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Nanomedicine. 2019 Mar 1. pii: S1549-9634(19)30038-3. doi: 10.1016/j.nano.2019.02.007. [Epub ahead of print]

Cationic lipoplexes for treatment of cancer stem cell-derived murine lung tumors.

Author information

1
Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, Worcester, MA.
2
Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
3
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL. Electronic address: mandip.sachdeva@famu.edu.

Abstract

Side population (SP) cells with stem-like properties, also known as cancer stem cells (CSC) have been recognized as drivers of the resistance phenotype in many cancers. Central to the characteristic stem-like phenotype of CSCs in cancer is the activity of the SOX2 transcription factor whose upregulation has been associated with enrichment of many oncogenes. This study outlines the fabrication of a lipoplex of SOX2 small interfering RNA (CL-siSOX2) for targeted treatment of SOX2-enriched, CSC-derived orthotopic and xenograft lung tumors in CB-17 SCID mice. CL-siSOX2 induced tumor contraction in Cisplatin-naïve and Cisplatin-treated groups by 85% and 94% respectively. Reduction in tumor weight and volume following treatment with CL-siSOX2 was associated with reduced protein expression of SOX2 and markers of tumor initiation, inflammation, invasion and metastasis in mice tumor xenografts. And histological staining of lung tumor sections showed reduction in SOX2 expression was associated with inhibition markers of epithelial-to-mesenchymal transition.

KEYWORDS:

Cancer stem cells; Cationic lipoplex; Gene delivery; Lung cancer; Nanoparticles; SOX2 siRNA

PMID:
30831275
DOI:
10.1016/j.nano.2019.02.007

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