We present the synthesis of amorphous, mesoporous, colloidal magnesium phosphate-citrate nanoparticles (MPCs) from biogenic precursors, resulting in a biocompatible and biodegradable nanocarrier that amplifies the action of the anticancer drug methotrexate (MTX). Synthesis conditions were gradually tuned to investigate the influence of the chelating agent citric acid on the colloidal stability and the mesoporosity of the obtained nanoparticles. With optimized synthesis conditions, a large BET surface area of 560 m2/g was achieved. We demonstrate the potential of these biocompatible and biodegradable mesoporous MPCs as a drug delivery system. Lipid-coated MPCs were used to load the fluorescent dye calcein and the chemotherapeutic agent MTX into the mesopores. In vitro experiments show very low premature release of the cargo but efficient stimuli-responsive release in an environment of pH 5.5, in which MPCs degrade. Lipid-coated MPCs are taken up by cancer cells and are nontoxic up to concentrations of 100 μg/mL. When loaded with MTX serving as a representative model drug for in vitro studies, MPCs induced efficient cell death with an IC50 value of 1.1 μg/mL. Compared to free MTX, its delivery with MPCs enhances its efficiency by an order of magnitude. In summary, we have developed a biodegradable nanomaterial synthesized from biocompatible precursors that are neither toxic by themselves nor in the form of nanoparticles. With these features, MPCs may be applied as drug delivery systems and have the potential to reduce the side effects of current chemotherapies.
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