Borkar, Niyati

siRNA delivery to target cellular processes is an appealing area in lung diseases such as asthma. To realize this potential requires efficient, targeted cytosolic delivery without cellular toxicity or siRNA degradation. We demonstrate the efficacy of PONI-Guan nanoparticles in accessing airway epithelial and smooth muscle cells with specific siRNA targeting of mRNAs of interest while maintaining barrier integrity and avoiding cellular toxicity.

Iron is an important metal element regulating biological processes such as gene expression, electron transport, cell proliferation, differentiation and division, and cellular respiration. Regulation of iron levels is therefore critical, with excess iron accumulation leading to iron-dependent lipid peroxidation and cell death (ferroptosis). Factors such as aging and environmental exposures (e.g., high/low oxygen, particulate iron) can disrupt iron homeostasis. Iron-dependent processes influence downstream pathways such as inflammation, mitochondrial energetics, and remodeling (proliferation, fibrosis), pathways involved in lung diseases particularly at the extremes of age, from hyperoxic lung injury in neonates to chronic diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF) that increase with age. Although these diseases involve structural and functional changes in bronchial versus alveolar compartments, including airway hyperreactivity, altered mucus production, cell proliferation and migration, increased extracellular matrix (ECM) remodeling, senescence, and metabolic dysregulation, the casual or consequential links between iron dysregulation and disease pathology, particularly with aging, are still being investigated. The aim of this topical review is to 1) highlight current knowledge regarding iron regulation in normal lung versus lung diseases, 2) identify known roles of iron in lung homeostasis and the contribution of iron dysregulation in lung diseases with aging, and 3) explore the potential benefit of targeting iron regulation and/or ferroptosis in lung diseases.