Colorectal cancer, the second prime catastrophic cause of cancer-related mortality worldwide, manifests resistance to standard chemotherapy leading to poor patient outcomes. Mono-terpenoid alcohol geraniol, a cardinal ingredient of many essential oils, is active against various cancers and can induce apoptotic events and trigger oxidative assault in striving against cancer. However, its clinical application is restricted due to its indigent bioavailability and non-specific biodistribution. To address these issues, the present study focuses on the fabrication and characterizations of folate receptor-targeted and pH-tunable dextran-modified geraniol protein nano-scaffold (GER-BSA-DEX-F NPs) to instigate oxidative stress and apoptotic effectiveness against HCT-116 colorectal cancer cells. The formulated spherical nano-structure was 117.8 nm in diameter with high encapsulation efficiency and better drug loading capacity. Adequate uptake of GER-BSA-DEX-F NPs in HCT-116 cells and pH-tunable intracellular release of geraniol prompted enhanced cytoplasmatic reactive oxygen species generation that effectuating oxidative stress persuaded apoptosis in HCT-116 cells. GER-BSA-DEX-F NPs caused the decline in mitochondrial membrane potential and executed loss of micro-tubular organization in HCT-116 cells. This ultimately impelled apoptosis-inducing cell death by arresting the cell cycle at the G2/M phase. In conclusion, these findings divulge that GER-BSA-DEX-F NPs may be a striking therapeutic strategy against colorectal cancer therapy.

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http://dx.doi.org/10.1016/j.ijbiomac.2025.141741DOI Listing

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