Influence of a magnetic nanoparticle as a drug carrier on the activity of anticancer drugs: interactions of double stranded DNA and doxorubicin modified with a carrier.
Magnetic drug targeting executed by nanoparticles as carriers is a promising cancer treatment which avoids the side effects of conventional chemotherapy. We have modified doxorubicin with magnetic nanoparticles. Doxorubicin (adriamycin) is a potential anticancer drug yet nonspecific in its antibiotic action. Therefore, carriers for tissue-specific, targeted drug delivery are of utmost importance. We report here on the interaction of doxorubicin covalently bound via tether molecules to colloidal magnetic nanoparticles (ferrofluid) with calf thymus double stranded DNA (dsDNA). By means of spectroscopic and electrochemical techniques, we have shown that appropriate length and flexibility of tether molecules allows the preservation of essentially intact intercalation capabilities of free doxorubicin in the solution. In order to evaluate these capabilities, we have studied the binding constant of doxorubicin attached to nanoferrites with dsDNA as well as the binding site size on the dsDNA molecule. The binding constant decreased slightly compared to that of free doxorubicin while the binding site size, describing the number of consecutive DNA lattice residues involved in the binding, increased. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) images were also obtained to support the conclusion on the interactions between doxorubicin-modified magnetic nanoparticles and dsDNA.
Nowicka
Anna M
AM
Department of Chemistry, University of Warsaw, ul. Pasteura 1, PL-02-093 Warsaw. anowicka@chem.uw.edu.pl
Kowalczyk
Agata
A
Donten
Mikolaj
M
Krysinski
Pawel
P
Stojek
Zbigniew
Z
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism*; D004337:Drug Carriers; D008280:Magnetics; D053758:Nanoparticles
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D004317:Doxorubicin; D004247:DNA; C427203:calf thymus DNA