Abstract P68: Photocatalytic Ferroptosis Induction in KRAS-Mutant CRC via BiVO4-Silica Nanoparticles
Jun-hyeon Park, Young-rok Choi, Yoon-hee Shim, Da-hee Ryu, Truong Ngoc Thuan, Arjaree Jobdeedamrong, Su-Geun YangAbstract
Purpose:
KRAS mutations are prevalent in colorectal cancer (CRC) and are associated with resistance to conventional therapies. Recent studies suggest that KRAS-mutant cancers exhibit increased vulnerability to ferroptosis, a non-apoptotic form of cell death driven by iron-dependent lipid peroxidation. In this study, we aimed to develop a novel nano-based therapeutic strategy to selectively induce ferroptosis in KRAS-mutant CRC cells via photocatalytic activation.
Method:
We synthesized BiVO4-embedded mesoporous silica nanoparticles (BiVO4@SiO2 NPs) capable of generating reactive oxygen species (ROS) under visible light irradiation. The particles were functionalized with a KRAS-targeting peptide to enhance specificity. Upon irradiation, the BiVO4 core catalyzed ROS production, triggering a cascade that downregulated the GPX4/xCT axis, crucial regulators of ferroptosis defense. In vitro experiments were performed on KRAS-mutant and wild-type CRC cell lines, and in vivo efficacy was tested using a KRAS-mutant xenograft mouse model.
Result:
Photocatalytic activation of BiVO4@SiO2 NPs led to a significant accumulation of intracellular ROS and lipid peroxides in KRAS-mutant cells, resulting in ferroptosis-specific cell death. The GPX4 and xCT protein levels were markedly reduced upon treatment, confirming the cascadic suppression of ferroptosis-inhibitory pathways. In vivo, the targeted nanoparticles significantly inhibited tumor growth without observable systemic toxicity.
Conclusion:
Our findings demonstrate that photocatalytically activated BiVO4@SiO2 nanoparticles can selectively induce ferroptosis in KRAS-mutant CRC through targeted downregulation of the GPX4/xCT axis. This nanoferroptosis strategy presents a promising and precise therapeutic avenue for treating therapy-resistant KRAS-mutant colorectal cancers.
Acknowledgement:
This work was supported by the NRF of Korea, funded by the Ministry of Education and MSIT (RS-2023-00208587, RS-2024-00440714, 2018R1A6A1A03025523, RS-2024-00410258).
Citation Format:
Jun-hyeon Park, Young-rok Choi, Yoon-hee Shim, Da-hee Ryu, Truong Ngoc Thuan, Arjaree Jobdeedamrong, Su-Geun Yang. Photocatalytic Ferroptosis Induction in KRAS-Mutant CRC via BiVO4-Silica Nanoparticles [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P68.