DNA Origami as an In Vivo Drug Delivery Vehicle for Cancer Therapy

Abstract

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.

DNA Nanostructures as Smart Drug-Delivery Vehicles and Molecular Devices

“…Jiang et al [31] and Zhang et al [32] managed to deliver doxorubicin -an anticancer drug and a DNA intercalator -into cells in vivo using rod-like DNA origamis or DNA origami triangles as carriers ( Figure 1B). Zhao et al [33] demonstrated a similar system, except that they used a twisted 3D rod as a vehicle, which enabled tunable release of the doxorubicin molecules ( Figure 1B).…”

“…[4]; Copyright (2006) a box with a switchable lid [6], a tetrahedron [5] and a two-state box [7]. (B) DNA origami nanostructures for delivering doxorubicin (DOX) into cancer cells: an under-twisted rod-like shape [33], a straight rod [31] and a triangle [31,32]. (C) DNA structures for small interfering RNA (siRNA) delivery: a cage with cell-targeting ligands (folate or peptide) at the end of the siRNA motifs [37], and a PEGylated folatemodified nanotube [36].…”

The utility of DNA nanostructures for drug delivery in vivo

“…In agreement with this, the biodistribution analysis shows that the encapsulated DNA origami was primarily in the blood after 2 h and a smaller fraction accumulated in the liver as expected for liposomal delivery. Same year, Zhang and coworkers demonstrated the potential for DNA origami to deliver the chemotherapeutic molecule doxorubicin to tumors in mice [7]. This strategy has been confirmed several times in vitro and plays to the observation that doxorubicin is easily loaded into DNA nanostructures through intercalation.…”

“…Therefore, new methods to probe the structural integrity of DNA nanovehicles in larger animals are needed. The ability of DNA nanovehicles to target tumors appears to depend on their shape [7] and interactions of nanoparticles with complement factors are also shape dependent. Accordingly, future experiments should aim to elucidate this, as it may not only provide valuable insight for DNA nanovehicles, but for drug delivery vehicles in general.…”

3D DNA Crystals and Nanotechnology

“…One potential application that has already been explored with DNA origami constructs is as a drug delivery vehicle. Anti-cancer drugs, such as doxorubicin, can be intercalated into DNA origami designs and used to improve drug efficacy in cell culture models [72,73]. DNA crystals may be suitable for similar use, but with the potential of drugs beyond just small molecule intercalators.…”