Therapeutic Targeting of Lung Adenocarcinoma with Mannose-Coated Chitosan/Copper Nanocluster–Levocetirizine Nanocomposite

Lung adenocarcinoma is regarded as the most common form of lung cancer, per the latest epidemiological data. The combined efforts from chemotherapy and radiotherapy have done little to increase survival rates. Thus, repurposing licensed drugs has become a feasible approach to filling such gaps. Levocetirizine dihydrochloride, a common antihistamine, has been loaded into copper nanoclusters. The subsequent levocetirizine loaded copper nanoclusters were loaded into mannose functionalized chitosan nanoparticles. This therapeutic module has been established to target lung adenocarcinoma cells in both the monolayer and tumor spheroids. The nanocomposite was found to be inherently fluorescent, biocompatible, and water-soluble. The drug release profile was found to be pH-dependent, with maximum release in the acidic medium. Experimental results concluded efficient cellular localization followed by significant antiproliferative activity. Subsequent functional assays revealed suggestive reactive oxygen species generation, membrane potential depolarization, and reduced lipid droplets leading up to apoptosis. A remarkable reduction in colony formation and migration capacity was also observed. They also inhibited the spheroids of both A549 and HeLa cells. Briefly, the as-synthesized nanocomposites showed a promising scope as an anticancer treatment approach.