Targeted delivery of microRNA-145 to metastatic breast cancer by peptide conjugated branched PEI gene carrier

Abstract

Development of a targeted polymeric gene delivery system is essential for reducing the non-specific uptake and toxicity of the gene carriers. In this study, we have tested the specificity of the cell penetrating peptide (DS 4-3), screened by phage display technique, towards metastatic breast cancer cells. This peptide has shown specificity towards metastatic breast cancer cells, which was confirmed through endocytosis inhibition study. Furthermore, the DS 4-3 peptide was conjugated to bPEI, to deliver the therapeutic miR-145. Tumor suppressor miR-145 inhibited tumor cell growth, and significantly suppressed cell invasion. The DS 4-3 peptide conjugated branched PEI (DSbPEI)/pLuc nanoparticles showed increased transfection in malignant murine breast cancer cells at the neutral surface charge (N/P molar ratio of 3), compared to scramble peptide conjugated bPEI/pLuc nanoparticles, without causing any cytotoxicity. This specific increase in transfection with DS-bPEI/pLuc nanoparticles was not found in the cancer cells that originated from different tissue, such as HeLa cervical cancer cells, or in the normal cells, such as NIH-3T3 murine fibroblast cells. Thus, the specific transfection of miR-145 in metastatic breast cancer cells mediated by DS-bPEI resulted in enhanced reduction in proliferation.