Papain bioinspired gold nanoparticles augmented the anticancer potency of 5-FU against lung cancer

Lung cancer is one of the most widely recognised types of cancer and the acquisition of resistance towards chemotherapeutic drugs worsens the situation. Therefore, a site-directed, multi-targeting drug delivery system that is compliant with patients is the need of the hour. 5-Fluorouracil (5-FU), an anti-cancer chemotherapy drug, was delivered to the lung cancer cells using papain-inspired gold nanoparticles (PpGNPs) as the drug delivery system. Papain is anti-cancer by nature; hence, it rendered this anti-cancer property to the PpGNPs as well. This bio-conjugation of 5-FU and PpGNPs worked synergistically and more efficiently in combating lung cancer. The synthesis, stability, and the size of the PpGNPs, and their bio-conjugation with 5-FU (5F-PpGNPs), were confirmed by different physical techniques: for example, UV-Vis spectroscopy, TEM, DLS, and estimation of the zeta potential. The drug-loading efficiency of 5-FU in 5F-PpGNPs was confirmed and validated by UV-Vis spectroscopy. The efficacy of 5F-PpGNPs (IC50 11.7 mu g/mL) against human lung cancer A549 cell line was found to have improved significantly over that of pure 5-FU (IC50 25.6 mu g/mL). However, the 5F-PpGNPs did not show any significant toxicity (even up to a fairly high concentration) towards normal mouse embryonic fibroblasts cell line (3T3-L1). The apoptotic effects, nuclear condensation, ROS generation, and the loss of mitochondrial membrane potential (Delta psi m) of 5F-PpGNPs were analysed. The results clearly showed that conjugation with papain-inspired gold nanoparticles (5F-PpGNPs) significantly augmented the potency of 5-FU by acting synergistically. Thus, the enhanced anti-proliferating effect of 5F-PpGNPs over that of the pure drug would be an important step that will help to overcome the resistance of chemotherapeutic drugs towards lung cancer cells and prove to be of great advantage during lung cancer treatment.