Selective imaging, gene, and therapeutic delivery using PEGylated and pH-Sensitive nanoparticles for enhanced lung disorder treatment

Lung inflammation involves the activation of immune cells and inflammatory mediators in response to injury and infection. When inflammation persists, fibroblasts, which are resident lung cells, become activated, leading to pulmonary fibrosis (PF), abnormal wound healing, and long-term damage to the alveolar epithelium. This persistent inflammation and fibrosis can also elevate the risk of lung cancer, emphasizing the need for innovative treatments. Current therapies, such as inhaled corticosteroids (ICS) and chemotherapy, have significant limitations. Although conventional nanoparticles (NPs) provide a promising avenue for treating lung disorders, they have limited selectivity and stability. Polyethylene glycol (PEG) grafting can prevent NP aggregation and phagocytosis, thus prolonging their circulation time. When combined with targeting ligands, PEGylated NPs can deliver drugs precisely to specific cells or tissues. Moreover, pH-sensitive NPs offer the advantage of selective drug delivery to inflammatory or tumor-acidic environments, reducing side effects. These NPs can change their size, shape, or surface charge in response to pH variations, improving drug delivery efficiency. This review examines the techniques of PEGylation, the polymers used in pH-sensitive NPs, and their therapeutic applications for lung inflammation, fibrosis, and cancer. By harnessing innovative NP technologies, researchers can develop effective therapies for respiratory conditions, addressing unmet medical needs and enhancing patient outcomes.