Iafisco Michele, Drouet Christophe, Adamiano Alessio, Pascaud Patricia, Montesi Monica, Panseri Silvia, Sarda Stephanie, Tampieri Anna
Institute of Science and Technology for Ceramics (ISTEC), National Research Council (CNR), Via Granarolo 64, 48018 Faenza (RA), Italy.
J Mater Chem B. 2016 Jan 7;4(1):57-70. doi: 10.1039/c5tb01524c. Epub 2015 Nov 27.
The development of non-toxic and biodegradable magnetic nanoparticles (NPs) that can be easily functionalized with drugs or biomolecules and employed, under magnetic fields, as targeted nano-carriers or components of scaffolds with on-demand functionalities, is a big challenge in the biomaterials research. In the present work, the feasibility of previously synthesized iron-doped superparamagnetic apatite (FeHA) NPs to bind and then release the anticancer drug doxorubicin (DOX) under an applied low-frequency pulsed electromagnetic field (PEMF) was investigated. The behavior of FeHA towards DOX has been compared to that of synthetic biomimetic apatite (HA) NPs prepared ad hoc with characteristics close to those of bone mineral. The DOX adsorption kinetics and isotherms on FeHA and HA were explored and fitted according to different mathematical models (Elovich, Sips and Freundlich) revealing enhanced uptake of DOX on FeHA than HA, due to the better interaction of the drug with the surface iron cations and formation of multi-molecular DOX assemblies. In the absence of the PEMF, the quantity of DOX released from HA was higher than that released from FeHA, in agreement with the lower affinity of DOX for HA than FeHA. Interestingly, in the presence of the PEMF, the extent of DOX released from FeHA after 3 and 6 days increased significantly. The higher DOX release from FeHA under PEMF can be explained by the mechanical shacking of superparamagnetic FeHA NPs breaking the bonding with the drug and allowing detachment of DOX assemblies from the NP surface. In vitro assays demonstrated that DOX loaded on HA and FeHA displayed cytotoxicity against the human osteosarcoma cell line (SAOS-2) at the same level as free DOX, for all the concentrations and time points tested. Confocal microscopy analyses showed that drug-loaded NPs were rapidly internalized within cells and released DOX, which accumulated in the nuclei where it exerted the desired cytotoxic activity.
开发无毒且可生物降解的磁性纳米颗粒（NPs）是生物材料研究中的一项重大挑战，这种纳米颗粒能够轻松地用药物或生物分子进行功能化，并在磁场作用下用作靶向纳米载体或具有按需功能的支架组件。在本研究中，研究了先前合成的铁掺杂超顺磁性磷灰石（FeHA）纳米颗粒在施加的低频脉冲电磁场（PEMF）下结合并随后释放抗癌药物阿霉素（DOX）的可行性。将FeHA对DOX的行为与专门制备的具有接近骨矿物质特性的合成仿生磷灰石（HA）纳米颗粒的行为进行了比较。根据不同的数学模型（Elovich、Sips和Freundlich）探索并拟合了DOX在FeHA和HA上的吸附动力学和等温线，结果表明由于药物与表面铁阳离子的更好相互作用以及多分子DOX聚集体的形成，DOX在FeHA上的摄取比在HA上增强。在没有PEMF的情况下，从HA释放的DOX量高于从FeHA释放的量，这与DOX对HA的亲和力低于对FeHA的亲和力一致。有趣的是，在存在PEMF的情况下，3天和6天后从FeHA释放的DOX量显著增加。PEMF下FeHA释放更高的DOX可以通过超顺磁性FeHA纳米颗粒的机械振动来解释，这种振动打破了与药物的键合并使DOX聚集体从NP表面脱离。体外试验表明，对于所有测试的浓度和时间点，负载在HA和FeHA上的DOX对人骨肉瘤细胞系（SAOS - 2）显示出与游离DOX相同水平的细胞毒性。共聚焦显微镜分析表明，载药纳米颗粒迅速被细胞内化并释放DOX，DOX在细胞核中积累并发挥所需的细胞毒性活性。
