Well-Defined DNA-Polymer Miktoarm Stars for Enzyme-Resistant Nanoflares and Carrier-Free Gene Regulation.

Herein, we report a star-architectured poly(ethylene glycol) (PEG)-oligonucleotide nanoconjugate of a well-defined molecular structure. Based upon fullerene C60 cores, each star bears precisely 1 DNA strand and 11 polymer chains. The elevated PEG density provides the DNA with steric selectivity: the DNA is significantly more resistant to nuclease digestion while remaining able to hybridize with a complementary sequence. The degree of resistance increases as the centers of mass for the DNA and fullerene are closer together. Such steric selectivity reduces protein-related background signals of the nanoflares synthesized from these miktoarm star polymers. Importantly, the stars improve cellular uptake and regulate gene expression as a non-cytotoxic, single-entity antisense agent without the need for a transfection carrier.