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Parallel Lipid Peroxide Accumulation Strategy Based on Bimetal-Organic Frameworks for Enhanced Ferrotherapy
Hao Xin1, Fang Wang1, Rengan Luo1
1State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|December 30, 2020
Summary
This study introduces a novel strategy using metal-organic frameworks (MOFs) to enhance ferroptosis therapy. The MOFs promote parallel lipid peroxide accumulation, effectively inhibiting tumor growth in mice.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- Ferroptosis is a nonapoptotic cell death pathway crucial for cancer therapy.
- Current ferroptosis strategies often focus on single mechanisms like lipid peroxidation or glutathione depletion.
- Developing synergistic approaches is key to overcoming treatment resistance in apoptosis-insensitive tumors.
Purpose of the Study:
- To design a parallel lipid peroxide accumulation strategy for enhanced ferroptosis therapy.
- To utilize catalytic metal-organic frameworks (MOFs) for controlled release of ferroptosis inducers and amplification of oxidative stress.
- To investigate the efficacy of this strategy in inhibiting tumor growth.
Main Methods:
- Synthesis of a bimetallic MOF using iron porphyrin linkers and cupric ion nodes.
- Encapsulation of erastin (a ferroptosis inducer) within the MOF layers using disulfide spacers.
- Demonstration of glutathione-responsive erastin release in a tumor microenvironment.
- Evaluation of MOF-induced dual Fenton reactions for hydroxyl radical generation and lipid peroxide accumulation.
- Assessment of tumor growth inhibition in live mice.
Main Results:
- The designed MOF system successfully released erastin in a glutathione-rich tumor microenvironment.
- Exfoliated MOFs acted as dual Fenton reaction inducers, generating hydroxyl radicals and promoting lipid peroxide accumulation.
- Erastin-induced glutathione depletion inhibited glutathione peroxidase 4, further enhancing lipid peroxide buildup.
- The parallel lipid peroxide accumulation strategy significantly inhibited tumor growth in vivo.
- The approach demonstrated potential for treating apoptosis-insensitive tumors.
Conclusions:
- A novel parallel lipid peroxide accumulation strategy based on catalytic MOFs was successfully established for enhanced ferroptosis.
- This strategy synergistically combines controlled inducer release, amplified oxidative stress, and inhibited antioxidant defense.
- The developed MOF system shows significant promise for treating apoptosis-resistant cancers and warrants further investigation.
