Journal
ACS NANO
Volume 8, Issue 7, Pages 6633-6643Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn502058j
Keywords
DNA origami; doxorubicin; in vivo delivery; cancer therapy; fluorescence imaging
Categories
Funding
- National Basic Research Program of China (973 Program) [2012CB934000, 2014CB748600]
- National Key Basic Research and Development Program of China (973 Program) [2011CB707700]
- National Natural Science Foundation of China [81227901, 81090272, 21222311, 91127021]
- National Key Technology Support Program [2012BAI23B06]
- Chinese Academy of Sciences Fellowship for Young International Scientists [2013Y1GB0005]
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Many chemotherapeutics used for cancer treatments encounter issues during delivery to tumors in vivo and may have high levels of systemic toxicity due to their nonspecific distribution. Various materials have been explored to fabricate nanoparticles as drug carriers to Improve delivery efficiency. However, most of these materials suffer from multiple drawbacks, such as limited biocompatibility and inability to engineer spatially addressable surfaces that can be utilized for multifunctional activity. Here, we demonstrate that DNA origami possessed enhanced tumor passive targeting and long-lasting properties at the tumor region. Particularly, the triangle-shaped DNA origami exhibits optimal tumor passive targeting accumulation. The delivery of the known anticancer drug doxorubicin into tumors by self-assembled DNA origami nanostructures was performed, and this approach showed prominent therapeutic efficacy in vivo. The DNA origami carriers were prepared through the self-assembly of M13mp18 phage DNA and hundreds of complementary DNA helper strands; the doxorubicin was subsequently noncovalently intercalated into these nanostructures. After conducting fluorescence imaging and safety evaluation, the doxorubicin-containing DNA origami exhibited remarkable antitumor efficacy without observable systemic toxicity in nude mice bearing orthotopic breast tumors labeled with green fluorescent protein. Our results demonstrated the potential of DNA origami nanostructures as innovative platforms for the efficient and safe drug delivery of cancer therapeutics in vivo.
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