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

2020 
: Development of biocompatible drug delivery vehicles for cancer therapy in brain remains a big challenge. In this study, self-assembled DNA nanocages functionalized with or without blood-brain barrier (BBB) targeting ligands were designed and investigated for BBB penetration. They showed no cytotoxicity, and substantial uptake in brain capillary endothelial cells and Uppsala 87 malignant glioma (U-87 MG) cells. It is found that ligand modification is not essential for this DNA system. The ligand-free DNA nanocages (LF-NCs) could still cross the BBB by endocytosis both in vitro and in vivo. These spherical DNA nanocages exhibited much better BBB permeability than tubular DNA nanotubes. Remarkably, in vivo studies revealed that DNA nanocages could carry the anticancer drugs across the BBB and inhibit the tumor growth in U-87 MG xenograft in nude mice. This is the first example showing the potential of DNA nanocages as innovative delivery vehicle in brain for cancer therapy. Unlike other delivery systems, our work suggests that DNA nanocage-based platform provides a safe and cost-effective tool for targeted delivery in brain and therapy of brain tumor.
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