RESUMO
Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn2+ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn2+, we constructed a TDN-MnO2 complex and found that it displayed a much higher efficacy than TDN plus Mn2+ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO2. These findings provide new therapeutic opportunities for cancer therapy.
RESUMO
DNA is a biological polymer that encodes and stores genetic information in all living organism. Particularly, the precise nucleobase pairing inside DNA is exploited for the self-assembling of nanostructures with defined size, shape and functionality. These DNA nanostructures are known as framework nucleic acids (FNAs) for their skeleton-like features. Recently, FNAs have been explored in various fields ranging from physics, chemistry to biology. In this review, we mainly focus on the recent progress of FNAs in a pharmaceutical perspective. We summarize the advantages and applications of FNAs for drug discovery, drug delivery and drug analysis. We further discuss the drawbacks of FNAs and provide an outlook on the pharmaceutical research direction of FNAs in the future.