Ursolic Acid-Loaded Iron-MOF Nanomedicine Inhibits Lung Cancer Metastasis via JAK2/STAT3 Suppression and Ferroptosis.

Abstract

Lung cancer metastasis is the primary cause of patient mortality, underscoring an urgent need for highly effective and low-toxicity therapies. Ursolic acid (UA), a natural triterpenoid, possesses potent antitumor activity, yet its clinical translation has been hindered by poor water solubility, low bioavailability, and nonspecific distribution. To overcome these limitations, we developed a UA-loaded iron-based metal-organic framework (MOF) nanomedicine, termed Ursolic Acid-loaded Iron-MOF (UA@MOF). Harnessing the high surface area and tunable porosity of MOFs, this system enables efficient UA encapsulation and promotes tumor-targeted delivery through the enhanced permeability and retention (EPR) effect. Once internalized, UA suppresses the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) signaling pathway, while iron ions released from the MOF induce ferroptosis in tumor cells via Fenton reactions. Together, these dual mechanisms act synergistically to inhibit tumor growth and metastasis. This work presents a novel strategy to improve the delivery and efficacy of natural antitumor agents, offering promising potential for the treatment of metastatic lung cancer.