Angewandte Chemie International Edition
10.1002/anie.201706301
COMMUNICATION
liver, lung, and kidneys) in the F and F-S treated groups have
well-defined cytoplasm and nuclei and show almost the same
features as those of the PBS control group. Only sporadic
nuclear shrinkage (pyknosis) appears (Figure 3E and Figure S8).
In contrast, obvious nuclear shrinkage of cancer cells is
observed in the F-buckyball treated group but all other major
organs show no tissue damage (Figure 3E and Figure S8).
Again, these results confirm that F-buckyball is the most efficient
one for anticancer therapy with no obvious side effects.
Moreover, the terminal transferase-mediated dUTP nick end-
labeling (TUNEL) staining demonstrates that the green
fluorescent signal in nuclei of F-buckyball treated group is much
stronger than those of free F and F-S treated groups (Figure 3E).
This result verifies that F-buckyball indeed induces more cell
apoptosis and exhibits higher antitumor efficacy, which is
consistent with the H&E staining. The improved therapeutic
efficacy of F-buckyball Trojan Horse may be partially attributed
to its passive targeting ability aroused by a suitable size in
nanoscale. In addition, DNA Trojan Horses also contain a
multitude of polymeric floxuridine segments, which could be
generated by enzymatic degradation. It has been reported that
polymeric form of floxuridine has significantly higher cytotoxicity
than free floxuridine in terms of inhibiting the growth of tumor
cells.[25] Taken together, it may explain the excellence of DNA
Trojan horses (herein the F-buckyball) in antitumor evaluation.
In summary, as the Greeks did in the Trojan War, we
demonstrated that anticancer drugs could be tactfully hidden in
DNA strands to construct Trojan Horse like DDSs for the fight
against cancer. Upon integrating with nucleoside analogues,
molecular recognition capability of the new strands remained as
the same as conventional DNAs, enabling the syntheses of well-
defined drug-containing nanostructures via the tile-based self-
assembly. As such, the drug loading ratios and morphologies of
DNA Trojan Horses could be accurately controlled according to
their sequence information. Importantly, we found that the
morphology of DNA Trojan Horses could strongly affect their
cellular uptake behaviors. Among them, drug-containing
buckyball showed as the most effective one for drug delivery
and inhibiting the growth of tumor cells both in vitro and in vivo.
As many other nucleoside analogues can be integrated into
DNA strands and then assemble into well-defined
nanostructures, these DNA Trojan Horses with precise drug
loading ratio, tunable size and morphology raise a new idea of
precise nanodrugs for a better cancer therapy.
The authors declare no conflict of interest.
Keywords: DNA nanotechnology • precise nanodrugs • drug
delivery • cancer therapy • nucleoside analogues
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Conflict of interest
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