Supramolecular Self‐Assembled DNA Nanosystem for Synergistic Chemical and Gene Regulations on Cancer Cells

Abstract

Incorporating multiple molecular interactions within asystem to realize the metabolic reprogramming of cancer cells is prospected to be of great potential in cancer therapy. Herein, we report asupramolecular self-assembled DNAnanosystem, which reprogrammed the cellular antioxidant system via synergistic chemical and gene regulations.I nt he nanosystem, amphipathic telluroether was coordinated with Mn II to selfassemble into micelle,o nw hich as iNrf2 integrated DNA network was assembled. The great electron-donating capability of telluroether was revealed to greatly promote Mn II -based Fenton-like reaction to generate subversive COH in cancer cells. In response to adenosine triphosphoric acid, the siNrf2 was specially released in cytoplasm for down-regulating expression of detoxification enzymes,w hiche nhanced chemocatalysismediated oxidative stress in cancer cells,t hus significantly suppressing tumor progression.

Framework Nucleic Acids Enabled Pulmonary Artery Endothelial Cell Growth Inhibition by Targeting microRNA‐152

“…Li et al. reported a supramolecular DNA nanometer system that interferes with cellular antioxidant systems [18] . Previously, we demonstrated that framework nucleic acids carrying functional DNA segments (single‐ or double‐stranded DNA) can capture intracellular miRNAs in cancer [19] .…”

“…[17] Li et al reported a supramolecular DNA nanometer system that interferes with cellular antioxidant systems. [18] Previously, we demonstrated that framework nucleic acids carrying functional DNA segments (single-or doublestranded DNA) can capture intracellular miRNAs in cancer. [19] In another study, we showed that self-assembled siRNA-loaded DNA nanoparticles could regulate endothelial cell permeability and apoptosis.…”

Dynamic Transformation of DNA Nanostructures inside Living Cells

“…In 2021, we constructed a supramolecular selfassembled DNA nanosystem, which could enhance the oxidative stress of tumor cells through synergistic chemical and genetic regulation (Figure 4). [23] The synthesized amphiphilic telluride ether was coordinated with Mn 2 + to form a Te/Mn coordination complex (Te/Mn). The cholesterol-modified DNA (I-DNA) anchored on Te/Mn via hydrophobic interaction could initiate cascade clamped hybridization chain reaction (C-HCR) of DNA hairpins (H1 and H2) to form dynamic DNA network.…”

Drug‐grafted DNA as a novel chemogene for targeted combinatorial cancer therapy

“…[9] As such, recently researchers have put large efforts to develop combinatorial drug delivery systems which can not only integrate the advantages of each therapeutic modality, but also strengthen the therapeutic effect in a synergistic way, thus reducing the drug dosage and side effects. [10] In combinatorial therapies against cancer, nucleic acid therapeutics including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) [11][12][13] are frequently employed to suppress the expression of tumor-driven oncogenes or drug-resistance-related proteins, which can further enhance the sensitivity and potency of chemotherapeutics to achieve additive therapeutic effects. [14][15][16] Despite great advances, co-delivery of chemo and gene therapeutics for combinatorial therapy still encounters limitations, including unstable drug packages, potential separation of the drugs during the circulation, and the lack of precise control over the gene and chemo drug ratio.…”