Hamrick Samantha K, Thompson Michael A, Rotello Vincent M, Prakash Y S, Pabelick Christina M
Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States.
Department of Chemistry, University of Massachusetts, Amherst, Massachusetts, United States.
Am J Physiol Lung Cell Mol Physiol. 2024 Dec 1;327(6):L964-L971. doi: 10.1152/ajplung.00248.2024. Epub 2024 Oct 29.
Asthma is a heterogeneous chronic lung disease that affects nearly 340 million people globally. Airway hyperresponsiveness, remodeling (thickening and fibrosis), and mucus hypersecretion are some hallmarks of asthma. With several current treatments having serious side effects from long-term use and a proportion of patients with uncontrolled asthma, there is an urgent need for new therapies. With an increasing understanding of asthma pathophysiology, there is a recognized need to target therapies to specific cell types of the airway, which necessitates the identification of delivery systems that can overcome increased mucus and thickened airways. Nanoparticles (NPs) that are highly customizable (material, size, charge, and surface modification) are a potential solution for delivery systems of a wide variety of cargoes (nucleic acids, proteins, and/or small molecules), as well as sole therapeutics for asthma. However, there is a need to consider the safety of the NPs in terms of potential for inflammation, toxicity, nonspecific targets, and accumulation in organs. Ongoing clinical trials using NPs, some FDA-approved for therapeutics in other diseases, provide confidence regarding the potential safety and efficacy of NPs in asthma treatment. This review highlights the current state of the use of NPs in asthma, identifying opportunities for further improvements in NP design and utilization for targeting this chronic lung disease.
哮喘是一种异质性慢性肺部疾病,全球有近3.4亿人受其影响。气道高反应性、重塑(增厚和纤维化)以及黏液高分泌是哮喘的一些特征。由于目前的几种治疗方法长期使用会产生严重副作用,且有一部分哮喘患者病情控制不佳,因此迫切需要新的治疗方法。随着对哮喘病理生理学的认识不断加深,人们认识到需要针对气道的特定细胞类型进行靶向治疗,这就需要确定能够克服黏液增多和气道增厚的给药系统。纳米颗粒(NPs)具有高度可定制性(材料、尺寸、电荷和表面修饰),是多种货物(核酸、蛋白质和/或小分子)给药系统的潜在解决方案,也是哮喘的单一治疗药物。然而,需要从炎症、毒性、非特异性靶点以及在器官中的积累等方面考虑纳米颗粒的安全性。正在进行的使用纳米颗粒的临床试验,其中一些已获美国食品药品监督管理局批准用于其他疾病的治疗,这为纳米颗粒在哮喘治疗中的潜在安全性和有效性提供了信心。本综述重点介绍了纳米颗粒在哮喘治疗中的应用现状,确定了在纳米颗粒设计和用于治疗这种慢性肺部疾病方面进一步改进的机会。