Abstract
Contemporary challenges in chemotherapy for triple negative breast cancer (TNBC) are inadequate specificity towards malignant cells, constraints imposed by dose-related toxicities, and side effects on normal cells. To address these bottlenecks, our study introduces, a drug-free “trojan horse-like” folate functionalized, L-arginine-coated ceria (FA-L-arg-CeO2) nanoplatform for treating metastatic TNBC. We show that this engineered nanozyme exhibiting enhanced surface oxygen vacancies (VO●) facilitated band structure reconstruction and amplified the photothermal/photodynamic therapeutic (PTT/PDT) efficacy under single laser irradiation (808 nm) through reactive oxygen species (ROS) production, thereby outperforming the surface defect-free commercial nano-CeO2 in rapid tumour ablation (86% in 48 h). This low-cost targeted therapy facilitated substantial folate receptor-mediated endocytosis and accumulation of the biostable nanozymes in MDA-MB-231 cells (84% in 48 h). These drug-free VO●-rich FA-L-arg-CeO2 nanostructures were found to exhibit distinctive pH-active multi-enzyme mimicking characteristics, imparting exceptional therapeutic potential and effectively inhibited cell metastasis (62% within 12 h). Mechanistically, we observed that electrons generated at the VO●-rich surface during laser irradiation modulate the pH-responsive intracellular redox balance, synergistically killing the MDA-MB-231 cancer cells and safeguarding the benign L929 cells. Unlike drug-loaded CeO2-based nanoplatforms, the nanozymes protected the healthy cells from radiation damage through photo-triggered-ROS scavenging by mimicking catalase. This novel, drug-free nanozyme-based therapy leads the way for smart, bio-inspired multi-modal cancer treatments, ensuring enhanced efficacy and bio-safety.