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新型载吲哚菁绿光热纳米颗粒靶向 TRPV1 用于卵清蛋白和脂多糖诱导的严重哮喘小鼠的热消融治疗。

Novel indocyanine green-loaded photothermal nanoparticles targeting TRPV1 for thermal ablation treatment of severe murine asthma induced by ovalbumin and lipopolysaccharide.

机构信息

Translational Medicine Research Institute, the First People's Hospital of Foshan, Foshan, 528000, PR China; School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Guangzhou, 510275, PR China.

Pulmonary and Critical Care Medicine, the First People's Hospital of Foshan, Foshan, 528000, PR China.

出版信息

Int J Pharm. 2024 Feb 15;651:123778. doi: 10.1016/j.ijpharm.2024.123778. Epub 2024 Jan 3.

DOI:10.1016/j.ijpharm.2024.123778
PMID:38181990
Abstract

To identify a replacement strategy for bronchial thermoplasty (BT) with non-invasive and free-of-severe side effect is urgently needed in the clinic for severe asthma treatment. In this study, PLGA-PEG@ICG@TRPV1 pAb (PIT) photothermal nanoparticles targeting bronchial TRPV1 were designed for photothermal therapy (PTT) against severe murine asthma induced by ovalbumin and lipopolysaccharide. PIT was formulated with a polyethylene glycol (PEG)-grafted poly (lactic-co-glycolic) acid (PLGA) coating as a skeleton structure to encapsulate indocyanine green (ICG) and was conjugated to the polyclonal antibody against transient receptor potential vanilloid 1 (TRPV1 pAb). The results revealed that PIT held good druggability due to its electronegativity and small diameter. PIT demonstrated great photothermal effects both in vivo and in vitro and exhibited good ability to target TRPV1 in vitro because of its selective cell uptake and specific cell toxicity toward TRPV1-overexpressing cells. The PIT treatment effectively reduced asthma symptoms in mice. This is evident from improvements in expiratory airflow limitation, significant decreases in inflammatory cell infiltration in the airways, and increases in goblet cell and columnar epithelial cell proliferation. In conclusion, PIT alleviates severe murine asthma symptoms through a combination of TRPV1 targeting and photothermal effects.

摘要

为了寻找一种替代支气管热成形术(BT)的策略,临床上迫切需要一种针对严重哮喘治疗的非侵入性且无严重副作用的方法。在这项研究中,设计了针对支气管 TRPV1 的 PLGA-PEG@ICG@TRPV1 pAb(PIT)光热纳米粒子,用于针对卵清蛋白和脂多糖诱导的严重小鼠哮喘的光热治疗(PTT)。PIT 采用聚乙二醇(PEG)接枝聚(乳酸-共-乙醇酸)(PLGA)作为骨架结构包裹吲哚菁绿(ICG),并与针对瞬时受体电位香草素 1(TRPV1 pAb)的多克隆抗体偶联。结果表明,由于其电负性和小直径,PIT 具有良好的成药性。PIT 在体内和体外均表现出良好的光热效应,并表现出良好的靶向 TRPV1 的能力,因为它对 TRPV1 过表达细胞具有选择性细胞摄取和特异性细胞毒性。PIT 治疗有效减轻了小鼠的哮喘症状。这从呼气气流受限的改善、气道炎症细胞浸润的显著减少以及杯状细胞和柱状上皮细胞增殖的增加中可以明显看出。总之,PIT 通过靶向 TRPV1 和光热效应的结合缓解了严重的小鼠哮喘症状。

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引用本文的文献

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