Effect of MWCNT size, carboxylation, and purification on in vitro and in vivo toxicity, inflammation and lung pathology.
Effect of MWCNT size, carboxylation, and purification on in vitro and in vivo toxicity, inflammation and lung pathology.
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DOI：
10.1186/1743-8977-10-57
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发表时间：
2013-11-13
影响因子：
10
通讯作者：
Holian A
中科院分区：
文献类型：
--
作者：
Hamilton RF Jr;Wu Z;Mitra S;Shaw PK;Holian A
多壁碳纳米管（MWCNT）的几种性质有可能影响其生物活性。本研究检查了多壁碳纳米管的直径、长度、纯化和羧化（仅体外测试）的影响的体外和体内结果。三个原始的“收到的”MWCNT，不同的大小（直径和长度）进行纯化和功能化的羧化。使用来自C57 BL/6小鼠的THP-1细胞和原代肺泡巨噬细胞对所得MWCNT进行表征并检查其体外细胞毒性和炎性小体活化。口咽抽吸给药用于递送原始MWCNT，并在第1天和第7天检查体内生物活性和肺滞留。用THP-1巨噬细胞的研究表明，增加的长度或直径对应于增加的生物活性，如通过炎性小体活化测量的。纯化对原始MWCNT的影响很小，功能化完全消除了生物活性。使用从C57 BL/6小鼠分离的肺泡巨噬细胞获得了类似的结果。体内研究表明，所有三种原始MWCNT在一天内引起相似的中性粒细胞内流，但长度或直径的增加导致灌洗细胞在体外释放更多的炎性细胞因子（IL-6、TNF-α和IL-1β）。7天的组织学显示，与体外结果一致，MWCNT的宽度或长度增加引起更严重的病理，最长的MWCNT引起最严重的炎症。此外，相同的两个较大的MWCNT在第7天更多地保留在肺中。总之，结果表明多壁碳纳米管的体外和体内生物活性随着直径和长度的增加而增加。纯化对原始MWCNT没有显著的改性作用。通过羧化的功能化完全消除了MWCNT的生物活性潜力，而不管其在体外测试中的大小。
Several properties of multi-walled carbon nanotubes (MWCNT) have the potential to affect their bioactivity. This study examined the in vitro and in vivo outcomes of the influence of diameter, length, purification and carboxylation (in vitro testing only) of MWCNT. Three original ‘as received’ MWCNT that varied in size (diameter and length) were purified and functionalized by carboxylation. The resulting MWCNT were characterized and examined for cytotoxicity and inflammasome activation in vitro using THP-1 cells and primary alveolar macrophages from C57BL/6 mice. Oropharyngeal aspiration administration was used to deliver original MWCNT and in vivo bioactivity and lung retention was examined at 1 and 7 days. Studies with THP-1 macrophages demonstrated that increased length or diameter corresponded with increased bioactivity as measured by inflammasome activation. Purification had little effect on the original MWCNT, and functionalization completely eliminated bioactivity. Similar results were obtained using alveolar macrophages isolated from C57BL/6 mice. The in vivo studies demonstrated that all three original MWCNT caused similar neutrophil influx at one day, but increasing length or diameter resulted in the lavaged cells to release more inflammatory cytokines (IL-6, TNF-α, and IL-1β) ex vivo. Seven-day histology revealed that, consistent with the in vitro results, increasing width or length of MWCNT caused more severe pathology with the longest MWCNT causing the most severe inflammation. In addition, the same two larger MWCNT were retained more in the lung at 7 days. Taken together, the results indicated that in vitro and in vivo bioactivity of MWCNT increased with diameter and length. Purification had no significant modifying effect from the original MWCNT. Functionalization by carboxylation completely eliminated the bioactive potential of the MWCNT regardless of size in in vitro testing.
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影响因子：
5
作者：
Girtsman TA;Beamer CA;Wu N;Buford M;Holian A
通讯作者：
Holian A
影响因子：
10.4
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影响因子：
10
作者：
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通讯作者：
Holian A
影响因子：
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作者：
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通讯作者：
Mitra, Somenath
影响因子：
5
作者：
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通讯作者：
Castranova, Vincent