In the last decades, natural killer (NK) cells are been considered promising specialized immune cells that can be genetically engineered for improving the cancer treatment for patients who are resistant to conventional therapies. These immune effector cells present an efficient recognition and cytolytic activity against malignant cells. However, the success of NK-based therapies is limited by the availability of safe and effective vectors that ensure entry and proper intracellular disposition of the nucleic acid in the target cell. In this sense, non-viral vectors are easier to produce in large scales and a safer alternative to virus based vectors, but present low transfection efficacy. Solid lipid nanoparticles (SLNs) are a very promising non-viral vectors that have a great capacity to condense nucleic acids and protect them from the nucleases-mediated degradation. SLNs are made of biocompatible and biodegradable materials that facilitate their internalization into target cells. Moreover, they can be functionalized and redirected selectively to specific tissues in order to increase their efficiency, and have an excellent safety profile supported by their use as mRNA delivery systems in vaccines against the SARS-CoV-2. In the present study, we have designed different formulations based on SLN-DNA complexes for transfection of adult peripheral blood NK cells and evaluated internalization efficiency and cell viability. These non-viral delivery systems could be implemented into immunotherapy field generating safer CAR-NK therapies.