DNA‐doxorubicin interaction: New insights and peculiarities

We have investigated the interaction of the DNA molecule with the anticancer drug doxorubicin (doxo) by using three different experimental techniques: single molecule stretching, single molecule imaging, and dynamic light scattering. Such techniques allowed us to get new insights on the mechanical b...

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Bibliographic Details
Published in:Biopolymers 2017-03, Vol.107 (3), p.np-n/a
Main Authors: Silva, E. F., Bazoni, R. F., Ramos, E. B., Rocha, M. S.
Format: Article
Language:English
Subjects:
Agglomeration
Buffers (chemistry)
Deoxyribonucleic acid
DNA - chemistry
DNA - metabolism
DNA Adducts - chemistry
doxorubicin
Doxorubicin - chemistry
Doxorubicin - metabolism
Dynamic Light Scattering
Imaging
Light scattering
mechanical properties
Microscopy, Atomic Force
Optical Tweezers
Physical chemistry
single molecule
Strength
Stretching
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Summary:We have investigated the interaction of the DNA molecule with the anticancer drug doxorubicin (doxo) by using three different experimental techniques: single molecule stretching, single molecule imaging, and dynamic light scattering. Such techniques allowed us to get new insights on the mechanical behavior of the DNA‐doxo complexes as well as on the physical chemistry of the interaction. First, the contour length data obtained from single molecule stretching were used to extract the physicochemical parameters of the DNA‐doxo interaction under different buffer conditions. This analysis has proven that the physical chemistry of such interaction can be modulated by changing the ionic strength of the surrounding buffer. In particular we have found that at low ionc strengths doxo interacts with DNA by simple intercalation (no aggregation) and/or by forming bound dimers. For high ionic strengths, otherwise, doxo‐doxo self‐association is enhanced, giving rise to the formation of bound doxo aggregates composed by 3 to 4 molecules along the double‐helix. On the other hand, the results obtained for the persistence length of the DNA‐doxo complexes is strongly force‐dependent, presenting different behaviors when measured with stretching or non‐stretching techniques.
ISSN:0006-3525
1097-0282
DOI:10.1002/bip.22998