Potent anti-tumor immunostimulatory biocompatible nanohydrogel made from DNA

Abstract

Unmethylated CpG oligodeoxynucleotides are potent immunostimulatory motifs in activating both innate and acquired immune system by inducing Th1 type antigen-specific T cell responses, but their instability in serum greatly influences their immunostimulant efficiency. Here, we constructed a novel immuno-DNA nanohydrogels consisting of tandem repeat sequences of CpG units named CpG-MCA nanohydrogels through multi-primed chain amplification. CpG-MCA nanohydrogels were proved to resist degradation and increase the proliferation and migration of murine macrophage-like RAW264.7 cells. Furthermore, CpG-MCA nanohydrogels effectively induced high expression of tumor necrosis factor-α and interleukin-6, and remarkably inhibited the proliferation of U251 cells, suggesting that CpG-MCA nanohydrogels are expected to be employed as the potent anti-cancer immunostimulant. Electronic supplementary material The online version of this article (10.1186/s11671-019-3032-9) contains supplementary material, which is available to authorized users.

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“…The most commonly applied approaches to enhance the stability of oligo-CpG in physiological conditions is the chemical modification of DNA backbones. The transportation of CpG or CpG modified oligo-CpG into cells via nonspecific endocytosis, limited the immunotherapy [ 189 ]. Rattanakiat et al developed the ligating CpG comprising Y-shaped monomers, dendrimers like DNA [ 190 ].…”

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