•  
  •  
 
Nano Research

Article Title

NVP-BEZ235/Chlorin-e6 co-loaded nanoparticles ablate breast cancer by biochemical and photodynamic synergistic effects

Authors

Ahmed Shaker Eltahan, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China University of Chinese Academy of Sciences, Beijing 100049, China
Lu Liu, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China University of Chinese Academy of Sciences, Beijing 100049, China Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome 00133, Italy
Chukwunweike Ikechukwu Okeke, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China University of Chinese Academy of Sciences, Beijing 100049, China
Min Huang, Beijing Engineering Research Center of Printed Electronics, Beijing Institute of Graphic Communication, Beijing 102600, China
Lu Han, Beijing Engineering Research Center of Printed Electronics, Beijing Institute of Graphic Communication, Beijing 102600, China
Jing Chen, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China
Xue Xue, State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300350, China
Massimo Bottini, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome 00133, Italy
Weisheng Guo, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China
Xing-Jie Liang, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China University of Chinese Academy of Sciences, Beijing 100049, China

Keywords

nanomedicine, triple-negative breast cancer, NVP-BEZ235, photodynamic therapy, synergistic therapy

Abstract

ABSTRACT Seeking profitable therapies for triple-negative breast cancer (TNBC) has attracted intense research interest. However, an efficient cure for TNBC remains an unresolved challenge in oncology. Herein, for the first time, we describe the use of polymeric nanoparticles loaded with NVP-BEZ235 and Chlorin-e6, denoted as NVP/Ce6@NPs, to overcome the adaptive treatment tolerance of TNBC by taking advantage of the synergistic effect between biochemical and photodynamic therapies. Upon laser irradiation, the NVP/Ce6@NPs generated reactive oxygen species (ROS) and efficiently induced the apoptosis of tumor cells through DNA damage. Furthermore, the released NVP-BEZ235 could prevent Chk1 phosphorylation-induced DNA damage repair, thus enhancing the sensitivity of tumor cells to ROS. Animal studies on mice bearing an MDA- MB-231 tumor validated that the NVP/Ce6@NPs had a greater therapeutic efficacy compared to that of monotherapies, with an inhibition ratio of 89.3%. Western blotting and cell viability analyses confirmed the inhibition of both MDA-MB-231 cell proliferation and Chk1 phosphorylation by NVP/Ce6@NPs. These findings provide a rational understanding of the synergistic effect of the biochemical/photodynamic therapy and pave the way for the development of efficient therapeutic approaches to fight against TNBC.

Graphical Abstract

Publisher

Tsinghua University Press

Share

COinS