The niosomal nelarabine as a promising nano combination for retinoblastoma treatment: an in vitro study-experimental research.

Abstract

Introduction: Retinoblastoma (RB), the most commonly occurring intraocular malignancy among children globally, represents 3% of childhood cancers. In the current study, the authors aim to evaluate the effectiveness of a new formulation of nelarabine (niosomal nelarabine) on RB cancer cells.

Methods: Field emission scanning electron microscopy (FE-SEM) and dynamic light scattering (DLS) characterized the physical properties of nelarabine nanoparticles. After cultivation of the Y79 cell line, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was performed to determine IC50 of niosomal nelarabine (Nio-Nelarobine) and also the cytotoxicity of Nio-Nelarobine and doxorubicin against Y79 cell line was investigated. The level of apoptosis was assessed by flow cytometry in selected groups. Also, the PTEN/AKT/FOXO1 gene expression level was measured using qRT-PCR.

Results: Y79 cell lines were treated with Nio-Nelarobine and doxorubicin. The treatment resulted in a dose-dependent inhibition of Y79 cell viability. However, Nio-Nelarobine showed a higher inhibitory activity with a diameter of about 167 nm. Both Nio-Nelarobine and doxorubicin induced apoptosis in cells, but Nio-Nelarobine treatment resulted in a higher number of apoptotic cells than doxorubicin treatment. The qRT-PCR results showed that the treatment with Nio-Nelarobine and doxorubicin led to an increase in the expression of PTEN and FOXO1 genes, while decreasing the expression of the AKT gene. Furthermore, the statistical significance of these results was higher in the Nio-Nelarobine group than in the doxorubicin group.

Conclusions: Nio-Nelarobine may be a functional therapeutic combination for RB treatment. Further experimental and preclinical investigations are necessary to verify this impact in greater detail.