Biodegradable CpG DNA hydrogels for sustained delivery of doxorubicin and immunostimulatory signals in tumor-bearing mice

Immunostimulatory CpG DNA was self-assembled to form DNA hydrogels for use as a sustained delivery system for both intercalated doxorubicin (DXR) and immunostimulatory CpG motifs for cancer treatment X-shaped DNA (X-DNA) was designed as a building unit and underwent ligation to form DNA hydrogels Two types of X-DNA were constructed using four oligodeoxynucleotides each one containing six potent CpG motifs (CpG X-DNA) and the other with none (CpG-free X-DNA) CpG X-DNA was more effective than its components or the CpG-free counterpart in terms of the production of tumor necrosis factor-alpha from murine macrophage-like RAW264 7 cells as well as maturation of the murine dendritic DC2 4 cells The cytotoxic effects of X-DNA DXR and their complexes were examined in a co-culture system of colon26/Luc cells a murine adenocarcinoma clone stably expressing firefly luciferase and RAW264 7 cells DXR/CpG X-DNA showed the highest ability to inhibit the proliferation of colon26/Luc cells DXR was slowly released from CpG DNA hydrogels Injections of DXR/CpG DNA hydrogels into a subcutaneous colon26 tumor effectively inhibited tumor growth These results show that CpG DNA hydrogels are an effective sustained system for delivery of immunostimulatory signals to TLR9-positive immune cells and DXR to cancer cells (C) 2010 Elsevier Ltd All rights reserved