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Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy
Chiara Brignole1, Veronica Bensa1, Nuno A Fonseca2,3
1Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Summary
Neuroblastoma (NB) cells express cell surface Nucleolin (NCL), a potential therapeutic target. Targeted nanoparticles effectively delivered chemotherapy to NB tumors, showing significant anti-tumor activity in preclinical models.
Area of Science:
- Oncology
- Biochemistry
- Nanomedicine
Background:
- Neuroblastoma (NB) is a common and aggressive pediatric cancer.
- Nucleolin (NCL) is overexpressed on adult tumor cells, but its role in pediatric tumors, especially NB, is largely unknown.
- Cell surface expression of NCL in NB has not been previously reported.
Purpose of the Study:
- To investigate the expression of cell surface Nucleolin (NCL) in neuroblastoma (NB).
- To evaluate the therapeutic potential of NCL-targeting nanoparticles loaded with doxorubicin (DXR) for NB treatment.
Main Methods:
- Cell surface NCL expression was analyzed in NB cell lines, NB tumors, and bone marrow-infiltrating NB cells using Flow Cytometry, Imaging Flow Cytometry, and Immunohistochemistry.
- The efficacy of F3 peptide-decorated doxorubicin-loaded nanocarriers (T-DXR) was assessed in vitro for NB cell proliferation inhibition and cell death induction.
- The in vivo anti-tumor potential of T-DXR was evaluated in metastatic and orthotopic NB animal models.
Main Results:
- Cell surface NCL expression was confirmed in NB cell lines, patient-derived NB tumors, and 70% of bone marrow-infiltrating NB cells.
- NCL staining was observed on both NB tumor cells and tumor endothelial cells in xenografts.
- F3 peptide-targeted nanoparticles selectively internalized into NB cells expressing cell surface NCL.
- T-DXR demonstrated significantly enhanced inhibition of NB cell proliferation and reduced cell viability in vitro compared to untargeted nanoparticles.
- T-DXR treatment led to a significant delay in tumor growth across all tested NB animal models compared to controls and untargeted formulations.
Conclusions:
- Nucleolin (NCL) is expressed on the cell surface of neuroblastoma (NB) cells.
- Cell surface NCL represents a promising and innovative therapeutic target for NB.
- NCL-targeted nanocarrier drug delivery systems show significant therapeutic potential against NB in preclinical settings.
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