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首页> 美国卫生研究院文献>International Journal of Nanomedicine >Defect density in multiwalled carbon nanotubes influences ovalbumin adsorption and promotes macrophage activation and CD4+ T-cell proliferation
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Defect density in multiwalled carbon nanotubes influences ovalbumin adsorption and promotes macrophage activation and CD4+ T-cell proliferation

机译：多壁碳纳米管中的缺陷密度影响卵白蛋白的吸附并促进巨噬细胞活化和CD4 + T细胞增殖

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Carbon nanotubes (CNTs) are of great interest for the development of drugs and vaccines due to their unique physicochemical properties. The high surface area to volume ratio and delocalized pi-electron cloud of CNTs promote binding of proteins to the surface forming a protein corona. This unique feature of CNTs has been recognized for potential delivery of antigens for strong and long-lasting antigen-specific immune responses. Based on an earlier study that demonstrated increased protein binding, we propose that carboxylated multiwalled CNTs (MWCNTs) can function as an improved carrier to deliver antigens such as ovalbumin (OVA). To test this hypothesis, we coated carboxylated MWCNTs with OVA and measured uptake and activation of antigen-presenting cells (macrophages) and their ability to stimulate CD4+ T-cell proliferation. We employed two types of carboxylated MWCNTs with different surface areas and defects (MWCNT-2 and MWCNT-30). MWCNT-2 and MWCNT-30 have surface areas of ~215 m2/g and 94 m2/g, respectively. The ratios of D- to G-band areas (ID/IG) were 0.97 and 1.37 for MWCNT-2 and MWCNT-30, respectively, samples showing that MWCNT-30 contained more defects. The increase in defects in MWCNT-30 led to increased binding of OVA as compared to MWCNT-2 (1,066±182 μg/mL vs 582±41 μg/mL, respectively). Both types of MWCNTs, along with MWCNT–OVA complexes, showed no observable toxicity to bone-marrow-derived macrophages up to 5 days. Surprisingly, we found that MWCNT–OVA complex significantly increased the expression of major histocompatibility complex class II on macrophages and production of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin 6), while MWCNTs without OVA protein corona did not. The coculture of MWCNT–OVA-complex-treated macrophages and OVA-specific CD4+ T-cells isolated from OT-II mice demonstrated robust proliferation of CD4+ T-cells. This study provides strong evidence for a role for defects in carboxylated MWCNTs and their use in the efficient delivery of antigens for the development of next-generation vaccines.
机译：碳纳米管（CNTs）由于其独特的物理化学特性，对药物和疫苗的开发非常感兴趣。碳纳米管的高表面积体积比和离域π电子云促进了蛋白质与表面的结合，从而形成了蛋白质电晕。 CNT的这一独特功能已被公认可以潜在地传递抗原，从而产生强而持久的抗原特异性免疫反应。基于较早的研究表明蛋白质结合增加，我们建议羧基化的多壁碳纳米管（MWCNT）可以作为改进的载体来传递抗原，例如卵清蛋白（OVA）。为了验证这一假设，我们用OVA包被了羧化的MWCNTs，并测量了抗原呈递细胞（巨噬细胞）的摄取和激活以及它们刺激CD4 + T细胞增殖的能力。我们采用了两种具有不同表面积和缺陷的羧化MWCNT（MWCNT-2和MWCNT-30）。 MWCNT-2和MWCNT-30的表面积分别为〜215 m 2 / g和94 m 2 / g。对于MWCNT-2和MWCNT-30，D带与G带的面积比（ID / IG）分别为0.97和1.37，样品表明MWCNT-30包含更多的缺陷。与MWCNT-2相比，MWCNT-30中缺陷的增加导致OVA结合增加（分别为1,066±182μg/ mL和582±41μg/ mL）。两种类型的MWCNT，以及MWCNT-OVA复合物，在长达5天的时间里都没有观察到对源自骨髓的巨噬细胞的毒性。令人惊讶的是，我们发现MWCNT-OVA复合物显着增加了主要组织相容性复合物II类在巨噬细胞上的表达和促炎细胞因子（肿瘤坏死因子-α和白介素6）的产生，而没有OVA蛋白电晕的MWCNT没有。从OT-II小鼠分离得到的MWCNT–OVA复合物处理的巨噬细胞和OVA特异性CD4 + T细胞的共培养表明CD4 + T细胞具有较强的增殖能力。这项研究为羧化碳纳米管中的缺陷及其在有效递送抗原以开发下一代疫苗中的作用提供了强有力的证据。

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