Hierarchical pulmonary target nanoparticles via inhaled administration for anticancer drug delivery.
Hierarchical pulmonary target nanoparticles via inhaled administration for anticancer drug delivery.
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通过吸入给药的分级肺部靶纳米粒子用于抗癌药物输送
DOI：
10.1080/10717544.2017.1365395
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发表时间：
2017-11
期刊：
影响因子：
6
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Chen R;Xu L;Fan Q;Li M;Wang J;Wu L;Li W;Duan J;Chen Z
与静脉给药相比，吸入给药可显著增加化疗药物在肺组织中的暴露，从而提高肺肿瘤的治疗效果。然而，吸入药物肺沉积后进一步识别癌细胞是必要的，以避免对正常肺组织的副作用，并最大限度地提高药物疗效。此外，由于药物的主要作用部位是细胞内的细胞器，因此药物靶向细胞器是药物准确释放的最终关键。本文设计了一种新型的多功能肺抗肿瘤纳米颗粒（MNP），该材料具有肺组织靶向、癌细胞靶向和线粒体靶向等多层次靶点。采用超高效液相色谱-串联质谱法测定体内生物分布，以验证吸入给药与静脉给药相比，药物在肺组织中的浓度显著增加。利用A549细胞进行的细胞摄取试验证明了有效的受体介导的细胞内吞作用。激光共聚焦扫描显微镜观察显示，MNP在细胞内定位于线粒体。所有结果证实了智能材料可以逐步发挥分级靶向功能，从而诱导更多与线粒体损伤相关的细胞凋亡。它为肺部抗癌药物的分级靶向提供了一个智能、高效的纳米载体平台。这种材料作为肺靶向材料，目前尚未见报道。
Abstract Inhalation administration, compared with intravenous administration, significantly enhances chemotherapeutic drug exposure to the lung tissue and may increase the therapeutic effect for pulmonary anticancer. However, further identification of cancer cells after lung deposition of inhaled drugs is necessary to avoid side effects on normal lung tissue and to maximize drug efficacy. Moreover, as the action site of the major drug was intracellular organelles, drug target to the specific organelle is the final key for accurate drug delivery. Here, we designed a novel multifunctional nanoparticles (MNPs) for pulmonary antitumor and the material was well-designed for hierarchical target involved lung tissue target, cancer cell target, and mitochondrial target. The biodistribution in vivo determined by UHPLC–MS/MS method was employed to verify the drug concentration overwhelmingly increasing in lung tissue through inhaled administration compared with intravenous administration. Cellular uptake assay using A549 cells proved the efficient receptor-mediated cell endocytosis. Confocal laser scanning microscopy observation showed the location of MNPs in cells was mitochondria. All results confirmed the intelligent material can progressively play hierarchical target functions, which could induce more cell apoptosis related to mitochondrial damage. It provides a smart and efficient nanocarrier platform for hierarchical targeting of pulmonary anticancer drug. So far, this kind of material for pulmonary mitochondrial-target has not been seen in other reports.
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影响因子：
4.9
作者：
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DOI：
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