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Published on: December 23, 2016
Cross-Linked Micellar Spherical Nucleic Acids from Thermoresponsive Templates
Resham J Banga1, Brian Meckes1, Suguna P Narayan1
1International Institute of Nanotechnology, ‡Department of Chemical and Biological Engineering, §Department of Chemistry, and ∥Department of Biomedical Engineering, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
Abstract:
A one-pot synthesis of micellar spherical nucleic acid (SNA) nanostructures using Pluronic F127 as a thermoresponsive template is reported. These novel constructs are synthesized in a chemically straightforward process that involves intercalation of the lipid tails of DNA amphiphiles (CpG motifs for TLR-9 stimulation) into the hydrophobic regions of Pluronic F127 micelles, followed by chemical cross-linking and subsequent removal of non-cross-linked structures. The dense nucleic acid shell of the resulting cross-linked micellar SNA enhances their stability in physiological media and facilitates their rapid cellular internalization, making them effective TLR-9 immunomodulatory agents. These constructs underscore the potential of SNAs in regulating immune response and address the relative lack of stability of noncovalent constructs.
