All-in-one Biocomputing Nanoagents with Multilayered Transformable Architecture based on DNA Interfaces

The pathogen diversity to infiltrate the host organism highlights the demand for equally sophisticated mechanisms for their prevention. The development of "intelligent" agents with molecular logic capabilities are of great hope, but their full theranostic potential has yet to be realized. Methods: The original concept of nanoagents based on "Biocomputing based on particle disassembly" technology has been extended to nucleic acids (NAs) interfaces and inputs. By exploiting the unique properties of NAs, we designed nanostructures that can implement all basic single- and dual-input logic gates on a unified nanoparticle platform through DNA strand displacement triggered by oligonucleotide inputs. Performance of nanostructures was investigated across various output signal detection formats including specific interaction with nanosized objects and targeting cells. Results: Here, we demonstrate autonomous theranostic biocomputing agents based on nanoparticles and DNA interfaces ("DNA-transformers") capable of executing a functionally complete set of Boolean logic gates (YES, NOT, AND, and OR) within a single all-in-one particle structure. Each DNA-transformer is constructed through a multi-layered self-assembly of nanoparticles via DNA-interfaces. The route of the agent's disassembly induced by the particular combination of the specific ssDNA inputs determines the agents' ability to produce the programmed outputs compatible with theranostic applications such as specific targeting of HER2/neu-positive cancer cells. Conclusions: The developed all-in-one DNA-based nanoagents represent a significant advancement in molecular logic devices, establishing a versatile platform for smart nanoagents equally suitable for diagnostic and therapeutic applications.