Rational design of oral drugs targeting mucosa delivery with gut organoid platforms.
Rational design of oral drugs targeting mucosa delivery with gut organoid platforms.
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DOI：
10.1016/j.bioactmat.2023.07.014
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发表时间：
2023-12
影响因子：
18.9
通讯作者：
中科院分区：
文献类型：
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作者：
有效的口服药物和疫苗需要穿过胃肠上皮的高递送效率和保护医学有效的有效载荷（即，免疫原）对抗胃损伤。本研究探索了具有聚赖氨酸（PLL）涂层和哺乳动物正呼肠孤病毒细胞粘附蛋白σ1（NC-PLL-σ1）功能化的中空纳米载体（NC：二氧化硅纳米球和金纳米笼）作为功能性口服药物递送载体（ODDVs）。微折叠细胞（M细胞）介导的跨胃肠道上皮的转胞吞作用（通过σ1-α2-3-连接的唾液酸粘附）可促进这些ODDV转运至粘膜淋巴组织。PLL涂层提供了保护和缓释罗丹明6 G（R6 G），一个模型的有效载荷。这些ODDV的运输效力在体外肠类器官单层上进行了测试。当与其他实验组相比时，完全功能化的ODDV系统（具有PLL-σ1）表现出两个显著的优点：显著更高的转运效率（在48 h时超过空白对照的198%）;以及有效载荷的保护，这导致更好的转运效率和有效载荷的延长释放（在48 h时超过未涂覆的载体的61%）。此外，显示肠类器官单层中的M细胞存在（通过Rank L刺激调节）是ODDV的转运效率的决定因素：类器官单层中更多的M细胞（通过更高的Rank L诱导）导致ODDV递送的模型有效载荷（R6 G）的更高的转运效率。完全功能化的ODDVs作为药物和疫苗的有效口服载体显示出巨大的潜力。我们合理设计了人工病毒纳米粒作为口服给药载体。在肠道类器官粘膜模型上测试ODDV的递送有效性。ODDV（具有PLL-σ1）显著提高了输送效率。我们强调M细胞是ODDV效率的重要因素。
Effective oral drugs and vaccines require high delivery efficiency across the gastrointestinal epithelia and protection of medically effective payloads (i.e., immunogens) against gastric damage. In this study, hollowed nanocarriers (NCs: silica nanospheres and gold nanocages) with poly-l-lysine (PLL) coating and mammalian orthoreovirus cell attachment protein σ1 functionalization (NC-PLL-σ1) were explored as functional oral drug delivery vehicles (ODDVs). The transport of these ODDVs to mucosal lymphoid tissues could be facilitated by microfold cells (M-cells) mediated transcytosis (via σ1-α2–3-linked sialic acids adherence) across gastrointestinal epithelia. PLL coating provided protection and slow-release of rhodamine 6 G (R6G), a model payload. The transport effectiveness of these ODDVs was tested on intestinal organoid monolayers in vitro. When compared with other experimental groups, the fully functionalized ODDV system (with PLL-σ1) demonstrated two significant advantages: a significantly higher transport efficiency (198% over blank control at 48 h); and protection of payloads which led to both better transport efficiency and extended-release of payloads (61% over uncoated carriers at 48 h). In addition, it was shown that the M cell presence in intestinal organoid monolayers (modulated by Rank L stimulation) was a determining factor on the transport efficiency of the ODDVs: more M-cells (induced by higher Rank L) in the organoid monolayers led to higher transport efficiency for ODDV-delivered model payload (R6G). The fully functionalized ODDVs showed great potential as effective oral delivery vehicles for drugs and vaccines. We rational designed artificial virus nanoparticles as oral drug delivery vehicles (ODDVs). The delivery effectiveness of ODDVs was tested on gut organoid mucosal models. The ODDVs (with PLL-σ1) significantly improved delivery efficiency. We highlighted that the M cell was a vital factor in the efficiency of the ODDVs.
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影响因子：
3.1
作者：
Mendez, II;Hermann, LL;Coombs, KM
通讯作者：
Coombs, KM
影响因子：
2.9
作者：
Pokharkar, Varsha;Bhumkar, Devika;Jadhav, S. S.
通讯作者：
Jadhav, S. S.
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3.7
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Cai T;Qi Y;Jergens A;Wannemuehler M;Barrett TA;Wang Q
通讯作者：
Wang Q
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4.6
作者：
Altay, Gizem;Larranaga, Enara;Martinez, Elena
通讯作者：
Martinez, Elena
影响因子：
3.9
作者：
Bartczak, Dorota;Kanaras, Antonios G.
通讯作者：
Kanaras, Antonios G.