Abstract: Background and Objective: Alendronate sodium (ALS) is a member of the class bisphosphonates used to treat osteoporosis. Recent reports suggested that ALS may induce cell death and inhibit the proliferation of estrogen-sensitive MCF-7 breast cancer cells. The aim of this work was the combination of ALS and trans-activating regulatory protein (TAT) loaded nanostructured lipid carriers (NLCs) to potentiate ALS cytotoxicity against MCF-7 breast cancer cells. Materials and Methods: The ALS and TAT were prepared and loaded in NLCs. The formed NLCs were characterized for entrapment efficiency (%) (EE %), particle size and zeta potential. Cell viability was also carried out for the prepared NLCs. Results: The results revealed that the prepared NLCs were spherical, with particle sizes of 285.2±14.1 nm and polydispersity index of 0.51. Zeta potential of ALS-TAT-NLCs was +21.1±3.4 mV. The ALS EE percentage of the prepared NLCs was 12.2±1.1%. At concentration of 10 μg mL–1, the investigated formulations showed cell survival percentage of 6.86, 20.34, 97.53 and 91.55% for ALS-TAT NLCs, raw ALS, raw TAT and plain NLCs, respectively. The IC50 values for the treatments were estimated as follows: ALS-TAT NLCs, 1.98±0.17 μg mL–1, raw ALS, 2.77±0.36 μg mL–1, raw TAT, 1066.67±21.22 μg mL–1 and plain NLCs, 10816.2±112.32 μg mL–1. Conclusion: The combination of ALS with TAT protein loaded NLCs offered a dual mechanism of ALS activity potentiation and a promising candidate for breast cancer therapy.