Supramolecular aptamer nano-constructs for receptor-mediated targeting and light-triggered release of chemotherapeutics into cancer cells

Deepak K. Prusty, Volker Adam, Reza M. Zadegan, Stephan Irsen and Michael Famulok ()
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Deepak K. Prusty: Chemical Biology & Medicinal Chemistry Unit, c/o Kekulé Institute of Organic Chemistry and Biochemistry
Volker Adam: Chemical Biology & Medicinal Chemistry Unit, c/o Kekulé Institute of Organic Chemistry and Biochemistry
Reza M. Zadegan: Boise State University
Stephan Irsen: Elektronenmikroskopie und Analytik
Michael Famulok: Chemical Biology & Medicinal Chemistry Unit, c/o Kekulé Institute of Organic Chemistry and Biochemistry

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract Platforms for targeted drug-delivery must simultaneously exhibit serum stability, efficient directed cell internalization, and triggered drug release. Here, using lipid-mediated self-assembly of aptamers, we combine multiple structural motifs into a single nanoconstruct that targets hepatocyte growth factor receptor (cMet). The nanocarrier consists of lipidated versions of a cMet-binding aptamer and a separate lipidated GC-rich DNA hairpin motif loaded with intercalated doxorubicin. Multiple 2′,6′-dimethylazobenzene moieties are incorporated into the doxorubicin-binding motif to trigger the release of the chemotherapeutics by photoisomerization. The lipidated DNA scaffolds self-assemble into spherical hybrid-nanoconstructs that specifically bind cMet. The combined features of the nanocarriers increase serum nuclease resistance, favor their import into cells presumably mediated by endocytosis, and allow selective photo-release of the chemotherapeutic into the targeted cells. cMet-expressing H1838 tumor cells specifically internalize drug-loaded nanoconstructs, and subsequent UV exposure enhances cell mortality. This modular approach thus paves the way for novel classes of powerful aptamer-based therapeutics.

Date: 2018
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DOI: 10.1038/s41467-018-02929-2

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