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Superparamagnetic iron-doped nanocrystalline apatite as a delivery system for doxorubicin
Author(s) -
Michele Iafisco,
Christophe Drouet,
Alessio Adamiano,
Patricia Pascaud,
Monica Montesi,
Silvia Panseri,
Stéphanie Sarda,
Anna Tampieri
Publication year - 2015
Publication title -
journal of materials chemistry b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 101
eISSN - 2050-7518
pISSN - 2050-750X
DOI - 10.1039/c5tb01524c
Subject(s) - superparamagnetism , apatite , doxorubicin , adsorption , drug delivery , materials science , nanoparticle , biomolecule , nanotechnology , magnetic nanoparticles , chemical engineering , nanocrystalline material , surface modification , chemistry , nuclear chemistry , biophysics , organic chemistry , magnetization , mineralogy , magnetic field , biology , medicine , physics , surgery , chemotherapy , quantum mechanics , engineering
The development of non-toxic and biodegradable magnetic nanoparticles (NPs) that can be easily functionalized with drugs or biomolecules and employed, under magnetic fields, as targeted nano-carriers or components of scaffolds with on-demand functionalities, is a big challenge in the biomaterials research. In the present work, the feasibility of previously synthesized iron-doped superparamagnetic apatite (FeHA) NPs to bind and then release the anticancer drug doxorubicin (DOX) under an applied low-frequency pulsed electromagnetic field (PEMF) was investigated. The behavior of FeHA towards DOX has been compared to that of synthetic biomimetic apatite (HA) NPs prepared ad hoc with characteristics close to those of bone mineral. The DOX adsorption kinetics and isotherms on FeHA and HA were explored and fitted according to different mathematical models (Elovich, Sips and Freundlich) revealing enhanced uptake of DOX on FeHA than HA, due to the better interaction of the drug with the surface iron cations and formation of multi-molecular DOX assemblies. In the absence of the PEMF, the quantity of DOX released from HA was higher than that released from FeHA, in agreement with the lower affinity of DOX for HA than FeHA. Interestingly, in the presence of the PEMF, the extent of DOX released from FeHA after 3 and 6 days increased significantly. The higher DOX release from FeHA under PEMF can be explained by the mechanical shacking of superparamagnetic FeHA NPs breaking the bonding with the drug and allowing detachment of DOX assemblies from the NP surface. In vitro assays demonstrated that DOX loaded on HA and FeHA displayed cytotoxicity against the human osteosarcoma cell line (SAOS-2) at the same level as free DOX, for all the concentrations and time points tested. Confocal microscopy analyses showed that drug-loaded NPs were rapidly internalized within cells and released DOX, which accumulated in the nuclei where it exerted the desired cytotoxic activity.

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