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基于可生物降解介孔有机硅的纳米稳定剂靶向肥大细胞用于过敏性疾病的长期治疗。

Biodegradable Mesoporous Organosilica-Based Nanostabilizer Targeting Mast Cells for Long-Term Treatment of Allergic Diseases.

机构信息

Key Laboratory of Flexible Electronics (KLOFE), School of Flexible Electronics (Future Technologies) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, China.

Department of Pharmacy, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing 210009, China.

出版信息

ACS Nano. 2024 Jul 2;18(26):16934-16946. doi: 10.1021/acsnano.4c03069. Epub 2024 Jun 22.

DOI:10.1021/acsnano.4c03069
PMID:38907988
Abstract

Allergic diseases are immune system dysfunctions mediated by mast cell (MC) activation stimulated by specific allergens. However, current small molecular MC stabilizers for allergic disease prevention often require multiple doses over a long period of time and are associated with serious side effects. Herein, we develop a diselenide-bridged mesoporous silica nanostabilizer, proving that it could specifically target sensitized MCs via the recognition of IgE aptamer and IgE. Meantime, the IgE aptamer can also mitigate allergic reactions by preventing re-exposure of allergens from the surface of sensitized MCs. Furthermore, the diselenide-bridged scaffold can be reduced by the intracellular excessive ROS, subsequently achieving redox homeostasis via ROS depletion. Finally, the precise release of small molecular MC stabilizers along with the biodegradation of nanocarrier can stabilize the membranes of MCs. assays in passive cutaneous anaphylactic (PCA) and allergic rhinitis (AR) mice indicated that our current strategy further endowed it with a high efficacy, long-term therapeutic time window, as well as negligible inflammatory side effects for allergic diseases, offering a promising therapeutic strategy for the clinical generalization of allergic diseases.

摘要

过敏疾病是由特定过敏原刺激肥大细胞(MC)激活介导的免疫系统功能紊乱。然而,目前用于预防过敏疾病的小分子 MC 稳定剂通常需要长时间多次给药,并且会伴随严重的副作用。在此,我们开发了一种二硒键桥联介孔硅纳米稳定剂,证明它可以通过 IgE 适体和 IgE 的识别特异性靶向致敏的 MC。同时,IgE 适体还可以通过阻止过敏原从致敏 MC 表面重新暴露来减轻过敏反应。此外,二硒键桥联支架可以被细胞内过多的 ROS 还原,从而通过 ROS 耗竭实现氧化还原平衡。最后,小分子 MC 稳定剂的精确释放和纳米载体的生物降解可以稳定 MC 的膜。在被动皮肤过敏(PCA)和过敏性鼻炎(AR)小鼠模型中的实验表明,我们的策略进一步赋予了它高效、长期的治疗时间窗以及对过敏疾病的轻微炎症副作用,为过敏疾病的临床推广提供了一种有前景的治疗策略。

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