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Enzyme-responsive biomimetic ferritin nanoparticles for selective cancer therapy
Xiaohan Hao1, Hao Zhang2, Yuzhao Yang1
1School of Medicine, South China University of Technology, Guangzhou, 510006, People's Republic of China.
Biomaterials
|July 24, 2025
Summary
This study introduces a novel nanoplatform that selectively activates cancer-killing peptides within tumors, overcoming toxicity issues. This approach shows promise for effective cancer treatment with reduced side effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Plasma membrane rupture is a potential cancer therapy but limited by non-selective toxicity, especially hemolysis.
- Current approaches lack specificity, leading to side effects during systemic administration.
Purpose of the Study:
- To develop a biomimetic nanoplatform for enzyme-mediated activation of natural cytolytic peptides (NCPs) specifically within tumor microenvironments.
- To engineer nanoparticles that remain inactive in circulation and are selectively reactivated at tumor sites, minimizing systemic toxicity.
Main Methods:
- Biomimetic ferritin nanoparticles (MMFn) were engineered with NCPs, an MMP-2/9-responsive peptide, and human ferritin (HFn).
- MMFn were tested in vitro on MCF-7-TamR cells and in vivo on various xenograft models (colorectal, pancreatic, drug-resistant breast cancer, PDX).
- Cellular effects (p38, mTOR, PD-L1) and in vivo tumor targeting, antitumor immunity, and systemic toxicity were evaluated.
Main Results:
- MMFn demonstrated selective activation within tumor microenvironments, upregulating p38 and downregulating mTOR and PD-L1 in cancer cells.
- Significant tumor targeting and robust antitumor immunity were observed in multiple xenograft models.
- No systemic toxicity was detected, indicating a favorable safety profile.
Conclusions:
- The "deactivation-reactivation" strategy using MMFn effectively addresses tumor resistance and reprograms immunosuppressive tumor microenvironments.
- This biomimetic nanoplatform offers a potent and safe therapeutic approach for diverse malignancies by enabling targeted cancer cell membrane disruption.
