@misc{10481/61753,
year = {2020},
url = {http://hdl.handle.net/10481/61753},
abstract = {A controlled synthesis of methotrexate (MTX) silver nanoparticles (AgNPs-MTX) using borohydride and
citrate as reduction and reduction/capping agents, respectively, was performed in order to obtain
AgNPs-MTX conjugates with a narrow size distribution. Their characterization showed polydispersed
spherical shape nanoparticles with a mean size around 13 nm and distribution range between 7–21 nm.
The presence of MTX was confirmed by FTIR and EDX analysis. Spectroscopic determinations suggest
the chemisorption of MTX through a carboxylic group (–COOH) onto AgNPs via the exchange with
a citrate molecule. Drug loading capacities calculated for AgNPs synthesized using different amounts of
MTX were 28, 31 and 40%. In vitro drug release tests depicted similar release profiles for all conjugated
amounts releasing between 77 to 85% of the initial MTX loaded into the AgNPs. With respect to free
MTX, the addition of the nanocarrier delayed its release and also changed its pharmacokinetics. Free
MTX is released after 3 hours following a first order kinetic model, whereas in the presence of AgNPs,
a fast initial release is observed during the first 5 hours, followed by a plateau after 24 hours. In this case,
AgNPs-MTX fitted a Higuchi model, where its solubilization is controlled by a diffusion process. Results
obtained from flow cytometry of different cell lines treated with AgNPs-MTX demonstrated the
combined anticancer effect of both reagents, decreasing the percentage of living cells in a colon cancer
cell line (HTC-116) down to 40% after 48 hours of exposure. This effect was weaker but still significant
for a lung cancer cell line (A-549). Finally, a zebrafish assay with AgNPs-MTX did not show any significant
cytotoxic effect, confirming thereby the reduction of systemic drug toxicity achieved by coupling MTX to
AgNPs. This observed toxicity reduction in the zebrafish model implies also a probable improvement of
the usage of AgNPs-MTX in chemotherapy against human cancers.},
organization = {The authors are grateful for the financial support of the Ministry
of Science and Innovation (CTQ2016-80978-C2-1-R).},
publisher = {The Royal Society of Chemistry},
title = {Synthesis of controlled-size silver nanoparticles for the administration of methotrexate drug and its activity in colon and lung cancer cells},
doi = {10.1039/c9ra08657a},
author = {Rozalen, M. and Sánchez Polo, Manuel and Fernández Perales, M. and Widmann, T. J. and Rivera Utrilla, José},
}