International Journal of Nanomedicine (Nov 2020)

89Zr-Labeled Multifunctional Liposomes Conjugate Chitosan for PET-Trackable Triple-Negative Breast Cancer Stem Cell Targeted Therapy

  • Yang R,
  • Lu M,
  • Ming L,
  • Chen Y,
  • Cheng K,
  • Zhou J,
  • Jiang S,
  • Lin Z,
  • Chen D

Journal volume & issue
Vol. Volume 15
pp. 9061 – 9074

Abstract

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Rui Yang,1,* Mudan Lu,2,* Lan Ming,1,* Yu Chen,1 Kai Cheng,1 Jie Zhou,1 Shiwen Jiang,1 Zhenyu Lin,3 Daozhen Chen1 1Research Institute for Reproductive Health and Genetic Diseases, Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi 214002, People’s Republic of China; 2Internal Medicine, Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi 214002, People’s Republic of China; 3Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection for Food Safety, College of Chemistry, Fuzhou University, Fuzhou 350116, People’s Republic of China*These authors contributed equally to this workCorrespondence: Daozhen ChenResearch Institute for Reproductive Health and Genetic Diseases, Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi 214002, People’s Republic of ChinaTel +86-13584189188Fax +86-510-82725094Email [email protected]: Therapy for triple-negative breast cancer (TNBC) is a global problem due to lack of specific targets for treatment selection. Cancer stem cells (CSCs) are responsible for tumor formation and recurrence but also offer a promising target for TNBC-targeted therapy. Here, zirconium-89 (89Zr)-labelled multifunctional liposomes (MLPs) surface-decorated with chitosan (CS) were fabricated to specifically target and trace cluster of differentiation 44+ (CD44+) TNBC CSCs specifically.Patients and Methods: The biological basis of CS targeting CD44 for cancer therapy was investigated by detecting the expression of CD44 in TNBC CSCs and TNBC tissues. Molecular docking and dynamics simulations were performed to investigate the molecular basis of CS targeting CD44 for cancer therapy. Gambogic acid (GA)-loaded, 89Zr@CS-MLPs (89Zr-CS-GA-MLPs) were prepared, and their uptake and biodistribution were observed. The anti-tumor efficacy of 89Zr@CS-GA-MLPs was investigated in vivo.Results: CD44 is overexpressed in TNBC CSCs and tissues. Molecular docking and dynamics simulations showed that CS could be stably docked into the active site of CD44 in a reasonable conformation. Furthermore, 89Zr@CS-GA-MLPs were able to bind specifically to CD44+ TNBC stem-like cells and accumulated in tumors of xenograft-bearing mice with excellent radiochemical stability. 89Zr@CS-GA-MLPs loaded with GA showed remarkable anti-tumor efficacy in vivo.Conclusion: The GA-loaded, 89Zr-labelled, CS-decorated MLPs developed in this study represent a novel strategy for TNBC imaging and therapy.Keywords: radionuclide, PET, CS, CD44, molecular docking, molecular dynamics simulation

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