Sorbonne Universités, UPMC Univ. Paris 06 , CNRS, UMR 8234, Laboratory PHENIX, 4 place Jussieu, F-75005 Paris, France.
Université Paris Diderot , CNRS, UMR 7057, Laboratory MSC, 75205 Paris cedex 13, France.
ACS Appl Mater Interfaces. 2017 Aug 9;9(31):25775-25788. doi: 10.1021/acsami.7b06553. Epub 2017 Jul 27.
Hybrid nanogels, composed of thermoresponsive polymers and superparamagnetic nanoparticles, are attractive nanocarriers for biomedical applications, being able-as a polymer matrix-to uptake and release high quantities of chemotherapeutic agents and-as magnetic nanoparticles-to be heated when exposed to an alternative magnetic field (AMF), better known as magnetic hyperthermia. Herein, biocompatible, pH-responsive, magnetoresponsive, and thermoresponsive nanogels, based on oligo(ethylene glycol) methyl ether methacrylate monomers and a methacrylic acid comonomer were prepared by conventional precipitation radical copolymerization in water, post-assembled by complexation with iron oxide magnetic nanoparticles (MNPs) of maghemite (γ-FeO), and loaded with an anticancer drug (doxorubicin, DOX), for remotely controlled drug release by a "hot spot", as an athermal magnetic hyperthermia strategy against cancer. These nanogels, denoted MagNanoGels, with a hydrodynamic diameter from 328 to 460 nm, as a function of the MNP content, have a swelling-deswelling behavior at their volume phase temperature transition around 47 °C in a physiological medium (pH 7.5), which is above the human body temperature (37 °C). Applying an alternative magnetic field increases the release of DOX by 2-fold, while no macroscopic heating was recorded. This enhanced drug release is due to a shrinking of the polymer network by local heating, as illustrated by the MagNanoGel size decrease under an AMF. In cancer cells, not only do the DOX-MagNanoGels internalize DOX more efficiently than free DOX, but also DOX intracellular release can be remotely triggered under an AMF, in athermal conditions, thus enhancing DOX cytotoxicity.
杂化纳米凝胶由温敏聚合物和超顺磁性纳米粒子组成，是用于生物医学应用的有吸引力的纳米载体，能够作为聚合物基质来摄取和释放大量的化疗药物，并且作为磁性纳米粒子，在暴露于交变磁场（AMF）时能够被加热，这通常被称为磁热疗。在此，通过在水中进行常规沉淀自由基共聚反应，制备了基于聚乙二醇甲基醚甲基丙烯酸酯单体和甲基丙烯酸共单体的生物相容性、pH 响应性、磁响应性和温敏性纳米凝胶，然后通过与磁铁矿（γ-Fe2O3）的磁性纳米粒子（MNPs）络合进行后组装，并负载抗癌药物（阿霉素，DOX），以通过“热点”进行远程控制药物释放，作为一种非热磁热疗策略来对抗癌症。这些纳米凝胶被标记为 MagNanoGels，其水动力学直径为 328 至 460nm，这取决于 MNP 的含量，在生理介质（pH7.5）中其体积相转变温度附近（约 47°C）具有溶胀-收缩行为，这高于人体温度（37°C）。施加交变磁场会使 DOX 的释放增加 2 倍，而没有记录到宏观加热。这种增强的药物释放是由于聚合物网络的局部加热导致的收缩，如在交变磁场下 MagNanoGel 尺寸减小所说明的那样。在癌细胞中，DOX-MagNanoGels 不仅比游离 DOX 更有效地摄取 DOX，而且在非热条件下可以通过交变磁场远程触发 DOX 的细胞内释放，从而增强 DOX 的细胞毒性。
