Enhanced Immunostimulatory Activity of a Cytosine-Phosphate-Guanosine Immunomodulator by the Assembly of Polymer DNA Wires and Spheres

Abstract

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.

Visualization of Vaccine Dynamics with Quantum Dots for Immunotherapy

“…Owing to the residence of TLR9 in the lysosome, [34] clathrin‐mediated endocytic pathway of nanovaccines would be beneficial to potentiate the activity of CpG, thereby enhancing the immunoactivation of RAW264.7 cells. The interaction between nanovaccines and lysosome directly affects the efficacy of TLR9 activation [34, 35] . Therefore, the co‐localization of nanovaccines with lysosome and its transfer process into lysosome in RAW264.7 cells was next investigated.…”

Functional Immunostimulating DNA Materials: The Rising Stars for Cancer Immunotherapy

“…Reproduced with permission. [ 55 ] Copyright 2017, Nature Publishing Group. I) CpG motifs buried in DNA nanoflowers.…”

“…assembled micrometer‐long polymer DNA nanowires for the delivery of CpG motifs via enzyme‐free hybridization chain reaction (HCR) method (Figure 2J). [ 55 ] DNA hairpins carrying CpG motifs were used as the HCR monomers and the initiation of an HCR reaction generated DNA nanowires encoding multivalent CpG motifs. They demonstrated that CpG motifs clustered in polymers facilitated their cellular uptake by RAW264.7 cells.…”

Construction of Smart Stimuli‐Responsive DNA Nanostructures for Biomedical Applications

“…Reproduced from ref. [99] with permission from American Chemical Society, copyright 2020. (F) The pH-responsive triplex-based HCR-assembled microcapsules for controllable release of semiconductor payloads.…”

“…Cytosine-phosphate-guanosine (CpG) was encoded into HCR-produced polymeric dsDNA nanowires and spheres with improved immunostimulatory activity ( Figure 4E). [99] The DNA nanowires were constructed by the self-assembly of the CpG-involved HCR hairpin monomers. Then, the dsDNA nanowires were assembled with cationic poly-l-lysine (PLL) to form polymer nanospheres, which could remarkably improvet he cellular uptake with enhanced immune cell activation for effective tumor treatment.…”