posted on 2020-06-19, 12:03authored byDick Yan Tam, Jonathan Weng-Thim Ho, Miu Shan Chan, Cia Hin Lau, Tristan Juin Han Chang, Hoi Man Leung, Ling Sum Liu, Fei Wang, Leanne Lai Hang Chan, Chung Tin, Pik Kwan Lo
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. We found that ligand modification
is not essential for this DNA system as the ligand-free DNA nanocages
(LF-NCs) could still cross the BBB by endocytosis inin vitro and in vivo models. Our spherical DNA nanocages
were more permeable across the BBB compared with tubular DNA nanotubes.
Remarkably, in vivo studies revealed that DNA nanocages
could carry anticancer drugs across the BBB and inhibit the tumor
growth in a U-87 MG xenograft mouse model. This is the first example
showing the potential of DNA nanocages as innovative delivery vehicles
to the brain for cancer therapy. Unlike other delivery systems, our
work suggest that a DNA nanocage-based platform provides a safe and
cost-effective tool for targeted delivery to the brain and therapy
for brain tumors.