Mechanism of Self-Assembled Celastrol-Erianin Nanomedicine for treatment of breast cancer

Abstract

Apoptosis as a common form of programmed cell death, plays a crucial role in tumor therapy. Celastrol and erianin are natural compounds extracted from plants. Celastrol exhibits cytotoxic effects on various tumor cells through mechanisms such as ferroptosis and apoptosis, while erianin significantly inhibits the growth and metastasis of cancer cells. However, the high toxicity of celastrol and the low water solubility of both compounds hinder their clinical applications. In this study, nanoparticles (CEN) self-assembled from celastrol and erianin were designed to enhance drug solubility and tumor-targeting capability. These nanoparticles significantly inhibited the proliferation of tumor cells while effectively killing the entire tumor cell population. Additionally, using activity-based protein profiling (ABPP) and a celastrol-probe (cel-p), Annexin A2 was identified as the target of celastrol in 4 T1 cells. Proteomics was subsequently used to evaluate the changes in protein expression induced by CEN. In a mouse model of breast cancer, CEN demonstrated superior tumor-targeting ability and prolonged action due to the enhanced permeability and retention (EPR) effect, resulting in better therapeutic efficacy with lower systemic toxicity. In conclusion, this study provides a novel reference for the treatment of breast cancer.