Targeting HSP90AA1 to overcome multiple drug resistance in breast cancer using magnetic nanoparticles loaded with salicylic acid

Ou Chen; Linlin Fu; Yu Wang; Jinggui Li; Jun Liu; Yanqing Wen

doi:10.1016/j.ijbiomac.2024.139443

Targeting HSP90AA1 to overcome multiple drug resistance in breast cancer using magnetic nanoparticles loaded with salicylic acid

Int J Biol Macromol. 2025 Jan 3:139443. doi: 10.1016/j.ijbiomac.2024.139443. Online ahead of print.

Authors

Ou Chen¹, Linlin Fu², Yu Wang³, Jinggui Li⁴, Jun Liu⁵, Yanqing Wen⁶

Affiliations

¹ Department of clinical laboratory, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
² Neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
³ Department of Pharmacy, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
⁴ Liaoning Jiahe Hospital of Traditional Chinese Medicine, Medical Imaging Center, Shenyang, China.
⁵ Department of cardiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China. Electronic address: [email protected].
⁶ Department of Pharmacy, The Fourth Affiliated Hospital of China Medical University, Shenyang, China. Electronic address: [email protected].

PMID: 39756742
DOI: 10.1016/j.ijbiomac.2024.139443

Abstract

Multiple drug resistance (MDR) remains a major obstacle in effective breast cancer chemotherapy. This study explores the role of HSP90AA1 in driving MDR and evaluates the potential of magnetic nanoparticles (Fe₃O₄@SA) loaded with salicylic acid (SA) to counteract drug resistance. A comprehensive screening of 200 SA-related target genes identified nine core genes, including HSP90AA1. Pharmacophore analysis revealed that SA interacts with HSP90AA1, a key regulator of mitochondrial K⁺ channels. Fe₃O₄@SA nanoparticles demonstrated efficient cellular uptake and lysosomal escape, markedly improving the chemosensitivity of resistant breast cancer cells and promoting apoptosis. In vivo experiments further confirmed the anticancer efficacy of Fe₃O₄@SA, highlighting its potential as a promising therapeutic strategy to overcome MDR in breast cancer.

Keywords: Breast cancer; HSP90AA1; Magnetite nanoparticle; Mitochondrial K(+) channels; Multiple drug resistance; Salicylic acid.