Bioactive glass nanoparticles induce strong preferential cytotoxicity and excessive ROS-mediated oxidative stress and apoptotic genomic DNA damage in non-small lung cancer cells.

Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer and remains the leading cause of cancer-related mortality worldwide. The limited efficacy and high toxicity of current treatment strategies, including chemotherapeutics like doxorubicin, underscore the urgent need for safer, more selective anticancer strategies. Bioactive glass nanoparticles (BGNPs), commonly used for bone regeneration and antimicrobial applications, have recently gained attention for their potential anticancer properties. However, their effects on lung cancer cells, particularly NSCLC, are still not fully understood. The present study consequently was conducted to estimate the therapeutic potential of BGNPs against A549 NSCLC cells. Our findings revealed that BGNPs exert potent, concentration-dependent targeted cytotoxicity toward A549 cancer cells, with a remarkably high selectivity index of 124.31, while causing no observable toxicity in normal human skin fibroblasts under the same conditions. Mechanistic investigations revealed that BGNPs induce significantly greater oxidative stress, DNA damage, mitochondrial dysfunction, and apoptosis in A549 lung cancer cells than those triggered by doxorubicin. Notably, BGNPs treatment led to a pronounced, concentration-dependent increase in reactive oxygen species production, resulting in substantial loss of DNA integrity and collapse of mitochondrial membrane potential, exceeding the effects observed with doxorubicin. These changes were accompanied by marked, concentration-dependent modulation of apoptosis-related gene expression, including significant upregulation of the pro-apoptotic p53 and Bax genes, alongside strong downregulation of the anti-apoptotic Bcl2 gene, in comparison to doxorubicin-treated cells. In conclusion, this study provides compelling evidence that BGNPs possess highly selective, multi-targeted anticancer activity against NSCLC cells, surpassing the efficacy of conventional chemotherapy with doxorubicin. These findings position BGNPs as promising candidates for further development as safe and effective therapeutic agents for lung cancer. Future in vivo studies are essential to validate their clinical potential, either as standalone treatments or in combination with existing therapies.