Double coordination-driven Fe-DOX synergy enhances ferroptosis and immunogenic cancer therapy.
- 1Department of Applied Life Science, BK21 Program, Research Institute of Inflammatory Disease (RID), Konkuk University, Chungju 27478, Republic of Korea.
- 2Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02453, Republic of Korea.
Abstract
Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, has emerged as a potential therapeutic strategy for cancer. However, intrinsic resistance, off-target toxicity, and poor redox efficiency limit the effectiveness of existing ferroptosis-inducing platforms. This study reports novel heparin-derived metal coordination nanoparticles (HDMC NP) that leverage catechol-metal-drug coordination chemistry to enhance ferroptosis and immunogenic cell death (ICD). In this self-assembled supramolecular system, doxorubicin (DOX) directly coordinates to Fe³⁺ centers established by catechol-Fe³⁺ interactions on the heparin backbone, forming a stable HDMC NP with high drug-loading efficiency. This coordination not only stabilizes the complex under neutral conditions but also triggers disassembly in response to pH changes in the tumor microenvironment. Notably, the DOX-Fe³⁺ pairing supports sustained redox activity, amplifying ROS production and ferroptotic stress in a coordination-dependent manner beyond the effect of either component alone. In animal models, HDMC NP suppresses tumor growth by inducing both ferroptosis and ICD, characterized by calreticulin exposure and CD8⁺ T cell infiltration. Collectively, this platform provides a redox-active nanotherapeutic based on coordination-defined assembly with potential for broad applications in metal-ion modulated diseases.
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BibTeX
@article{ma2026double,
title = {{Double coordination-driven Fe-DOX synergy enhances ferroptosis and immunogenic cancer therapy.}},
author = {Gaeun Ma and Yun-Hwa Jeong and Yeonsu Ryu and Jae-Hyeon Lee and Seong-Bin Yang and Byeong-Kook Hwang and Jeong Uk Choi and Jooho Park},
journal = {Acta pharmaceutica Sinica. B},
year = {2026},
month = jun,
doi = {10.1016/j.apsb.2026.06.006},
url = {https://europepmc.org/article/MED/42948409},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Double coordination-driven Fe-DOX synergy enhances ferroptosis and immunogenic cancer therapy.
AU - Gaeun Ma
AU - Yun-Hwa Jeong
AU - Yeonsu Ryu
AU - Jae-Hyeon Lee
AU - Seong-Bin Yang
AU - Byeong-Kook Hwang
AU - Jeong Uk Choi
AU - Jooho Park
PY - 2026
DA - 2026/06/08
JO - Acta pharmaceutica Sinica. B
DO - 10.1016/j.apsb.2026.06.006
UR - https://europepmc.org/article/MED/42948409
AB - Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, has emerged as a potential therapeutic strategy for cancer. However, intrinsic resistance, off-target toxicity, and poor redox efficiency limit the effectiveness of existing ferroptosis-inducing platforms. This study reports novel heparin-derived metal coordination nanoparticles (HDMC NP) that leverage catechol-metal-drug coordination chemistry to enhance ferroptosis and immunogenic cell death (ICD). In this self-assembled supramolecular system, doxorubicin (DOX) directly coordinates to Fe³⁺ centers established by catechol-Fe³⁺ interactions on the heparin backbone, forming a stable HDMC NP with high drug-loading efficiency. This coordination not only stabilizes the complex under neutral conditions but also triggers disassembly in response to pH changes in the tumor microenvironment. Notably, the DOX-Fe³⁺ pairing supports sustained redox activity, amplifying ROS production and ferroptotic stress in a coordination-dependent manner beyond the effect of either component alone. In animal models, HDMC NP suppresses tumor growth by inducing both ferroptosis and ICD, characterized by calreticulin exposure and CD8⁺ T cell infiltration. Collectively, this platform provides a redox-active nanotherapeutic based on coordination-defined assembly with potential for broad applications in metal-ion modulated diseases.
SN - 2211-3835
SN - 2211-3843
ER -