2. Academic Validation
  3. Co-loaded lapatinib/PAB by ferritin nanoparticles eliminated ECM-detached cluster cells via modulating EGFR in triple-negative breast cancer

Co-loaded lapatinib/PAB by ferritin nanoparticles eliminated ECM-detached cluster cells via modulating EGFR in triple-negative breast cancer

  • Cell Death Dis. 2022 Jun 20;13(6):557. doi: 10.1038/s41419-022-05007-0.
Xinghan Wu  # 1,  Huan Sheng  # 2,  Liping Zhao 2,  Mingxia Jiang 2,  Han Lou 3,  Yue Miao 4,  Ni Cheng 2,  Weifen Zhang 2 5,  Dejun Ding 6 7,  Wentong Li 8 9
Affiliations

Affiliations

  • 1 Department of Pathology, Weifang Medical University, Weifang, 261053, Shandong, China.
  • 2 College of Pharmacy, Weifang Medical University, Weifang, 261053, Shandong, China.
  • 3 School of Clinical Medicine, Weifang Medical University, Weifang, 261053, Shandong, China.
  • 4 Department of Oncology, The Second Affiliated Hospital of Shandong First Medical University, Taian, 271000, Shandong, China.
  • 5 Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang, 261053, Shandong, China.
  • 6 College of Pharmacy, Weifang Medical University, Weifang, 261053, Shandong, China. dejunding@wfmc.edu.cn.
  • 7 Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang, 261053, Shandong, China. dejunding@wfmc.edu.cn.
  • 8 Department of Pathology, Weifang Medical University, Weifang, 261053, Shandong, China. liwentong11@163.com.
  • 9 Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang, 261053, Shandong, China. liwentong11@163.com.
  • # Contributed equally.
PMID: 35725558 DOI: 10.1038/s41419-022-05007-0
Abstract

Cancer stem cell (CSC) cluster of triple-negative breast Cancer (TNBC) is suggested to be responsible for therapy resistance, metastatic process and Cancer recurrence, yet the sensitivity of CSC clusters of TNBC to Ferroptosis remains elusive in a great measure. Current research revealed that epidermal growth factor receptor (EGFR) reinforced CD44-mediated TNBC cell clustering, whether blockade of EGFR has synergistic effects on erastin-induced tumor inhibition of CSC clusters is still poorly understood. Here, we found that fraction of CD24lowCD44high cells and size of tumor spheres clearly decreased following EGFR inhibition in TNBC cells. Inhibition of EGFR promoted expression of LC3B-II via YAP/mTOR signaling pathway, indicating that EGFR-mediated Autophagy which contributed to Ferroptosis. In order to further verify the protective effects of EGFR on Ferroptosis induced by small molecules in TNBC cells, pseudolaric acid B (PAB) which led to Ferroptosis of malignant cells was selected. In our experiment, lapatinib and PAB cotreatment inhibited TNBC cells viability and restrained formation of tumor spheres, accompanied with a high level of intracellular ROS. To target delivery lapatinib and PAB to TNBC cells, lapatinib/PAB@Ferritin (L/P@Ferritin) nanoparticles were prepared; results of in vitro and in vivo showed a higher tumor suppression efficiency of L/P@Ferritin, highlighting that it might provide a new perspective for treatment of CSC clusters of TNBC.

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