Novel protocatechuic acid encapsulated bovine serum albumin functionalized folic acid nanoparticles for targeted therapy in urethane-induced lung cancer model

Lung cancer mortality rates are rising globally, increasing the need for innovative, natural compounds with fewer side effects. Protocatechuic acid (PCA) is a natural phenolic compound with cytotoxic effects against human lung cancer cells, but its poor water solubility limits its use. We hypothesized that encapsulating PCA within bovine serum albumin (BSA) nanoparticles would enhance its solubility compared to previous PCA-loaded-nanocarriers. So, we encapsulated PCA within BSA-nanoparticles conjugated with folic acid (FA) and evaluated its targeting efficacy in lung cancer cell line and lung cancer mouse model. The resulting nanocomposite (PCA-BSA@FA-NPs) had a 229 nm size. Our in vitro study indicated that PCA-BSA@FA-NPs demonstrated a 92.03% reduction in toxicity compared to doxorubicin, and a 59.67% reduction compared to PCA when tested against normal WI38 cells. In the lung cancer mouse model, the NF-κB expression decreased by 179% in the PCA-BSA@FA-NPs-treated group compared to the PCA-treated group. Both groups showed significant reductions in MAPK and FAK, with greater declines of 172% for MAPK and 316% for FAK in the PCA-BSA@FA-NPs-treated group. In conclusion, PCA-BSA@FA-NPs may serve as a promising therapy for targeting lung cancer with reduced toxicity.