Citation: Shao-Qi Guan, Chen-Hui Liu, Ya-Ping Wang, Xiao-Dong Zhang, Zhong-Min Cao, Mei Pan. Cancer cell membrane-biomimetic metallacycles for tumor microenvironment-responsive ferroptosis/apoptosis therapy with low systemic toxicity[J]. Chinese Chemical Letters, ;2026, 37(7): 111692. doi: 10.1016/j.cclet.2025.111692 shu

Cancer cell membrane-biomimetic metallacycles for tumor microenvironment-responsive ferroptosis/apoptosis therapy with low systemic toxicity

Shao-Qi Guan ^a ,
Chen-Hui Liu ^a ,
Ya-Ping Wang ^{a, b, *,} ,
Xiao-Dong Zhang ^a ,
Zhong-Min Cao ^a ,
Mei Pan ^{a, *,}

a.
MOE Laboratory of Bioinorganic and Synthetic Chemistry, Lehn Institute of Functional Materials, IGCME, GBRCE for Functional Molecular Engineering, School of Chemistry, Sun Yat-sen University, Guangzhou 510275, China
b.
Department of Radiology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510030, China

wangyp83@mail.sysu.edu.cn

panm@mail.sysu.edu.cn

Received Date: 25 April 2025
Revised Date: 3 August 2025
Accepted Date: 8 August 2025
Available Online: 9 August 2025

Figures(5)

Ferroptosis, a form of programmed cell death driven by iron-dependent lipid peroxidation (LPO), has emerged as a promising therapeutic strategy for cancer. However, challenges such as uncontrolled iron delivery, insufficient ferroptosis induction efficiency, and off-target drug leakage limit its applications. To address these limitations, we developed a biomimetic nanoplatform (Fe-DTX@M) integrating cancer cell membrane-camouflaged Fe-based metallacycles with the chemotherapeutic drug docetaxel (DTX), which synergistically amplifies ferroptosis and apoptosis for precise and effective cervical cancer therapy. The membrane camouflage enabled highly efficient tumor-specific accumulation, achieving a 5.4-fold increase compared to non-targeted controls, and reduced systemic toxicity. Within tumors, Fe²⁺/Fe³⁺ cycles attributed to Fe-based metallacycle drove Fenton reactions to convert H₂O₂ into ^•OH, inducing LPO, while Fe³⁺-mediated glutathione depletion inhibited GPX4, amplifying ferroptosis with 2.4-fold malondialdehyde (MDA) increase. Acid-triggered DTX release of nanoplatform further promoted apoptosis, thereby enhancing therapeutic efficacy. Furthermore, Fe-DTX@M exhibited excellent long-term biocompatibility and safety in normal mice over 30 days post-intravenous injection. This combination of biomimetic metallacycles-induced ferroptosis and chemotherapy-induced apoptosis may provide a new paradigm for achieving effective cancer therapy.
- Metallacycles,
- Cancer cell membrane,
- Homologous targeting,
- Ferroptosis,
- Tumor microenvironment
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