posted on 2020-04-01, 17:34authored byWenqian Yu, Junlin Sun, Feng Liu, Shuyi Yu, Zhen Xu, Fuan Wang, Xiaoqing Liu
Unmethylated
cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides are immunostimulatory
nucleic acids wildly utilized as adjuvants or for vaccines to treat
diseases. However, there is a lack of simple and efficient vectors
for CpG oligodeoxynucleotide delivery with long-lasting immune stimulation.
Herein, self-assembled polymer wires consisting of CpG motifs by hybridization
chain reaction were constructed with excellent biocompatibility and
immunostimulatory activity. The designed polymer DNA wires acted as
programmable multivalent immunoadjuvants and triggered immune response,
stimulated pro-inflammatory cytokine secretion, and induced the apoptosis
of cancer cells. More strikingly, polymer nanospheres assembled from
the polymer DNA wires and cationic poly-l-lysine further
improved cellular uptake and continuously stimulate the lysosomal
Toll-like receptor 9 of immune cells, thereby remarkably enhancing
the activation of immune cells. These results demonstrated that self-assembled
polymer DNA nanoassemblies with multivalent CpG could trigger strong
immune response and further induce cancer cell death.