Targeting ferroptosis induction via nanomaterials in hepatocellular carcinoma: an insight into mechanism and therapeutic potential.

Authors

Yang Song, Shasha Yu, Fengshou Chen, Yizi Wang, Haishan Zhang, Xiaohan Qu

Published in

Journal of nanobiotechnology. Jun 26, 2026. Epub Jun 26, 2026.

Abstract

Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, continues to be a leading cause of cancer-related deaths worldwide, despite the development of new treatment options, including systemic regimens, locoregional treatments, transplantation, and resection. Significant etiological and genetic heterogeneity, an immunosuppressive tumor microenvironment, dose-limiting toxicities, and high rates of post-treatment recurrence continue to inhibit robust responses. Given the crucial role of the liver in iron metabolism and oxidative homeostasis, ferroptosis-a controlled, iron-dependent cell death triggered by glutathione depletion, GPX4 inactivation, and lipid peroxidation, has become a potential therapeutic vulnerability in HCC. However, the risk of off-target oxidative damage, insufficient intratumoral transport, and the poor solubility and pharmacokinetics of small-molecule ferroptotic inducers limit the therapeutic application of ferroptosis induction.The current review is novel to the best of our knowledge, focusing on a targeted and current synthesis of nanomaterials delivering ferroptotic inducers in order to induce ferroptosis in HCC as a next-generation therapeutic paradigm. We describe how constructed nanoplatforms allow for spatiotemporally controlled ROS formation and iron-catalyzed lipid peroxidation, while also improving tumor-selective accumulation of ferroptosis triggers, extending circulation, and improving stability. In order to transform ferroptotic stress into antitumor immunity, we highlight ferroptotic inducing nanomaterials that co-deliver ferroptosis inducers alongwith chemotherapeutics or photothermal/photodynamic agents, and immunomodulatory designs that invoke innate immune pathways like cGAS-STING. This work establishes ferroptosis-inducing nanomedicine as a new and quickly developing field with the potential to overcome resistance, expand therapeutic windows, and enhance long-term outcomes for patients with HCC.

PMID:
42351148
Bibliographic data and abstract were imported from PubMed on 26 Jun 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.