Novel Nanotheranostic Platform “Ferritin@Vitexin” Reverses Infertility by Halting Ferroptosis in Sperm Cells
A study published in the prestigious journal Advanced Functional Materials unveils a novel nanotheranostic platform, “ferritin@vitexin,” that effectively treats asthenospermia (low sperm motility), a major cause of male infertility. This innovative strategy harnesses a natural plant-derived compound with built-in imaging capabilities to precisely target and inhibit a recently discovered cell death pathway known as ferroptosis in sperm-producing cells.
The research, a collaboration between Sir Run Run Shaw Hospital at Zhejiang University School of Medicine, Guangzhou Medical University, The Chinese University of Hong Kong, Shenzhen, and Hunan Normal University, demonstrates a powerful synergy between natural products and advanced nanotechnology for reproductive medicine.
Addressing a Major Challenge in Male Infertility
Asthenospermia is characterized by reduced sperm motility and is increasingly linked to oxidative stress and dysregulated iron metabolism, which together drive ferroptosis—an iron-dependent form of programmed cell death. Current treatments often lack specificity and efficacy.
A Natural Drug with a Built-In “Glow”: The AIE Phenomenon
The research team turned to Vitexin, a natural flavonoid extracted from plants like the chasteberry, known for its potent antioxidant properties. The key breakthrough was the discovery that Vitexin possesses a unique property called Aggregation-Induced Emission (AIE).
“Unlike traditional fluorescent molecules that dim when clustered, AIEgens like Vitexin light up brightly in their aggregated state,” explained co-corresponding author Professor Fei Sun of Zhejiang University. “This means Vitexin is not only a therapeutic agent but also a self-tracking imaging probe. We call this new paradigm ‘AIE-pharmacology,’ where the drug itself guides its own delivery and reports its bioactivity in real-time.”
An Intelligent Nanocarrier: Precisely Crossing Biological Barriers
To deliver Vitexin directly to its target—the spermatogenic cells within the testes—the researchers encapsulated it within nanocages of human heavy-chain ferritin (HFn). Ferritin, the body’s natural iron-storage protein, can naturally cross the blood-testis barrier by binding to transferrin receptors on testicular cells.
“Our ferritin@vitexin nanoparticle acts like a smart ‘nano-truck’,” said co-corresponding author Professor Xinghua Yu of Zhejiang University. “The truck itself (ferritin) chelates excess toxic iron ions, while its cargo (Vitexin) activates the cellular antioxidant defense system. Together, they launch a precision strike on the ferroptosis pathway from two different angles.”
Robust Therapeutic Efficacy and Clear Mechanism
In a mouse model of asthenospermia induced by the chemotherapeutic agent busulfan, treatment with ferritin@vitexin yielded remarkable results:
Sperm count was restored to nearly 83% of normal levels.
Sperm motility and progressive movement were significantly improved.
Testicular tissue damage was markedly alleviated, with seminiferous tubules regaining healthy architecture.
Mechanistic studies revealed a dual-action mode:
The Ferritin Component elevated levels of ferritin heavy chain 1 (FTH1), effectively sequestering excess labile iron and reducing cellular iron overload.
The Vitexin Component activated the key Nrf2/HO-1 antioxidant pathway and upregulated the core anti-ferroptosis protein, GPX4, thereby suppressing lethal lipid peroxidation.
A New Paradigm for Future Therapeutics
“This work pioneers the application of an intrinsically AIE-active natural product in reproductive medicine,” commented co-corresponding author Professor Ben Zhong Tang of The Chinese University of Hong Kong, Shenzhen, a pioneer in the AIE field. “It not only provides a novel, effective, and biocompatible strategy for treating male infertility but, more importantly, establishes a new theranostic paradigm of ‘Natural AIEgen + Intelligent Nanocarrier,’ paving the way for future therapies against a wide range of ferroptosis-related diseases.”
The research was supported by the Key Research and Development Program of Zhejiang Province and other funding agencies.
About Advanced Functional Materials:
Advanced Functional Materials is a leading international journal publishing groundbreaking research in all aspects of materials science, with a focus on advanced functional and smart materials for cutting-edge applications.