Nanotechnology approach for targeted treatment of triple negative breast cancer

Breast cancer is one of the most devastating diseases worldwide. Triple negative breast cancer cells (TNBCs) are defined by the lack of progesterone receptor (PR), estrogen receptor (ER), and epidermal growth factor receptor 2 (EGFR2) expressions. TNBCs account for 10%- 20% of all breast carcinomas. The study is aimed at examining the efficacy of gefitinib and EGFR-targeted siRNA delivered by liposomes for treating triple negative breast cancer (TNBC). The experiments were carried out using two types of human breast cancer (BC) cell lines MCF-7 (estrogen positive BC, EPBC) and MDA-MB 231(TNBC). EGFR-targeted siRNA and gefitinib were delivered by cationic and neutral liposomes, respectively. A fluorescence microscope was used to study cellular internalization of labeled liposomes and siRNA. The expression of the targeted mRNA was performed using quantitative reverse transcription PCR. Finally, cytotoxicity of liposomal siRNA and gefitinib alone or in combination was measured using the modified MTT assay with appropriate controls. It was found that liposomes effectively delivered siRNA into both types of BC cells and suppressed the expression of targeted EGFR mRNA. However, formulations without gefitinib did not influence significantly on the viability of BC cells. Free drug demonstrated the ability to kill both types of cancer cells. Nevertheless, toxicity of gefitinib in TNBC was 2.5 times lower when compared with EPBC cells. The delivery of the drug by liposomes significantly enhanced its toxicity (1.2 and 2.5 times in EPBC and TNBC, respectively). The combination of liposomal siRNA and liposomal gefitinib demonstrated exceptionally high cytotoxicity when compared with the free drug (143 and 62 times higher in EPBC and TNBC, respectively). Suppression of EGFR mRNA effectively suppressed resistance of TNBC cells to gefitinib. The data obtained support the proposed approach and showed high potential of liposomal EGFR siRNA in combination with liposomal gefitinib in treatment of TNBC.M.S.Includes bibliographical referencesby Sumayah Abed Ahmed Al-Mahmoo