Synthesis of an ethyleneimine/tetrahedral DNA nanostructure complex and its potential application as a multi-functional delivery vehicle.

Nowadays, DNA nanostructures are extensively researched for their biocompatibility, editable functionality, and structural stability. Tetrahedral DNA nanostructures (TDNs), widely known for their membrane permeability, are regarded as potential candidates for drug delivery. However, the stability and membrane permeability of TDNs call for further enhancement if in vivo usage is ascribed. To overcome the drawbacks of TDNs, ethylene imine (PEI, 25 kDa, branched)-a classic cationic polymer in the field of gene delivery-was applied. Via a facile one-pot synthesis method, a PEI/TDNs complex was formed. Subsequently, a DNase protection assay, a cytotoxicity assay, endocytosis-related experiments, and lysosome staining were performed to examine the potential of PEI/TDNs as a delivery vehicle. The combination of PEI and TDNs not only overcame the drawbacks of each substance but also retained their individual merits. Traditionally, drug-delivery vehicles that enable enhanced cell entry and lysosome escape are often compromised by their toxicity and poor multifunctionality. We believe this novel PEI/TDNs complex with enhanced systemic stability, biocompatibility, cell-entry ability, and lysosome-escape ability and unsurpassed editable functionality could be a powerful tool as a multi-functional delivery vehicle in targeted drug delivery, in vivo imaging, and other related fields.