Chia Meets Chitosan: Nanomedicine for Lung Cancer

Delivering anticancer agents directly to the lung offers an attractive opportunity to increase local drug exposure while reducing the limitations associated with systemic administration. Yet many promising bioactive compounds, including quercetin, remain difficult to translate because of poor aqueous solubility and limited bioavailability. Here, we developed an inhalable natural-polymer nanocarrier combining chitosan and Salvia hispanica (chia seed) polysaccharide to enhance quercetin delivery to lung cancer cells. Quercetin-loaded chitosan–chia polysaccharide nanoparticles were prepared as a natural polyelectrolyte complex and evaluated for physicochemical properties, drug incorporation, release, aerosol performance and anticancer activity. The optimized formulation contained quercetin at 0.01% w/v, chitosan at 0.04% w/v, and chia seed polysaccharide at 0.03% w/v. The resulting nanoparticles were quasi-spherical, with a mean hydrodynamic diameter of 331 ± 14.34 nm, low polydispersity (0.15) and a positive ζ-potential of +36.3 ± 2.56 mV. They achieved 73.8 ± 0.73% encapsulation efficiency and 14.20 ± 0.22% drug loading, while providing sustained biphasic quercetin release over 48 h. Importantly, aerosol testing produced a fine particle dose of 417.7 µg, supporting the pulmonary delivery potential of the formulation. Nanoencapsulation translated into enhanced biological activity. After 48 h, the IC₅₀ of quercetin decreased from 197.4 to 78.8 µg/mL in A549 cells and from 69.7 to 56.5 µg/mL in H460 cells. Nanoparticle treatment also enhanced intracellular uptake and ROS-associated fluorescence and produced greater suppression of wound closure than free quercetin, while blank nanoparticles showed minimal cytotoxicity. Together, these findings demonstrate how chitosan and an underexplored plant-derived polysaccharide can be engineered into a functional inhalable nanoplatform, linking aerosol performance with enhanced intracellular delivery and anticancer activity. This proof-of-concept supports further investigation of chitosan–chia nanocarriers for localized lung cancer therapy.