There is a lack of research in the literature on the application of nanoparticles to different cascade cycle configurations with environmental refrigerants in ultra-low temperature refrigeration applications. This study is the first on the use of nano-refrigerants in cascade refrigeration cycles. In this study, the effect of 2 wt.% of CuO to RE170 and R170-pure refrigerant utilization in cascade vapor compression refrigeration cycle (CVCRC), cascade ejector refrigeration cycle (CERC) and cascade ejector intercooler refrigeration cycle (CEIRC) are investigated to achieve higher performance values in ultra-low temperature applications. For CVCRC, CERC and CEIRC, the increases in terms of coefficient of performance (COP) with the use of nano-refrigerant were found to be 12.77 %, 8.20 %, and 6.37 %, respectively, and 18.55 %, 14.05 %, and 6.07 %, for exergy efficiency. Upon scrutinizing the results with nano-refrigerant in relation to the COP, the analysis revealed that the CEIRC cycle exhibited an improvement ranging from 13.43 % to 20.49 % in comparison to CERC. Additionally, with nano-refrigerant, the CEIRC cycle demonstrated an increase ranging from 42.39 % to 75.41 % when compared to CVCRC in COP. It was observed that the utilization of CEIRC led to a 13.03 % decrease in kg CO2 emissions in compared to CERC and a reduction of 32.53 % compared to CVCRC with using nano-refrigerant.