title: DNA-doxorubicin interaction: New insights and peculiarities.
abstract: 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.
authors.affiliation: Laboratório de Física Biológica, Departamento de Física, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: E F
authors.initials: EF
authors.lastname: Silva
authors.affiliation: Laboratório de Física Biológica, Departamento de Física, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: R F
authors.initials: RF
authors.lastname: Bazoni
authors.affiliation: Laboratório de Física Biológica, Departamento de Física, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: E B
authors.initials: EB
authors.lastname: Ramos
authors.affiliation: Laboratório de Física Biológica, Departamento de Física, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: M S
authors.initials: MS
authors.lastname: Rocha
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D018736:DNA Adducts / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry* / Q000378:metabolism; D000067493:Dynamic Light Scattering; D018625:Microscopy, Atomic Force; D052898:Optical Tweezers
chemical_list: D018736:DNA Adducts; C031902:doxorubicin-DNA; D004317:Doxorubicin; D004247:DNA
keywords: doxorubicin; mechanical properties; physical chemistry; single molecule