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89Zr-Labeled Multifunctional Liposomes Conjugate Chitosan for PET-Trackable Triple-Negative Breast Cancer Stem Cell
Rui Yang1, Mudan Lu2, Lan Ming1
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.
Purpose:
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.
Insights
This study developed novel zirconium-89 labeled chitosan-decorated liposomes to target triple-negative breast cancer stem cells. These liposomes show promise for both imaging and treating TNBC by targeting CD44+ cancer stem cells.
Area of Science:
- Nanotechnology
- Biomedical Engineering
- Oncology
Background:
- Triple-negative breast cancer (TNBC) lacks specific treatment targets.
- Cancer stem cells (CSCs) drive TNBC tumor formation and recurrence.
- Targeting CD44+ TNBC CSCs presents a therapeutic opportunity.
Purpose of the Study:
- To develop zirconium-89 (89Zr)-labeled multifunctional liposomes (MLPs) decorated with chitosan (CS).
- To specifically target and trace CD44+ TNBC CSCs for improved imaging and therapy.
- To investigate the anti-tumor efficacy of these novel nanocarriers.
Main Methods:
- Investigated CD44 expression in TNBC CSCs and tissues.
- Performed molecular docking and dynamics simulations for CS-CD44 interaction.
- Prepared and characterized 89Zr-labeled, CS-decorated, gambogic acid (GA)-loaded MLPs (89Zr@CS-GA-MLPs).
- Evaluated in vitro cell uptake and in vivo biodistribution and anti-tumor efficacy.
Main Results:
- CD44 was found to be overexpressed in TNBC CSCs and tissues.
- Simulations confirmed stable docking of CS to the CD44 active site.
- 89Zr@CS-GA-MLPs specifically bound to CD44+ TNBC cells and accumulated in tumors.
- In vivo studies demonstrated remarkable anti-tumor efficacy of 89Zr@CS-GA-MLPs.
Conclusions:
- Chitosan-decorated, 89Zr-labeled MLPs offer a novel strategy for TNBC imaging.
- These nanocarriers provide a promising platform for targeted TNBC therapy.
- The developed system effectively targets CD44+ TNBC CSCs for combined diagnostic and therapeutic applications.
