Eu-Doped Citrate-Coated Carbonated Apatite Luminescent Nanoprobes for Drug Delivery

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.

Crystallization, Luminescence and Cytocompatibility of Hexagonal Calcium Doped Terbium Phosphate Hydrate Nanoparticles

“…The analysis of CSD and ζ-potential versus pH of aqueous suspensions of the nanoparticles is also relevant to assess their potential as luminescent probes in nanomedicine applications. The tendency of the colloid to disperse or aggregate in simulated physiological conditions in the blood (pH around 7.4) or in the tumor microenvironment (pH around 5-6) are related to the size and surface charge of the nanoparticles [16,46]. In addition, these features have an impact on the formation of the protein corona around the nanoparticles [47].…”

Biocompatible Multifunctional Theranostic Nanoprobe for Imaging and Chemotherapy in Solid‐Tumor‐Bearing Mice

“…Drug loading was followed by measuring absorbance of supernatant at 480 nm, before and after encapsulation using JASCO‐L‐670 spectrophotometer. Difference in absorbance gave the quantity of drug encapsulated [4,28] …”

“…dox‐loaded PEGylated polymer capsules were dispersed in 7 mL buffered saline of corresponding pH and aliquoted into seven equal fractions. Each fraction was centrifuged at various time periods and fluorescence of supernatant was measured (λ ex =480 nm; λ em =560 nm) [4,29] …”

“…along with therapeutic molecule (e. g. drugs, proteins, genes etc.). Many nanomaterials‐based theranostic agents such as metallic [1,2] (e. g. gold, silver), [2] inorganic (e. g. iron oxide, lanthanide ion doped nanoparticles), [3–11] polymeric [12] (e. g. polylactone, [13] carboxylated poly [styrene‐co‐chloromethyl styrene]‐graft‐poly ethylene glycol [14] ), carbon‐based (e. g. graphene, carbon nanotubes, carbon dot), [15,16] aggregation‐induced emission (AIE) dots [17,18] and mesoporous (e. g. mesoporous silica, mesoporous glasses) [19–21] nanomaterials have been explored. Among the above, materials possessing fluorescence as a diagnosis probe is popular since fluorescence imaging provides high sensitivity and can also be used for molecular imaging [22] .…”

Synthesis and Biomedical Applications of Lanthanides-Doped Persistent Luminescence Phosphors With NIR Emissions

“…In addition to bioimaging, PLPs can also be used as drug carriers to construct a bioimaging-guided drug delivery system (Zhang D. et al, 2018 ). Previous studies have shown that folate-modified PLPs can precisely target tumor cells, so the researchers attempted to load the PLPs with anti-tumor drugs to treat tumors in situ (Jabalera et al, 2020 ). Shi et al synthesized the PLP probe Zn 1.1 Ga 1.8 Ge 0.1 O 4 :Cr 3+ ,Eu 3+ @SiO 2 with a 696 nm emission (Shi et al, 2015 ).…”