Self-propelled protein-based nanomotors enhance cancer therapy by inducing ferroptosis

Limited penetration depth into tumor tissues continues to hinder the development of nanotherapeutics for cancer treatment. A novel self-propelled ferroptosis nanoinducer developed by Southern Medical University was able to achieve deeper penetration into tumor tissues while remaining biocompatible. The work, published in the International Journal of Extreme Manufacturing, lays the groundwork for developing biocompatible, multifunctional nanotherapeutics for cancer treatment.

“Conventional nanoplatforms cannot achieve active penetration, leading to poor penetration depth and efficiency into tumor tissues,” said Yingfeng Tu, the corresponding author on the paper and a professor at the School of Pharmaceutical Sciences, Southern Medical University. “It might weaken the tumor inhibitory effect of the nanoplatform. Here we’re saying, why not design a nanotherapeutic that can actively penetrate deeper into tumor tissues via enhanced diffusion?”

Ferroptosis, a newly defined form of programmed cell death, plays a crucial regulatory role in tumor development. Therefore, researchers have recently developed ferroptosis-based nanoplatforms as a strategy for cancer treatment, but these approaches are still limited by poor biocompatibility, shallow tumor penetration, and low active pharmaceutical ingredient (API) loading.

To address these issues, Tu and coworkers used glutaraldehyde as a crosslinking agent to fabricate active nanoparticles consisting of only two endogenous proteins: glucose oxidase and ferritin. The resulting self-propelled nanotherapeutics exhibited enhanced diffusion, enabling deeper penetration into tumor tissues.

Through the synergistic effect of the two components, intracellular ferroptosis was induced, leading to cell membrane disruption and the simultaneous destruction of multiple tumor cell organelles.

The researchers spent two years on a comprehensive study of their self-propelled ferroptosis nanoinducer, assessing its characterization, motion behavior and chemotactic behavior. Additionally, they evaluated tumor inhibitory performance of the developed nanotherapeutic both in vitro and in vivo.

“Biocompatibility is an issue that deserves greater attention,” said corresponding author Yingfeng Tu. “With the pure-protein framework, potential systemic toxicity can be minimized. The self-propelled nanotherapeutic we developed is capable of deeper tumor penetration with negligible toxicity at the same time. We believe this platform holds strong potential for cancer treatment.”

The researchers are continuing the work, hoping to verify its tumor inhibitory effects on other cancer types, including non-small cell lung cancer. They are dedicated to facilitating its translation from bench to bedside.