2. Academic Validation
  3. High Intensity Focused Ultrasound-Driven Nanomotor for Effective Ferroptosis-Immunotherapy of TNBC

High Intensity Focused Ultrasound-Driven Nanomotor for Effective Ferroptosis-Immunotherapy of TNBC

  • Adv Sci (Weinh). 2024 Feb 11:e2305546. doi: 10.1002/advs.202305546.
Xiangrong Yu 1,  Xuejing Li 2,  Qingwang Chen 3,  Siyu Wang 2,  Ruizhe Xu 2,  Ying He 2,  Xifeng Qin 2,  Jun Zhang 4,  Wuli Yang 5,  Leming Shi 3,  Ligong Lu 1,  Yuanting Zheng 3,  Zhiqing Pang 2,  Shaojun Peng 1
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, P. R. China.
  • 2 Key Laboratory of Smart Drug Delivery, School of Pharmacy, Fudan University, Shanghai, 201203, P.R. China.
  • 3 State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, 2005 Songhu Road, Shanghai, 200438, P.R. China.
  • 4 Department of Radiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.
  • 5 State Key Laboratory of Molecular Engineering of Polymers & Department of Macromolecular Science, Fudan University, Shanghai, 200433, China.
PMID: 38342612 DOI: 10.1002/advs.202305546
Abstract

The heterogeneity of triple-negative breast cancers (TNBC) remains challenging for various treatments. Ferroptosis, a recently identified form of cell death resulting from the unrestrained peroxidation of Phospholipids, represents a potential vulnerability in TNBC. In this study, a high intensity focused ultrasound (HIFU)-driven nanomotor is developed for effective therapy of TNBC through induction of Ferroptosis. Through bioinformatics analysis of typical ferroptosis-associated genes in the FUSCCTNBC dataset, gambogic acid is identified as a promising Ferroptosis drug and loaded it into the nanomotor. It is found that the rapid motion of nanomotors propelled by HIFU significantly enhanced tumor accumulation and penetration. More importantly, HIFU not only actuated nanomotors to trigger effective Ferroptosis of TNBC cells, but also drove nanomotors to activate ferroptosis-mediated antitumor immunity in primary and metastatic TNBC models, resulting in effective tumor regression and prevention of metastases. Overall, HIFU-driven nanomotors show great potential for ferroptosis-immunotherapy of TNBC.

Keywords

ferroptosis; gambogic acid; high intensity focused ultrasound; immunotherapy; nanomotors; triple-negative breast cancers.

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