The Materials Science and Engineering Program, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, Ohio; and.
Center for Lung Regenerative Medicine.
Am J Respir Cell Mol Biol. 2021 Mar;64(3):292-307. doi: 10.1165/rcmb.2020-0306TR.
Respiratory disorders are among the most important medical problems threatening human life. The conventional therapeutics for respiratory disorders are hindered by insufficient drug concentrations at pathological lesions, lack of cell-specific targeting, and various biobarriers in the conducting airways and alveoli. To address these critical issues, various nanoparticle delivery systems have been developed to serve as carriers of specific drugs, DNA expression vectors, and RNAs. The unique properties of nanoparticles, including controlled size and distribution, surface functional groups, high payload capacity, and drug release triggering capabilities, are tailored to specific requirements in drug/gene delivery to overcome major delivery barriers in pulmonary diseases. To avoid off-target effects and improve therapeutic efficacy, nanoparticles with high cell-targeting specificity are essential for successful nanoparticle therapies. Furthermore, low toxicity and high degradability of the nanoparticles are among the most important requirements in the nanoparticle designs. In this review, we provide the most up-to-date research and clinical outcomes in nanoparticle therapies for pulmonary diseases. We also address the current critical issues in key areas of pulmonary cell targeting, biosafety and compatibility, and molecular mechanisms for selective cellular uptake.
呼吸系统疾病是威胁人类生命的最重要的医学问题之一。传统的呼吸系统疾病治疗方法受到以下因素的限制:在病变部位药物浓度不足、缺乏细胞特异性靶向性、以及在气道和肺泡中存在各种生物屏障。为了解决这些关键问题,已经开发了各种纳米颗粒给药系统,用作特定药物、DNA 表达载体和 RNA 的载体。纳米颗粒的独特性质,包括可控的大小和分布、表面官能团、高载药能力和药物释放触发能力,根据药物/基因传递的特定要求进行定制,以克服肺部疾病中的主要传递障碍。为了避免脱靶效应并提高治疗效果,具有高细胞靶向特异性的纳米颗粒对于成功的纳米颗粒治疗至关重要。此外,纳米颗粒的低毒性和高可降解性是纳米颗粒设计中最重要的要求之一。在这篇综述中,我们提供了关于用于肺部疾病的纳米颗粒治疗的最新研究和临床结果。我们还讨论了肺部细胞靶向、生物安全性和相容性以及选择性细胞摄取的分子机制等关键领域的当前关键问题。