We developed hybrid nanospheres comprised of two of the
most important
biomolecules in nature, DNA and proteins, which have excellent biocompatibility,
high drug payload capacity, in vivo imaging ability,
and in vitro/in vivo cancer targeting
capability. The synthesis can be done in a facile one-pot assembly
system that includes three steps: step-growth polymerization of two
DNA oligomers, addition of streptavidin to assemble spherical hybrid
nanostructures, and functionalization of hybrid nanospheres with biotinylated
aptamers. To test the feasibility of cancer targeting and drug-loading
capacity of the hybrid nanospheres, MUC1-specific aptamers (MA3) were
conjugated to nanosphere surfaces (apt-nanospheres), and doxorubicin
(Dox) was loaded into nanospheres by DNA intercalation. The successful
construction of nanospheres and apt-nanospheres was confirmed by agarose
gel electrophoresis and dynamic light scattering (DLS). Their uniform
spherical morphology was confirmed by transmission electron microscopy
(TEM). Fluorescence spectra of nanospheres demonstrated high Dox-loading
capability and slow-release characteristics. In vitro MUC1-specific binding of the apt-nanospheres was confirmed by flow
cytometry and confocal microscopy. Dox-loaded apt-nanospheres significantly
increased cytotoxicity of the MUC1-positive cancer cells due to aptamer-mediated
selective internalization, as shown via cell viability assays. Apt-nanospheres
could also be imaged in vivo through the synthesis
of hybrid nanospheres using fluorescent dye-conjugated DNA strands.
Finally, in vivo specific targeting ability of apt-nanospheres
was confirmed in a MUC1-positive 4T1 tumor-bearing mouse model, whereas
apt-nanospheres did not cause any sign of systemic toxicity in normal
mice. Taken together, our self-assembled DNA–streptavidin hybrid
nanospheres show promise as a biocompatible cancer targeting material
for contemporary nanomedical technology.
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