TNA-Mediated Antisense Strategy to Knockdown Akt Genes for Triple-Negative Breast Cancer Therapy.

Triple-negative breast cancer (TNBC) remains a significant challenge in terms of treatment, with limited efficacy of chemotherapy due to side effects and acquired drug resistance. In this study, a threose nucleic acid (TNA)-mediated antisense approach is employed to target therapeutic Akt genes for TNBC therapy. Specifically, two new TNA strands (anti-Akt2 and anti-Akt3) are designed and synthesized that specifically target Akt2 and Akt3 mRNAs.

Targeted brain tumor imaging by using discrete biopolymer-coated nanodiamonds across the blood-brain barrier.

Short circulation lifetime, poor blood-brain barrier (BBB) permeability and low targeting specificity limit nanovehicles from crossing the vascular barrier and reaching the tumor site. Consequently, the precise diagnosis of malignant brain tumors remains a great challenge. This study demonstrates the imaging of photostable biopolymer-coated nanodiamonds (NDs) with tumor targeting properties inside the brain.

Penetrating the Blood-Brain Barrier by Self-Assembled 3D DNA Nanocages as Drug Delivery Vehicles for Brain Cancer Therapy.

The development of biocompatible drug delivery vehicles for cancer therapy in the brain remains a big challenge. In this study, we designed self-assembled DNA nanocages functionalized with or without blood-brain barrier (BBB)-targeting ligands, d and we investigated their penetration across the BBB. Our DNA nanocages were not cytotoxic and they were substantially taken up in brain capillary endothelial cells and Uppsala 87 malignant glioma (U-87 MG) cells.

Reversible reconfiguration of high-order DNA nanostructures by employing G-quartet toeholds as adhesive units.

G-quadruplex structures are becoming useful alternative interaction modules for the assembly of DNA nanomaterials because of their unique inducibility by cations. In this study, we demonstrated a new strategy for the assembly of polymeric DNA nanoarchitectures in the presence of cations, such as K and Na, by employing G-quartet toeholds at the edges of discrete mini-square DNA building blocks as adhesive units. In comparison with the Watson-Crick base-paired duplex linkers, G-quadruplex arrays embedded in the self-assembled DNA system exhibit higher thermal stability.

Synthetic α-l-Threose Nucleic Acids Targeting BcL-2 Show Gene Silencing and in Vivo Antitumor Activity for Cancer Therapy.

We design and synthesize a sequence-defined α-l-threose nucleic acid (TNA) polymer, which is complementary to certain nucleotide sites of target anti-apoptotic proteins, BcL-2 involving in development and progression of tumors. Compared to scramble TNA, anti-BcL-2 TNA significantly suppresses target mRNA and protein expression in cancerous cells and shows antitumor activity in carcinoma xenografts, resulting in suppression of tumor cell growth and induction of tumor cell death. Together with good biocompatibility, very low toxicity, excellent specificity features, and strong binding affinity toward the complementary target RNAs, TNAs become new useful biomaterials and effective alternatives to traditional antisense oligonucleotides including locked nucleic acids, morpholino oligomers, and peptide nucleic acids in antisense therapy.