Nanotechnology-driven delivery of Cordycepin derived from Cordyceps species: Mainly focusing on application of inflammatory pulmonary disease and lung cancer

Inflammatory pulmonary diseases, including acute lung injury, asthma, chronic obstructive pulmonary disease, pulmonary arterial hypertension, and viral respiratory infections, pose a major global health burden and remain challenging to manage with current therapies. Cordycepin (3′-deoxyadenosine), a principal bioactive nucleoside derived from Cordyceps species, has a long history of traditional use for improving lung health and has gained considerable scientific attention for its broad therapeutic potential. This review synthesizes extensive preclinical evidence demonstrating that Cordycepin exerts potent anti-inflammatory, antioxidant, immunomodulatory, and antiviral effects in pulmonary disease models. These actions are mediated through the modulation of key molecular pathways, as well as through the regulation of macrophage polarization and oxidative stress responses. Despite its strong pharmacological activity, the clinical advancement of Cordycepin is limited by rapid metabolic degradation by adenosine deaminase and poor bioavailability. This review highlights these pharmacokinetic challenges and emphasizes the emerging role of nanotechnology-based delivery systems such as liposomes and polymeric nanoparticles in enhancing Cordycepin stability, protecting it from enzymatic deamination, prolonging its circulation, and improving targeted delivery to inflamed lung tissues. By integrating traditional medicinal insights with modern nanotechnology, Cordycepin represents a promising candidate for future therapeutic development in inflammatory pulmonary diseases and lung cancer.