Scientific article

One nanometer self-assembled aptamer-DNA dendrimers carry 350 doxorubicin: super-stability and intra-nuclear DNA comet tail

Published inChemical Engineering Journal, vol. 388, 124170
Publication date2020

Recent development of aptamer-nanomaterial assemblies witnesses a great success. However, the instability and off-target imperfection of the aptamer-nanomaterial assemblies still need to be improved for clinical theranostic development. Here, we show the aptamer sgc8-hybridized DNA dendrimers with engineering simplicity, robust biostability and target specificity. We introduced a trigger to a mixture of intelligently-designed oligonucleotides to initiate programmable hybridization/polymerization process that was controlled by substrates/byproducts equilibration cycles, yielding nick-sealed sgc8DNA dendrimers after ligation with sgc8-Linkers. The molecular entity and biostability, targeting specificity and theranostic efficacy of the sgc8-DNA dendrimers were characterized by physicochemistry, molecular and cellular biology and in vivo models. The DNA dendrimers showed super-stability in FBS-containing culture medium or in serum for more than 36 h and were resistant to 100 °C-annealing and physiological DNase. The sgc8-DNA dendrimers specifically distinguished target CCRF-CEM cells from the cognate ones, and bound to CCRF-CEM even in the presence of many interfering cells or in blood. The highly-branched dendrimers provided huge surface interfaces to load doxorubicin by G-C hybrids at a molar ratio over 350, and specifically delivered doxorubicin to nuclei of CCRF-CEM evidenced by DNA synthesis arrest and comet tail, thus preventing doxorubicin's non-selective cytotoxicity. The sgc8-DNA dendrimers showed specific capturing of circulating CCRF-CEM cells and in vivo theranostic effects on implanted tumors. The novel and stable sgc8-DNA dendrimers with high pay-load may be best-suited for cancer theranostics.

Affiliation Not a UNIGE publication
Citation (ISO format)
LE, Jingqing et al. One nanometer self-assembled aptamer-DNA dendrimers carry 350 doxorubicin: super-stability and intra-nuclear DNA comet tail. In: Chemical Engineering Journal, 2020, vol. 388, p. 124170. doi: 10.1016/j.cej.2020.124170
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Article (Published version)
ISSN of the journal1385-8947

Technical informations

Creation10/12/2020 2:55:00 PM
First validation10/12/2020 2:55:00 PM
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