Switching Apoptosis to Ferroptosis: Metal–Organic Network for High-Efficiency Anticancer Therapy

TLDR

Advanced materials that regulate cell death, particularly ferroptosis, are essential for developing new anticancer therapies. The study designs MON‑p53, a metal–organic network carrying a p53 plasmid, to eradicate cancer cells via a ferroptosis/apoptosis hybrid pathway. MON‑p53 combines p53 plasmid delivery with a Fenton‑reaction‑inducing metal–organic network to trigger oxidative stress and ferroptosis. In a 75‑day mouse study, MON‑p53 induced ferroptosis, produced a bystander effect, suppressed tumor growth, extended survival, and reduced blood, lung, and liver metastasis.

Abstract

Discovering advanced materials for regulating cell death is of great importance in the development of anticancer therapy. Herein, by harnessing the recently discovered oxidative stress regulation ability of p53 and the Fenton reaction inducing capability of metal–organic network (MON), MON encapsulated with p53 plasmid (MON-p53) was designed to eradicate cancer cells via ferroptosis/apoptosis hybrid pathway. After confirming the detailed mechanism of MON-p53 in evoking ferroptosis, we further discovered that MON-p53 mediated a "bystander effect" to further sensitize cancer cells toward the MON-p53 induced ferroptosis. A 75-day anticancer experiment indicated that MON-p53 treatment not only suppressed the tumor growth but also prolonged the life-span of tumor bearing mice. Owing to its ability to promote intracellular oxidative stress, MON-p53 decreased the blood metastasis, lung metastasis, and liver metastasis. As a consequence, discovering methods to induce cell ferroptosis would provide a new insight in designing anticancer materials.