KRAS mutant colon cancer-targeted induction of ferroptosis via photocatalytic activation of BiVO4-embedded silica nano with cascadic downregulation of GPX4/xCT axis.
10.1016/j.apsb.2025.06.024
- Author:
Yixin JIANG
1
;
Ratchapol JENJOB
1
;
Dahee RYU
1
;
Zheyu SHEN
2
;
Su-Geun YANG
1
Author Information
1. Department of Biomedical Science, BK21 FOUR Program in Biomedical Science and Engineering, Inha University College of Medicine, Incheon 22212, Republic of Korea.
2. School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China.
- Publication Type:Journal Article
- Keywords:
Benzoyl ferrocene;
BiVO4 nanoparticles;
CD44 targeting peptide;
Ferroptosis;
GPX4/xCT axis;
KRAS mutant colon cancer;
Photocatalysis;
Sorafenib
- From:
Acta Pharmaceutica Sinica B
2025;15(9):4932-4944
- CountryChina
- Language:English
-
Abstract:
Kirsten rat sarcoma virus (KRAS) is a common oncogene in human cancers. Approximately 40% of the patients diagnosed with colorectal cancer (CRC) have KRAS mutations that exhibit strong resistance to targeted molecular therapy and EGFR antibody treatment. In this study, we present photocatalytic silica nanoparticles (A6-FS/BiVO4 DMSNs) for targeted therapy of KRAS mutant CRC with the induction of cascadic ferroptosis events. Dendritic mesoporous silica nanoparticles (DMSNs) were impregnated with photocatalytic BiVO4, loaded with ferroptotic agents (benzoyl ferrocene: B and sorafenib: S), and encoded with CD44-targeting A6 peptides. For the targeting design, we observed CD44 overexpression in KRAS mutant CRC cells using CPTAC data analysis. Upon laser irradiation, A6-FS/BiVO4 DMSNs generate electron-hole pairs (e-/h+), which produce hydroxyl radical (OH·) and superoxide anions (O2 · -). Laser irradiation simultaneously initiates the dissociation of iron (Fe2+) from benzoyl ferrocene and the release of sorafenib. This cascade induces ferroptosis in KRAS mutant CRC cells, especially under conditional inhibition of redox-regulating proteins (cystine/glutamate antiporter and glutathione peroxidase 4), and significantly inhibits tumor growth in a KRAS mutant CRC xenograft animal model.
