Abstract
Herein, a method for synthesizing and utilizing DNA dendrons to deliver biomolecules to living cells is reported. Inspired by high-density nucleic acid nanostructures, such as spherical nucleic acids, we hypothesized that small clusters of nucleic acids, in the form of DNA dendrons, could be conjugated to biomolecules and facilitate their cellular uptake. We show that DNA dendrons are internalized by 90% of dendritic cells after just 1 h of treatment, with a >20-fold increase in DNA delivery per cell compared with their linear counterparts. This effect is due to the interaction of the DNA dendrons with scavenger receptor-A on cell surfaces, which results in their rapid endocytosis. Moreover, when conjugated to peptides at a single attachment site, dendrons enhance the cellular delivery and activity of both the model ovalbumin 1 peptide and the therapeutically relevant thymosin alpha 1 peptide. These findings show that high-density, multivalent DNA ligands play a significant role in dictating cellular uptake of biomolecules and consequently will expand the scope of deliverable biomolecules to cells. Indeed, DNA dendrons are poised to become agents for the cellular delivery of many molecular and nanoscale materials.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 13513-13518 |
| Number of pages | 6 |
| Journal | Journal of the American Chemical Society |
| Volume | 143 |
| Issue number | 34 |
| DOIs | |
| State | Published - Sep 1 2021 |
Funding
This material is based upon work supported by the Air Force Office of Scientific Research (Award FA9550-17-1-0348) and the Air Force Research Laboratory (Award FA8650-15-2-5518). The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon. M.H.T. gratefully acknowledges support from Cancer Nanotechnology Training Grant T32CA186897. K.E.B. gratefully acknowledges support from a Banting Fellowship from the Government of Canada. M.E. was partially supported by the Dr. John N. Nicholson Fellowship. This work made use of the IMSERC MS facility at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), the State of Illinois, and the International Institute for Nanotechnology (IIN). Peptide Synthesis was performed at the Peptide Synthesis Core Facility of the Simpson Querrey Institute at Northwestern University, with special thanks to Dr. Mark Karver, which has current support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633). Some figures were created with BioRender.
ASJC Scopus subject areas
- General Chemistry
- Biochemistry
- Catalysis
- Colloid and Surface Chemistry