Du Yongzhong's research group of the School of Pharmacy of Zhejiang University reported in Advanced Materials that ferritin targeted prodrugs are used for...

Iron death is an iron-dependent form of regulatory cell death characterized by the accumulation of lipid peroxidation (LPO) and has great
potential as a new cancer treatment strategy.
Existing research suggests that LPO production results from a biologically mediated Fenton reaction that catalyzes endogenous _H2O2 Convert to ? OH, which is one of
the most toxic ROS.
Therefore, intracellular iron is the basis of
iron death.
With the development of nanotechnology, various iron-based nanomaterials, such as iron oxide nanoparticles, amorphous iron nanoparticles, and iron-organic frameworks, have shown tantalizing therapeutic advantages
due to their ability to deliver exogenous iron to activate tumor iron death.
However, excessive use of exogenous metals can cause potential adverse effects on human health, including acute and chronic damage
.
Therefore, there is an urgent need to develop an alternative method to induce iron death
.

On October 10, 2022, Professor Du Yongzhong's team from the School of Pharmacy, Zhejiang University published a speech entitled " Ferritin-hijacking nanoparticles spatiotemporally directing endogenous Ferroptosis for Synergistic Anticancer Therapy
".
The study performed this study by binding the ferritin homing peptide HKN₁₅ to the photosensitizer dihydroporphyrinol e6 (Ce6), without the introduction of Fenton reactive metals.
A ferritin-hijacking nanoparticle (Ce6-PEG-HKN₁₅) was prepared for endogenous iron death to achieve safe and efficient treatment of
tumors.

The research team constructed carrier-free prodrug nanoparticles (Ce6-PEG-HKN₁₅ NP) through a self-assembly strategy, which can be targeted to aggregate around
ferritin after being internalized by tumor cells.
Under near-infrared light, Ce6 can be activated and reactive oxygen species (ROS)
can be effectively released.
Rich ROS can not only mediate ferritin destruction, promote internal iron release, activate endogenous iron death, but also can directly kill tumor cells
.
In addition, excess _H2O2 within cells is converted to O catalyzed by the Fenton reaction ₂.
Further enhance the photodynamic effect, destroy the antioxidant defense of tumors, and amplify oxidative stress damage
.
The results of this study show that the destruction of ferritin through spatiotemporal destruction can effectively activate endogenous iron death, which provides new inspiration
for iron death-photodynamic synergistic antitumor therapy.

Schematic diagram of ferritin-targeted prodrug nanoparticles and their anti-tumor mechanisms for synergistic PDT and iron death therapy

The first author of this paper is Zhu Luwen, a doctoral student at the School of Pharmacy, Zhejiang University, Professor Ji Jiansong, School of Medicine, Zhejiang University, Professor Du Yongzhong, School of Pharmacy, Zhejiang University, and Xu Xiaoling, associate researcher of Zhejiang Shuren University
.
This project is supported
by the National Key R&D Program of China and the Natural Science Foundation of Zhejiang Province.

Original link: https://doi.
org/10.
1002/adma.
202207174