Department of Physics, University at Buffalo, Buffalo, New York 14260, USA.
Nanoscale. 2018 Nov 29;10(46):21879-21892. doi: 10.1039/c8nr03869d.
The two major limitations for nanoparticle based magnetic hyperthermia in theranostics are the delivery of a sufficient number of magnetic nanoparticles (MNPs) with high heating power to specific target cells and the residence time of the MNPs at the target location. Ferromagnetic or Ferrimagnetic single domain nanoparticles (F-MNPs), with a permanent magnetic dipole, produce larger magnetic and thermal responses than superparamagnetic nanoparticles (SP-MNPs) but also agglomerate more. MNP agglomeration degrades their heating potential due to dipolar interaction effects and interferes with specific targeting. Additionally, MNPs bound to cells are often endocytosed by the cells or, in vivo, cleared out by the immune system via uptake in macrophages. Here, we present a versatile approach to engineer inorganic-polymeric microdisks, loaded with biomolecules, fluorophores and Fe3O4 F-MNPs that solves both challenges. These microdisks deliver the F-MNPs efficiently, while controlling any undesirable agglomeration and dipolar interaction, while also rendering the F-MNPs endocytosis resistant. We show that these micro-devices are suitable carriers to transport a flat assembly of F-MNPs to the cell membrane unchanged, preserving the magnetic response of the MNPs in any biological environment. The F-MNPs concentration per microdisk and degree of MNP interaction are tunable. We demonstrate that the local heat generated in microdisks is proportional to the surface density of F-MNPs when attached to the cell membrane. The key innovation in the production of these microdisks is the fabrication of a mushroom-shaped photolithographic template that enables easy assembly of the inorganic film, polymeric multilayers, and MNP cargo while permitting highly efficient lift-off of the completed microdisks. During the harvesting of the flat microdisks, the supporting mushroom-shaped templates are sacrificed. These resulting magnetic hybrid microdisks are tunable and efficient devices for magnetothermal actuation and hyperthermia.
基于纳米颗粒的磁热疗在治疗中的两个主要限制是将足够数量的具有高热功率的磁性纳米颗粒 (MNPs) 递送到特定的靶细胞和 MNPs 在靶位的停留时间。具有永久磁偶极子的铁磁或亚铁磁单畴纳米颗粒 (F-MNPs) 比超顺磁纳米颗粒 (SP-MNPs) 产生更大的磁和热响应，但也更容易团聚。MNP 团聚由于偶极相互作用而降低其加热潜力，并干扰特定的靶向。此外，与细胞结合的 MNPs 通常被细胞内吞，或者在体内通过巨噬细胞摄取被免疫系统清除。在这里，我们提出了一种通用的方法来设计负载生物分子、荧光团和 Fe3O4 F-MNPs 的无机-聚合物微盘，以解决这两个挑战。这些微盘有效地传递 F-MNPs，同时控制任何不必要的团聚和偶极相互作用，同时使 F-MNPs 抵抗内吞作用。我们表明，这些微器件是将平面组装的 F-MNPs 有效地运送到细胞膜不变的合适载体，在任何生物环境中都能保持 MNPs 的磁响应。每个微盘的 F-MNPs 浓度和 MNP 相互作用程度是可调的。我们证明，当 F-MNPs 附着在细胞膜上时，微盘中产生的局部热量与 F-MNPs 的表面密度成正比。这些微盘的生产中的关键创新是制造蘑菇形光刻模板，该模板允许无机膜、聚合物多层和 MNP 有效组装货物，同时允许高效地脱模完成的微盘。在收集平面微盘时，牺牲支撑蘑菇形模板。这些得到的磁性混合微盘是用于磁热驱动和热疗的可调谐和高效的装置。
