College of Science and General Studies , Alfaisal University , P.O. Box 50927, Riyadh 11533 , Saudi Arabia.
Mol Pharm. 2019 Aug 5;16(8):3577-3587. doi: 10.1021/acs.molpharmaceut.9b00433. Epub 2019 Jul 24.
Engineered superparamagnetic iron oxide nanoparticles (SPIONs) have been studied extensively for their localized homogeneous heat generation in breast cancer therapy. However, challenges such as aggregation and inability to produce sub-10 nm SPIONs limit their potential in magnetothermal ablation. We report a facile, efficient, and robust in situ method for the synthesis of SPIONs within a poly(ethylene glycol) (PEG) reactor adsorbed onto reduced graphene oxide nanosheets (rGO) via the microwave hydrothermal route. This promising modality yields crystalline, stable, biocompatible, and superparamagnetic PEGylated SPION-rGO nanocomposites (NCs) with uniform dispersibility. Our findings show that rGO acts as a breeding ground for the spatially distributed nanosites around which the ferrihydrite seeds accumulate to ultimately transform into immobilized SPIONs. PEG, in parallel, acts as a critical confining agent physically trapping the accumulated seeds to prevent their aggregation and create multiple domains on rGO for the synthesis of quantum-sized SPIONs (9 ± 1 nm in diameter). This dual functionality (rGO and PEG) exhibits a pronounced effect on reducing both the aggregation and the sizes of fabricated SPIONs as confirmed by the scanning transmission electron microscopy images, dynamic light scattering analyses, and the specific absorption rates (SARs). Reduced aggregation lowered the toxicity of NCs, where PEGylated SPION-rGO NCs are more biocompatible than PEGylated SPIONs, showing no significant induction of cell apoptosis, mitochondrial membrane injury, or oxidative stress. Significantly less lactate dehydrogenase release and hence less necrosis are observed after 48 h exposure to high doses of PEGylated SPION-rGO NCs compared with PEGylated SPIONs. NCs induce local heat generation with a SAR value of 1760 ± 97 W/g, reaching up to 43 ± 0.3 °C and causing significant MCF-7 breast tumor cell ablation of about 78 ± 10% upon applying an external magnetic field. Collectively, rGO and PEG functionalities have a synergistic effect on improving the synthesis, stability, biocompatibility, and magnetothermal properties of SPIONs.
经过基因改造的超顺磁性氧化铁纳米粒子（SPIONs）因其在乳腺癌治疗中的局部均匀发热而被广泛研究。然而，诸如聚集和无法产生小于 10nm 的 SPIONs 等挑战限制了它们在磁热消融中的潜力。我们报告了一种简便、高效和稳健的原位方法，通过微波水热途径在吸附在还原氧化石墨烯纳米片（rGO）上的聚乙二醇（PEG）反应器中合成 SPIONs。这种有前途的方式产生了结晶、稳定、生物相容和超顺磁性的 PEG 化 SPION-rGO 纳米复合材料（NCs），具有均匀的分散性。我们的研究结果表明，rGO 充当了空间分布纳米位点的滋生地，铁氢氧化物种子在这些纳米位点上积累，最终转化为固定的 SPIONs。同时，PEG 作为一种关键的限制剂，物理地捕获积累的种子，防止它们聚集，并在 rGO 上创建多个域，用于合成量子尺寸的 SPIONs（直径为 9±1nm）。这种双重功能（rGO 和 PEG）对降低聚集和制造的 SPIONs 的尺寸都有明显的影响，这一点从扫描透射电子显微镜图像、动态光散射分析和比吸收率（SAR）得到了证实。减少聚集降低了 NCs 的毒性，其中 PEG 化 SPION-rGO NCs 比 PEG 化 SPIONs 更具生物相容性，没有显著诱导细胞凋亡、线粒体膜损伤或氧化应激。与 PEG 化 SPIONs 相比，在高剂量暴露 48 小时后，PEG 化 SPION-rGO NCs 观察到乳酸脱氢酶释放较少，因此坏死较少。NCs 诱导局部发热，SAR 值为 1760±97W/g，达到 43±0.3°C，并在外磁场作用下导致 MCF-7 乳腺癌细胞消融约 78±10%。总的来说，rGO 和 PEG 的功能对改善 SPIONs 的合成、稳定性、生物相容性和磁热性能具有协同作用。
