Stimuli-responsive nanoparticles for lung disorder treatment: From serendipity to precision phosphorylation modulation and drug repurposing

From the serendipitous discovery of penicillin, X-rays, and streptomycin to transformative innovations that target disease signaling pathways, all these findings have played a pivotal role in shaping pulmonary medicine. This study outlines the different categories of stimuli-responsive nanoparticles (NPs) that can encapsulate different medications. Stimuli-responsive NPs are designed to react to external triggers (e.g., light, magnetic fields) or internal triggers (e.g., pH, enzymes, temperature), enabling site-specific delivery of therapeutic agents, and offering innovative solutions for treating lung disorders. The review also emphasizes three principal phosphorylation pathways: the inflammatory NF-κB pathway, the fibrotic TGF-β pathway, and the carcinogenic IGF-1 pathway. Since NF-ӄB, TGF-β, and IGF-1 are the main signaling pathways included in many diseases in the human body, targeting these signaling pathways would treat not only lung diseases but also other diseases caused by the dysregulation of these signals. Unlike conventional therapies that use free drugs for pulmonary illnesses, the application of stimuli-responsive NPs to encapsulate serendipitous drugs and drugs aimed at phosphorylation signaling pathways exhibits improved therapeutic effectiveness and reduced toxicity. Notably, encapsulating serendipitously discovered drugs, such as statins and quinine, alongside phosphorylation-targeting agents like resveratrol and curcumin in stimuli-responsive NPs underscores the potential of drug repurposing to enhance lung disorder treatments. • Serendipitous discoveries have revolutionized therapies for lung diseases. • Targeting NF-κB, TGF-β, and IGF-1 phosphorylation shows promise for lung therapy. • The interplay of NF-κB, TGF-β, and IGF-1 pathways drives lung disease progression. • Stimuli-responsive nanoparticles (NPs) enhance drug efficacy and reduce side effects. • Repurposing serendipitous, multi-pathway-targeted drugs in NPs expands lung therapies.