A Combinational Approach Towards Treatment of Breast Cancer: an Analysis of Noscapine-Loaded Polymeric Nanoparticles and Doxorubicin

Our aim in this study was to clarify the combination anticancer effect of Noscapine (Nos) loaded in a polymeric nanocarrier with Doxorubicin (Dox) on breast cancer cells. Nanoprecipitation method was used to prepare methoxy polyethylene glycol (mPEG), poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) containing Nos. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to characterize the prepared Nos NPs. The anticancer activity of Nos NPs alone and in combination with Dox was assessed on 4T1 breast cancer cell line and in mice model. Spherical-shaped Nos NPs were prepared, with size of 101 ± 4.80 nm and zeta potential of - 15.40 ± 1 mV. Fourier transform infrared (FTIR) spectroscopy results demonstrated that Nos chemical structure was kept stable during preparation process. However, differential scanning calorimetric (DSC) thermogram proved that crystalline state of Nos changed to amorphous state in Nos NPs. The entrapment efficacy % (EE%) and drug loading % (DL%) of Nos NPs were about 87.20 ± 3.50% and 12.50 ± 2.30%, respectively. Synergistic anticancer effects of Nos both in free form (in hydrochloride form, Nos HCl) and Nos NPs form with Dox hydrochloride (Dox HCl) were observed on 4T1 cells. Combination of Nos NPs and Dox HCl inhibited tumor growth (68.50%) in mice more efficiently than Nos NPs (55.10%) and Dox HCl (32%) alone. Immunohistochemical (IHC) analysis of the tumor tissues confirmed antiangiogenic effect of Nos NPs. The findings highlighted efficacy of Nos NPs alone and in combination with Dox HCl on breast cancer tumors.

Keywords: breast cancer; combination therapy; doxorubicin; noscapine; polymeric nanoparticles; synergism.