DNA Sequence-Programmed Protein Coronas Determine Intracellular Fate and Proteostatic Stress of Carbon Nanotubes

Single-walled carbon nanotubes (SWCNTs) have potential applications in biosensing, imaging, and drug delivery. However, their safety and efficacy depend on the identity of their biomolecular corona, which forms upon contact with biological fluids. Researchers have now discovered that the sequence of single-stranded DNA wrapping around (6,5)-enriched SWCNTs influences their protein corona, intracellular trafficking, and macrophage response.

By examining (AT)15, (GT)15, and (CT)15 wrapped SWCNTs, the study found that wrapping sequence determines both the protein corona and proteostatic stress on macrophages. Photoluminescence imaging and confocal Raman measurements showed that (AT)15 is internalized most but leaves the proteome and SWCNT structure largely intact, while (CT)15, taken up the least, undergoes the most aggressive degradation and generates the highest oxidative and proteostatic stress.

The study also revealed that all three SWCNTs form coronas with distinct functional identities, leading to different intracellular routes. Time-resolved intracellular proteomics and functional assays demonstrated how the host cell reorganizes its biomolecular complexity over time, including oxidative outputs, along with particle engagement, phagosomal sorting, and lysosomal processing.

This research provides a deeper understanding of nanomaterial-cell interactions and offers a nucleotide-level design handle for controlling the intracellular fate of carbon nanomaterials, which could have implications for safe and effective nanomedicine platforms.