Targeted delivery of pentagalloyl glucose inhibits matrix metalloproteinase activity and preserves elastin in emphysematous lungs.
Targeted delivery of pentagalloyl glucose inhibits matrix metalloproteinase activity and preserves elastin in emphysematous lungs.
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DOI：
10.1186/s12931-021-01838-1
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发表时间：
2021-09-18
影响因子：
5.8
通讯作者：
Vyavahare N
中科院分区：
文献类型：
--
作者：
Parasaram V;Wang X;Krisanarungson P;Vyavahare N
弹性蛋白降解已被确定为肺气肿的驱动因素之一。弹性蛋白衍生的多肽(EDPs)被证明是单核细胞的趋化物质。有效地保护弹性蛋白免受弹性损伤和再生丢失的弹性蛋白是改善受损肺机械功能的两个重要步骤。在体内，五甲基葡萄糖(PGG)被证明可以保护血管组织中的弹性蛋白免受弹性蛋白的损伤，并在体外有助于弹性蛋白的沉积。我们通过吸入弹性酶激发小鼠造成肺气肿。负载PGG的白蛋白纳米粒与弹性蛋白抗体偶联，靶向肺内降解的弹性蛋白。我们通过测量动态顺应性和潮气量变化来研究基质金属蛋白酶-12的活性和肺损伤。体外实验表明，与对照组相比，经PGG处理的样品中弹性蛋白得以保存。吸入的纳米颗粒与弹性蛋白抗体结合，可在肺部保留较长时间。此外，用PGG纳米颗粒治疗的小鼠表现出对肺部测量的基质金属蛋白酶-12活性的显著抑制。与对照组相比，我们在动态肺顺应性和潮气量变化方面观察了肺气肿的抑制。组织学检查进一步证实肺内有弹性蛋白保留。这些结果表明，成功地靶向输送了负载PGG的纳米颗粒来抑制基质金属蛋白酶-12的活性，并保留了肺中的弹性蛋白。这种靶向PGG疗法在肺气肿的治疗中具有潜在的治疗用途。网上版载有补充材料，可在10.1186/s12931-021-01838-1查阅。
Elastin degradation has been established as one of the driving factors of emphysema. Elastin-derived peptides (EDPs) are shown to act as a chemoattractant for monocytes. Effectively shielding elastin from elastolytic damage and regenerating lost elastin are two important steps in improving the mechanical function of damaged lungs. Pentagalloyl glucose (PGG) has been shown to preserve elastin in vascular tissues from elastolytic damage in vivo and aid in elastin deposition in vitro. We created emphysema by elastase inhalation challenge in mice. Albumin nanoparticles loaded with PGG, conjugated with elastin antibody, were delivered to target degraded elastin in lungs. We investigated matrix metalloproteinase-12 activity and lung damage by measuring dynamic compliance and tidal volume changes. Ex-vivo experiments demonstrated elastin preservation in PGG treated samples compared to controls. Inhaled nanoparticles conjugated with elastin antibody retained for extended periods in lungs. Further, mice treated with PGG nanoparticles showed a significant suppression of MMP-12 activity measured in the lungs. We observed suppression of emphysema in terms of dynamic lung compliance and tidal volume change compared to the control group. The histological examination further confirmed elastin preservation in the lungs. These results demonstrate successful targeted delivery of nanoparticles loaded with PGG to inhibit MMP-12 activity and preserve elastin in the lungs. Such targeted PGG therapy has potential therapeutic use in the management of emphysema. The online version contains supplementary material available at 10.1186/s12931-021-01838-1.
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DOI：
10.1016/j.jconrel.2014.09.029
发表时间：
2014-12-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Lei Y;Nosoudi N;Vyavahare N
通讯作者：
Vyavahare N
在小鼠模型中锻炼肺肺气肿的耐受性和全身表现。
影响因子：
5.8
作者：
Lüthje L;Raupach T;Michels H;Unsöld B;Hasenfuss G;Kögler H;Andreas S
通讯作者：
Andreas S
影响因子：
3.3
作者：
Ito, S;Ingenito, EP;Suki, B
通讯作者：
Suki, B
影响因子：
37.8
作者：
Isenburg, Jason C.;Simionescu, Dan T.;Vyavahare, Narendra R.
通讯作者：
Vyavahare, Narendra R.
影响因子：
10
作者：
Churg, Andrew;Wang, Rona;Wright, Joanne L.
通讯作者：
Wright, Joanne L.