Effective drug combinations of betulinic acid and ceranib-2 loaded Zn:MnO2 doped-polymeric nanocarriers against PC-3 prostate cancer cells

Abstract

The development of theranostic nanocarriers with synergistic drug combinations has received considerable attention due to their improved pharmaceutical activity. Herein, we reported an investigation about the in-vitro anticancer activity of ceranib-2 (Cer), betulinic acid (BA), and the combination of betulinic acid and ceranib-2 (BA-Cer) against PC-3 prostate cancer cells. For this purpose, first we designed a suitable nanocarrier using a novel Zn:MnO2 nanocomposite (NCs) and gallic acid (GA)-polylactic acid (PLA)-Alginate polymeric shell with nanoscale particle size and good stability. Chemical statements, morphology, and physicochemical properties of the nanocarrier have been illuminated with advanced characterization techniques. According to the transmission electron microscopy (TEM) results, Zn:MnO2 NCs had a spherical and monodispersed morphology with a 2.03 ± 0.67 nm diameter. Moreover, vibrating-sample magnetometer (VSM) results showed that Zn:MnO2 had paramagnetic properties with a saturation magnetization (Ms) value of 1.136 emu/g. Additionally, the in-vitro cytotoxic effects of the single and binary drugs loaded Zn:MnO2-doped polymeric nanocarriers against PC-3 prostate cancer cells were investigated. According to the results, there was no significant cytotoxic effect of free BA and Cer against PC-3 prostate cancer cells. However, BA/Zn:MnO2@GA-PLA-Alginate NCs, BA-Cer/Zn:MnO2 @GA-PLA-Alginate NCs and free BA-Cer had IC50 values of 6.498, 7.351, and 18.571 μg/mL, respectively. Consequently, BA-Cer/Zn:MnO2@GA-PLA-Alginate is a nanocarrier with good stability, enhanced drug loading and release capacity for hydrophobic drugs, as well as being used as both imaging and treatment agent due to its magnetic properties. Furthermore, BA and Cer drug combination showed great promise in prostate cancer therapy which is known to be resulted high drug resistance. We strongly believed that this work could lead to an investigation of the molecular mechanisms of BA-mediated cancer theapy.