Abstract
In the field of Nanomedicine, there is an increasing demand for new inorganic nanophosphors with low cytotoxicity and efficient loading-release ability of drugs for applications in bioimaging and drug delivery. This work assesses the potentiality of matured Eu-doped citrate-coated carbonated apatite nanoparticles to be used as theranostic platforms, for bioimaging, as luminescent nanoprobes, and for drug delivery applications, using Doxorubicin as a model drug. The drug adsorption isotherm fits the Langmuir–Freundlich (LF) model, showing that the Eu:cit-cAp nanoparticles can carry a maximum of 0.29 ± 0.02 mg Doxo mg Eu:cit-cAp−1 (Qmax). The affinity constant KFL for this binding is 44 ± 2 mL mg−1, and the cooperativity coefficient r is 6 ± 1. The nanoparticle suspensions presented charge reversion from negative to positive after loading with Doxo as revealed by the ζ-potential versus pH characterization. The release of drug from the loaded nanoparticles was found to be strongly pH-dependent, being around 5 wt % at physiological pH 7.4 and 20 wt % at pH 5, in experiments lasting 24 h. Luminescence spectroscopic measurements of Doxo-loaded nanoparticles revealed the increase of luminescence with a decrease in the amount of adsorbed Doxo, due to the so-called inner filter effect. The nanoparticles free of Doxo were cytocompatible when interacted with two human cell lines derived respectively from a gastric carcinoma (GTL-16), and a hepatocarcinoma (Huh7), while Doxo-loaded nanoparticles displayed significant toxicity in a dose-dependent relationship. Therefore, the new nanoassemblies might have a dual function, as nanoprobes in bioimaging by detecting the fate of the nanoparticles in biological environments, and for monitoring the delivery of the drug in such environments, by measuring the rise of the luminescence provided by the desorption of Doxo.
Highlights
For more than 10–15 years, nanoparticles (NPs) are offering new opportunities in different fields, including medicine, namely because they can act as multifunctional platforms for both diagnostic and therapeutic applications [1,2,3]
This work assesses the potentiality of matured europium doped carbonated apatite (Eu)-doped citrate-coated carbonated apatite nanoparticles to be used as theranostic platforms, for bioimaging, as luminescent nanoprobes, and for drug delivery applications, using Doxorubicin as a model drug
As Eu:cit-cAp was already demonstrated to be a good nanophosphor [27], we have studied its drug delivery ability, using Doxo as a model
Summary
For more than 10–15 years, nanoparticles (NPs) are offering new opportunities in different fields, including medicine, namely because they can act as multifunctional platforms for both diagnostic and therapeutic applications [1,2,3]. Apatite can be functionalized with different molecules, which can be released in response to local stimuli, e.g., a change in pH [18,19,20] Because of these special features, lanthanide-doped apatite nanoparticles are excellent candidates as theranostic platforms, i.e., for bioimaging and for drug delivery applications [21,22,23,24,25,26]. We have prepared biomimetic (bone-like) citrate-coated europium doped carbonated apatite (Eu:cit-cAp) nanoparticles as well as citrate-coated calcium doped europium phosphate monohydrate (Ca:cit-EuPO4·H2O, rhabdophane type) nanophosphors [27,28] at different cation doping concentrations and maturation times by the citrate-based thermal decomplexing method [29,30]. Release as a function of pH, stability of the aqueous suspensions, effect of the loaded drug on nanoparticle luminescence properties, as well as the cytotoxicity of the drug-loaded nanoparticles in in vitro assays against two human cell lines derived respectively from a gastric carcinoma (GTL-16), and a hepatocarcinoma (Huh7), were analyzed
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