Seydoux Emilie, Fytianos Kleanthis, Garnier Christophe von, Rothen-Rutishauser Barbara, Blank Fabian
Department of Biomedical Research, University of Bern, Bern, Switzerland.
J Aerosol Med Pulm Drug Deliv. 2024 Dec;37(6):328-337. doi: 10.1089/jamp.2024.63954.es.
The respiratory tract with its vast surface area and very thin air-blood tissue barrier presents an extremely large interface for potential interaction with xenobiotics such as inhaled pathogens or medicaments. To protect its large and vulnerable surface, the lung is populated with several different types of immune cells. Pulmonary epithelial cells, macrophages and dendritic cells are key players in shaping the innate and adaptive immune response. Due to their localization, they represent a frontline of cell populations that are among the first to come in contact with inhaled xenobiotics. Furthermore, depending on the lung compartment they populate, these cells show a large variety in morphology, phenotype, and function. These unique characteristics make those cell populations ideal targets for specific immunomodulators that are designed for inhalation. Depending on cell population or lung compartment targeting, a specific immune response may be triggered or modulated. The purpose of a potent carrier for pulmonary immunomodulation is, first, to efficiently target a specific immunocompetent cell and, second, to affect its role in generating an immune response. Immunomodulation may occur at different levels of immune cell-antigen interaction, i.e. antigen uptake, trafficking, processing and presentation. Inhalation of nanosized carriers for drugs or vaccines shows great potential for both prophylactic and therapeutic approaches in order to modulate immune responses locally or systemically, due to the specific deposition and targeting properties of nanoparticles. Immune responses triggered by nanosized particles may be either immunostimulatory or immunosuppressive and depending on the specific purpose, stimulation or suppression may either be desired or unwanted. Meticulous analysis of immunomodulatory potential, pharmacologic and toxicologic testing of inhalable nanocarriers is required in order to find novel and optimal approaches for prophylaxis and therapy of pulmonary diseases. The design and characterization of such nanoparticles requires well-coordinated interdisciplinary research among engineers, biologists and clinicians.
呼吸道具有巨大的表面积和极薄的气血组织屏障，为与诸如吸入病原体或药物等外源性物质进行潜在相互作用提供了极大的界面。为保护其大面积且脆弱的表面，肺中分布着几种不同类型的免疫细胞。肺上皮细胞、巨噬细胞和树突状细胞是塑造先天性和适应性免疫反应的关键参与者。由于它们的定位，它们代表了最先接触吸入外源性物质的细胞群体的前沿。此外，根据它们所占据的肺腔室不同，这些细胞在形态、表型和功能上表现出很大的差异。这些独特的特征使这些细胞群体成为设计用于吸入的特定免疫调节剂的理想靶点。根据靶向的细胞群体或肺腔室不同，可能会触发或调节特定的免疫反应。一种有效的肺部免疫调节载体的目的，首先是有效地靶向特定的免疫活性细胞，其次是影响其在产生免疫反应中的作用。免疫调节可能发生在免疫细胞 - 抗原相互作用的不同水平，即抗原摄取、运输、加工和呈递。由于纳米颗粒的特定沉积和靶向特性，吸入用于药物或疫苗的纳米级载体在局部或全身调节免疫反应的预防和治疗方法中都显示出巨大潜力。纳米颗粒引发的免疫反应可能是免疫刺激的或免疫抑制的，并且根据具体目的，刺激或抑制可能是期望的或不期望的。为了找到预防和治疗肺部疾病的新颖且最佳方法，需要对可吸入纳米载体的免疫调节潜力进行细致分析以及进行药理和毒理学测试。此类纳米颗粒的设计和表征需要工程师、生物学家和临床医生之间进行良好协调的跨学科研究。
