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

• DOI: 10.1021/acsami.0c02957
• Publication Date: 2020-05-20T19:13:54Z
• Authors: Dick Yan Tam; Jonathan Weng-Thi...; Miu Shan Chan; Cia Hin Lau; Tristan Juin Han ...; Hoi Man Leung; Ling Sum Liu; Fei Wang; Leanne Lai Hang Chan; Chung Tin; Pik Kwan Lo
• Keywords: 0301 basic medicine; 0303 health sciences; Nanotubes; Brain Neoplasms; Antineoplastic Agents; Glioma; Xenograft Model Antitumor Assays; 3. Good health; Mice; 03 medical and health sciences; Drug Delivery Systems; Blood-Brain Barrier; Cell Line, Tumor; Animals; Humans; Glioblastoma

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.