Angewandte Chemie International Edition
10.1002/anie.201809753
COMMUNICATION
prepared by straightforward one-step SCVP. An aptamer was
efficiently conjugated with the hyperbranched polymer by
bioorthogonal click chemistry, allowing unfettered functionality of
both aptamer and polymer. Self-assembled nanoparticles
sustained colloidal stability and homogeneous distribution owing
to the negatively charged DNA shell. Moreover, efficient loading,
externally-triggered controllable release, and rapid release
kinetics were observed for the model drug, NR. In vitro cell study
demonstrated excellent binding to target cancer cells and cellular
uptake behavior. DOX-loaded HDNPs significantly inhibited tumor
cell proliferation, but only in the presence of aptamer sgc8-grafted
HDNP and only when external UV stimulus was imposed. By
achieving targeted drug delivery and remote pulsatile drug
release, this photoresponsive DNA aptamer-hyperbranched
polymer nanoassembly could act as an efficient drug delivery
platform, highlighting its immense potential in cancer therapy.
Acknowledgements
Figure 3. (A) Cell-binding test of HDNP by flow cytometry; (B) Cell
internalization test of HDNP by Confocal microscopy; (C) Cytotoxicity of DOX-
loaded HDNP-sgc8/Library with and w/o UV light.
This work is supported by NIH GM R35 127130 and NSF 1645215,
DMR-1606410, and by NSFC grants (NSFC 21521063).
Prior to the cytotoxicity study with HDNP-sgc8, the maximum
exposure time of CEM cells under UV light was determined to
ensure a safe threshold of irradiation. As shown in Figure S15, no
reduction of cell viability was observed in the first 20 min (Figure
S19). On the other hand, UV-triggered release of NR was
instantaneous, resulting in the release of more than 70% of Nile
Red within 20 min (Figure 2D). Therefore, the UV irradiation time
was set to 15 min to achieve greater nanoparticle disassembly
and significant drug release without cell damage. To verify the
material’s intrinsic safety and biocompatibility, CEM cells were
cultured with medium containing different concentrations of
HDNP-sgc8 followed by 15 min of UV irradiation. As shown in
Figure S20, no toxicity was observed, even at a high dose of 200
μg/mL.
Keywords: self-assemble • hyperbranched polymer •
photoresponsive • aptamer • drug delivery
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In conclusion, we have, for the first time, developed a selective
targeting and light-controlled drug delivery nanostructure formed
by self-assembly of
a
DNA-grafted polymer.
A
new
photoresponsive and hyperbranched polymer was designed and
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