Structural DNA nanotechnology-guided spatially-ordered arrangement of aptamers on natural killer cells for solid tumor immunotherapy.

While natural killer (NK) cells are able to kill malignant cells, NK-base immunotherapies of solid tumors remain limited due to lack of specific targeting. In this work, NK-92MI cells were artificially-engineered with two aptamers designed to specifically bind cancer cells. The strategy used a mild reduction strategy to install aptamer-associated Y-shaped backbone-rigidified three-dimensional DNA tetrahedrons (RDTs) on NK cells. The resulting d-RDT-NK cells exhibited a enhanced tumor-targeting ability in vitro. After systemic administration into a HeLa tumor-bearing BALB/c nude mouse model, the engineered cells accumulated in tumor tissues and exhibited enhanced tumor inhibition activity and lack of detectable systemic toxicity. This method offers insights into the potential application of backbone-mediated structural DNA nanotechnology in artificially engineering of immune effector cells for improved targeting, hopefully opening new avenues for the clinical applications of NK cell immunotherapy in solid tumors.