Induction of Non-Canonical Ferroptosis by Targeting Clusters Suppresses Glioblastoma
Kai Cao,
Liyuan Xue,
Kaidi Luo,
Wendi Huo,
Panpan Ruan,
Dongfang Xia,
Xiuxiu Yao,
Wencong Zhao,
Liang Gao,
Xueyun Gao
Affiliations
Kai Cao
Center of Excellence for Environmental Safety and Biological Effects, Department of Chemistry, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China
Liyuan Xue
Center of Excellence for Environmental Safety and Biological Effects, Department of Chemistry, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China
Kaidi Luo
Center of Excellence for Environmental Safety and Biological Effects, Department of Chemistry, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China
Wendi Huo
Center of Excellence for Environmental Safety and Biological Effects, Department of Chemistry, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China
Panpan Ruan
Center of Excellence for Environmental Safety and Biological Effects, Department of Chemistry, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China
Dongfang Xia
Center of Excellence for Environmental Safety and Biological Effects, Department of Chemistry, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China
Xiuxiu Yao
Center of Excellence for Environmental Safety and Biological Effects, Department of Chemistry, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China
Wencong Zhao
Center of Excellence for Environmental Safety and Biological Effects, Department of Chemistry, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China
Liang Gao
Center of Excellence for Environmental Safety and Biological Effects, Department of Chemistry, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China
Xueyun Gao
Center of Excellence for Environmental Safety and Biological Effects, Department of Chemistry, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China
Glioblastoma multiforme (GBM) is the most aggressive brain tumor. There is a pressing need to develop novel treatment strategies due to the poor targeting effect of current therapeutics. Here, a gold cluster coated with optimized GBM-targeting peptide is engineered, namely NA. NA can efficiently target GBM both in vitro and in vivo. Interestingly, the uptake of NA significantly sensitizes GBM cells to ferroptosis, a form of programmed cell death that can bypass the tumor resistance to apoptosis. This effect is exerted through regulating the HO-1-dependent iron ion metabolism, which is the non-canonical pathway of ferroptosis. The combined treatment of a ferroptosis inducer and NA profoundly inhibited tumor growth in both the GBM spheroid model and a syngeneic mouse model with enhanced ferroptosis levels and excellent biosafety. Importantly, the infiltration of tumoricidal lymphocytes is also significantly increased within tumor. Therefore, NA presents a potential novel nanomaterial-based strategy for GBM treatment.
