肿瘤的进展,延长了小鼠的寿命。此外,PD-1阻断增强了上述疗法的治疗效果。总之,NY-ESO-1嘴唇通过使抗原靶标在其表面表达而“诅咒”肿瘤细胞。这种创新技术为TCR-T在实体瘤治疗中的广泛利用提供了开创性的方法。
    T-cell receptor (TCR) engineered T-cell therapy, unlike chimeric antigen receptor T-cell therapy, relies on the inherent ability of TCRs to detect a wider variety of antigenic epitopes, such as protein fragments found internally or externally on cells. Hence, TCR-T-cell therapy offers broader possibilities for treating solid tumors. However, because of the complicated process of identifying specific antigenic peptides, their clinical application still encounters significant challenges. Thus, we aimed to establish a novel \"universal\" TCR-T \"artificial antigen expression\" technique that involves the delivery of the antigen to tumor cells using DSPE-PEG-NY-ESO-1157-165 liposomes (NY-ESO-1 Lips) to express TCR-T-cell-specific recognition targets. In vitro as well as in vivo studies revealed that they could accumulate efficiently in the tumor area and deliver target antigens to activate the tumor-specific cytotoxic T-cell immune response. NY-ESO-1 TCR-T therapy, when used in combination, dramatically curbed tumor progression and extended the longevity of mice. Additionally, PD-1 blockage enhanced the therapeutic effect of the aforementioned therapy. In conclusion, NY-ESO-1 Lips \"cursed\" tumor cells by enabling antigenic target expression on their surface. This innovative technique presents a groundbreaking approach for the widespread utilization of TCR-T in solid tumor treatment.
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  • 文章类型: Journal Article
    免疫系统在骨折愈合中起着重要作用,通过调节损伤后立即发生的促炎和抗炎反应。这些反应的不平衡会导致不良后果,如骨折不愈合。植入物用于支撑和稳定复杂的骨折。可生物降解的金属植入物提供了避免第二次手术切除植入物的潜力。不像不可降解的植入物。然而,考虑到我们的动态免疫系统,重要的是对生命系统中这些植入物的免疫反应进行深入研究。在这项研究中,我们在带有外固定支架的大鼠股骨骨折模型中研究了体内对Mg和Mg-10Gd的免疫反应。使用脂质体制剂的体内成像用于随时间监测荧光相关的炎症。我们将离体方法与体内研究相结合,以评估和了解植入物对免疫反应的全身和局部影响。随着时间的推移,与SHAM和Mg植入组相比,我们在Mg-10Gd植入组中没有观察到明显的局部或全身效应。我们的研究结果表明,Mg-10Gd是一种比Mg更相容的植入材料,在我们为期4周的研究中,在骨折愈合的早期没有观察到不良反应。重要性声明:在大鼠股骨骨折模型中评估Mg和Mg-10Gd髓内钉形式的可降解金属植入物,与未植入SHAM组一起,特别是在诱导炎症反应的潜力方面。这项临床前研究结合了创新的非侵入性体内成像技术,离体细胞和分子分析。该研究有助于可降解生物金属的开发和评估及其临床应用潜力。研究结果表明,与SHAM和Mg组相比,Mg-10Gd没有表现出任何明显的有害作用。
    The immune system plays an important role in fracture healing, by modulating the pro-inflammatory and anti-inflammatory responses occurring instantly upon injury. An imbalance in these responses can lead to adverse outcomes, such as non-union of fractures. Implants are used to support and stabilize complex fractures. Biodegradable metallic implants offer the potential to avoid a second surgery for implant removal, unlike non-degradable implants. However, considering our dynamic immune system it is important to conduct in-depth studies on the immune response to these implants in living systems. In this study, we investigated the immune response to Mg and Mg-10Gd in vivo in a rat femur fracture model with external fixation. In vivo imaging using liposomal formulations was used to monitor the fluorescence-related inflammation over time. We combine ex vivo methods with our in vivo study to evaluate and understand the systemic and local effects of the implants on the immune response. We observed no significant local or systemic effects in the Mg-10Gd implanted group compared to the SHAM and Mg implanted groups over time. Our findings suggest that Mg-10Gd is a more compatible implant material than Mg, with no adverse effects observed in the early phase of fracture healing during our 4-week study. STATEMENT OF SIGNIFICANCE: Degradable metallic implants in form of Mg and Mg-10Gd intramedullary pins were assessed in a rat femur fracture model, alongside a non-implanted SHAM group with special respect to the potential to induce an inflammatory response. This pre-clinical study combines innovative non-invasive in vivo imaging techniques associated with multimodal, ex vivo cellular and molecular analytics. The study contributes to the development and evaluation of degradable biometals and their clinical application potential. The study results indicate that Mg-10Gd did not exhibit any significant harmful effects compared to the SHAM and Mg groups.
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  • 文章类型: Journal Article
    钴卟啉磷脂通过抗原多组氨酸标签(His标签)在脂质体表面展示重组蛋白抗原,当与单磷酸化脂质A和QS-21组合时,会产生“CPQ”疫苗佐剂系统。在这项原理证明研究中,CPQ用于产生疫苗原型,其引发针对两种不同甲病毒(AV)的抗体。用计算设计的小鼠免疫,他的标签,代表血清型特异性委内瑞拉马脑炎病毒(VEEVcon)的包膜蛋白2(E2)的可变B结构域的物理化学性质共有(PCPCcon)蛋白抗原或称为EVCCon的广谱AV抗原。CPQ佐剂增强了两种蛋白质的抗原性,而不会引发可检测的抗His标签抗体。与替代对照佐剂相比,从用与CPQ混合的抗原免疫的小鼠中引发的抗体显示出数量级较高水平的抗原特异性IgG。ELISA结果与针对VEEV毒株TC83的抗病毒活性相关,而与基孔肯雅病毒118/25的抗病毒活性较弱。因此,在免疫原性脂质体表面上展示大肠杆菌产生的His标记的E2蛋白片段,在接种疫苗的小鼠中引发高水平的抗原特异性和AV中和抗体,同时促进疫苗制备和提供剂量节省的潜力。
    Cobalt-porphyrin phospholipid displays recombinant protein antigens on liposome surfaces via antigen polyhistidine-tag (His-tag), and when combined with monophosphorylated lipid A and QS-21 yields the \"CPQ\" vaccine adjuvant system. In this proof of principle study, CPQ was used to generate vaccine prototypes that elicited antibodies for two different alphaviruses (AV). Mice were immunized with computationally designed, His-tagged, physicochemical property consensus (PCPcon) protein antigens representing the variable B-domain of the envelope protein 2 (E2) from the serotype specific Venezuelan Equine Encephalitis Virus (VEEVcon) or a broad-spectrum AV-antigen termed EVCcon. The CPQ adjuvant enhanced the antigenicity of both proteins without eliciting detectable anti-His-tag antibodies. Antibodies elicited from mice immunized with antigens admixed with CPQ showed orders-of-magnitude higher levels of antigen-specific IgG compared to alternative control adjuvants. The ELISA results correlated with antiviral activity against VEEV strain TC83 and more weakly to Chikungunya virus 118/25. Thus, display of E.coli-produced His-tagged E2 protein segments on the surface of immunogenic liposomes elicits high levels of antigen-specific and AV neutralizing antibodies in mice with vaccination, while facilitating vaccine preparation and providing dose-sparing potential.
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