Cano Plá Sandra Maria, D'Urso Annarita, Fernández-Sánchez Jorge Fernando, Colangelo Donato, Choquesillo-Lazarte Duane, Ferracini Riccardo, Bosetti Michela, Prat Maria, Gómez-Morales Jaime
Laboratorio de Estudios Cristalográficos, IACT, CSIC-UGR, Avda. Las Palmeras, n° 4, E-18100 Granada, Spain.
Dipartimento di Scienze della Salute, Università del Piemonte Orientale, "A. Avogadro" Via Solaroli, 17, 28100 Novara, Italy.
Nanomaterials (Basel). 2022 Feb 6;12(3):562. doi: 10.3390/nano12030562.
Luminescent nanoparticles are innovative tools for medicine, allowing the imaging of cells and tissues, and, at the same time, carrying and releasing different types of molecules. We explored and compared the loading/release ability of diclofenac (COX-2 antagonist), in both undoped- and luminescent Terbium (Tb)-doped citrate-coated carbonated apatite nanoparticles at different temperatures (25, 37, 40 °C) and pHs (7.4, 5.2). The cytocompatibility was evaluated on two osteosarcoma cell lines and primary human osteoblasts. Biological effects of diclofenac-loaded-nanoparticles were monitored in an in vitro osteoblast's cytokine-induced inflammation model by evaluating COX-2 mRNA expression and production of PGE. Adsorption isotherms fitted the multilayer Langmuir-Freundlich model. The maximum adsorbed amounts at 37 °C were higher than at 25 °C, and particularly when using the Tb -doped particles. Diclofenac-release efficiencies were higher at pH 5.2, a condition simulating a local inflammation. The luminescence properties of diclofenac-loaded Tb -doped particles were affected by pH, being the relative luminescence intensity higher at pH 5.2 and the luminescence lifetime higher at pH 7.4, but not influenced either by the temperature or by the diclofenac-loaded amount. Both undoped and Tb-doped nanoparticles were cytocompatible. In addition, diclofenac release increased COX-2 mRNA expression and decreased PGE production in an in vitro inflammation model. These findings evidence the potential of these nanoparticles for osteo-localized delivery of anti-inflammatory drugs and the possibility to localize the inflammation, characterized by a decrease in pH, by changes in luminescence.
发光纳米颗粒是医学领域的创新工具，可用于细胞和组织成像，同时还能携带和释放不同类型的分子。我们探究并比较了双氯芬酸（一种COX-2拮抗剂）在未掺杂和掺有发光铽（Tb）的柠檬酸盐包覆的碳酸化磷灰石纳米颗粒中的负载/释放能力，实验条件为不同温度（25、37、40°C）和不同pH值（7.4、5.2）。我们对两种骨肉瘤细胞系和原代人成骨细胞进行了细胞相容性评估。在体外成骨细胞细胞因子诱导的炎症模型中，通过评估COX-2 mRNA表达和PGE的产生，监测了负载双氯芬酸纳米颗粒的生物学效应。吸附等温线符合多层朗缪尔-弗伦德里希模型。37°C时的最大吸附量高于25°C时，特别是使用掺Tb颗粒时。在模拟局部炎症的pH 5.2条件下，双氯芬酸的释放效率更高。负载双氯芬酸的掺Tb颗粒的发光特性受pH影响，pH 5.2时相对发光强度较高，pH 7.4时发光寿命较长，但不受温度或双氯芬酸负载量的影响。未掺杂和掺Tb的纳米颗粒均具有细胞相容性。此外，在体外炎症模型中，双氯芬酸的释放增加了COX-2 mRNA表达并降低了PGE的产生。这些发现证明了这些纳米颗粒在骨局部递送抗炎药物方面的潜力，以及通过发光变化来定位以pH降低为特征的炎症的可能性。
