In summary, we found TRPC6, TRPM7, TRPM8, SLC41A1, SLC41A2, ORAI1, ORAI3, and ATP2C1 to be promising therapeutic targets for siRNA-mediated knockdown in breast cancer cells, with the simultaneous knockdown of TRPC6, TRPM8, SLC41A2, and MAGT1 through the CA NP-assisted combined delivery of respective siRNAs, resulting in a synergistic effect on cytotoxicity. Here, ORAI1 is linked to breast carcinoma.