Abstract
The single-stranded DNA oligonucleotides known as aptamers have the capacity to bind proteins and other molecules and offer great therapeutic potential. Further work is required to optimize their function and to diminish their susceptibility to nuclease degradation. We report here on the synthesis and supramolecular self-assembly of DNA-peptide amphiphiles that form high aspect ratio nanofibers and display aptamers for the platelet-derived growth factor. The nanofibers were found to bind the growth factor with an affinity that was 5-fold greater than the free aptamer. We also observed that the aptamer displayed by the supramolecular nanostructures was eight times more nuclease-resistant than the free aptamer. In order to highlight the therapeutic potential of these supramolecular systems, we demonstrated the improved inhibition of proliferation when the growth factor was bound to aptamers displayed by the nanofibers.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2955-2963 |
| Number of pages | 9 |
| Journal | ACS Applied Bio Materials |
| Volume | 2 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jun 18 2019 |
Funding
This project was supported by the National Institutes of Health NIDCR (grant no. 2R01DE015920-11) and the Northwestern University Center for Regenerative Nanomedicine (CRN) through a Catalyst Award. C.M.S. acknowledges support from the NSF Graduate Research Fellowship Program. R.F. acknowledges support from an EMBO Long-Term Postdoctoral Fellowship (ALTF 233-2012). J.G. acknowledges support from Northwestern University through a Ryan Fellowship. J.A.L. acknowledges support from a National Science Foundation Graduate Research Fellowship. We are grateful to the Peptide Synthesis Core and the Analytical bioNanoTechnology Core at the Simpson Querrey Institute at Northwestern University. The U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command, and Northwestern University provided funding to develop these facilities and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205). The authors acknowledge also the use of the following Northwestern University facilities: The Biological Imaging Facility (supported by the Northwestern University Office for Research), the Keck Biophysics Facility (supported by the NCI CCSG P30 CA060553. This project was supported by the National Institutes of Health NIDCR (grant no. 2R01DE015920-11) and the Northwestern University Center for Regenerative Nanomedicine (CRN) through a Catalyst Award. C.M.S. acknowledges support from the NSF Graduate Research Fellowship Program. R.F. acknowledges support from an EMBO Long-Term Postdoctoral Fellowship (ALTF 233-2012). J.G. acknowledges support from Northwestern University through a Ryan Fellowship. J.A.L. acknowledges support from a National Science Foundation Graduate Research Fellowship. We are grateful to the Peptide Synthesis Core and the Analytical bioNanoTechnology Core at the Simpson Querrey Institute at Northwestern University. The U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command, and Northwestern University provided funding to develop these facilities and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205). The authors acknowledge also the use of the following Northwestern University facilities: the Biological Imaging Facility (supported by the Northwestern University Office for Research), the Keck Biophysics Facility (supported by the NCI CCSG P30 CA060553 grant awarded to the Robert H. Lurie Comprehensive Cancer Center), and the Electron Probe Instrumentation Center facility of Northwestern University’s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205). This work made use of the IMSERC at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205), the State of Illinois, and the International Institute for Nanotechnology (IIN). This research used resources of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. This work also made use of the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the APS. DND-CAT is supported by Northwestern University, E.I. DuPont de Nemours & Co., and The Dow Chemical Company. The authors also thank Mark Seniw for designing the schematic drawing in the manuscript.
Keywords
- aptamer
- biomaterials
- hybrid
- nanotechnology
- peptide amphiphile
- self-assembly
ASJC Scopus subject areas
- Biomaterials
- General Chemistry
- Biomedical Engineering
- Biochemistry, medical