Tetrahedral DNA nanostructures synergize with MnO_(2) to enhance antitumor immunity via promoting STING activation and M1 polarization

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 Mn^(2+) 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 Mn^(2+),we constructed a TDN-MnO_(2) complex and found that it displayed a much higher efficacy than TDN plus Mn^(2+) 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 MnO_(2).These findings provide new therapeutic opportunities for cancer therapy.

Effect of tetrahedral DNA nanostructures on LPS-induced neuroinflammation in mice

Neuroinflammation plays a significant role in inducing depression-like behavior. Tetrahedral DNA nanostructures(TDNs) are molecules that exhibit anti-inflammatory properties and can effectively penetrate the blood-brain barrier. Thus, researchers have hypothesized that TDNs regulate the secretion of proinflammatory cytokines and consequently alleviate depression-like behavior. To test this hypothesis, we investigated the effect of TDNs on the depression-like behavior of C57 mice induced by lipopolysaccharide(LPS). We performed open-field, tail suspension, and sucrose preference tests on LPS-and LPS/TDNtreated mice. The results indicated that the injection of TDNs into LPS-treated mice resulted in increased velocity, center zone duration, frequency to the center zone, and sucrose preference, and decreased immobility time. Immunofluorescence results indicated that peripheral administration of LPS in the mice activated inflammation, which culminated in distinct depression-like behavior. However, TDNs effectively alleviated the inflammation and depression-like behavior through the reduction of the expression levels of proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α in the brain. Additionally, TDNs normalized the expression level of microglia cell activation markers, such as ionized calcium binding adaptor molecule 1, in the hippocampus of mice. These results indicated that TDNs attenuated the LPS-induced secretion of inflammatory factors and consequently alleviated depression-like behavior.

Applications of tetrahedral DNA nanostructures in wound repair and tissue regeneration

Tetrahedral DNA nanostructures(TDNs)are molecules with a pyramidal structure formed by folding four single strands of DNA based on the principle of base pairing.Although DNA has polyanionic properties,the special spatial structure of TDNs allows them to penetrate the cell membrane without the aid of transfection agents in a caveolin-dependent manner and enables them to participate in the regulation of cellular processes without obvious toxic side effects.Because of their stable spatial structure,TDNs resist the limitations imposed by nuclease activity and innate immune responses to DNA.In addition,TDNs have good editability and biocompatibility,giving them great advantages for biomedical applications.Previous studies have found that TDNs have a variety of biological properties,including promoting cell migration,proliferation and differentiation,as well as having anti-inflammatory,antioxidant,anti-infective and immune regulation capabilities.Moreover,we confirmed that TDNs can promote the regeneration and repair of skin,blood vessels,muscles and bone tissues.Based on these findings,we believe that TDNs have broad prospects for application in wound repair and regeneration.This article reviews recent progress in TDN research and its applications.

Superresolution imaging of DNA tetrahedral nanostructures in cells by STED method with continuous wave lasers

DNA tetrahedral nanostructures are considered to be uew nanocarriers because they can be precisely controlled and hold excellent penetration ability to the cellular membrane. Although the DNA tetrahedral nanostructure is extensively studied in biology and medicine, its behavior in the cells with nanoscale resolution is not understood clearly. In this letter, we demonstrate superrcsolution fluorescence imaging of the distribution of DNA tetrahedral nanostructures in the cell with a simulated emission depletion （STED） microscope, which is built based on a conventional eonfocal microscope and can t）rovide a resolution of 70 nm.

Coating with flexible DNA network enhanced T-cell activation and tumor killing for adoptive cell therapy

Adoptive cell therapy(ACT)is an emerging powerful cancer immunotherapy,which includes a complex process of genetic modification,stimulation and expansion.During these in vitro or ex vivo manipulation,sensitive cells are inescapability subjected to harmful external stimuli.Although a variety of cytoprotection strategies have been developed,their application on ACT remains challenging.Herein,a DNA network is constructed on cell surface by rolling circle amplification(RCA),and T cell-targeted trivalent tetrahedral DNA nanostructure is used as a rigid scaffold to achieve high-efficient and selective coating for T cells.The cytoprotective DNA network on T-cell surface makes them aggregate over time to form cell clusters,which exhibit more resistance to external stimuli and enhanced activities in human peripheral blood mononuclear cells and liver cancer organoid killing model.Overall,this work provides a novel strategy for in vitro T cell-selective protection,which has a great potential for application in ACT.