ACS Nano. 2019 Feb 26;13(2):1292-1308. doi: 10.1021/acsnano.8b06655. Epub 2019 Jan 18.
Noninvasive stimuli-responsive drug delivery using magnetic fields in conjunction with superparamagnetic nanoparticles offers the potential for the spatial and temporal control of drug release. When hyperthermia is not desired and control of the dosage is required, it is necessary to design a platform in which local heating on the nanoscale releases the therapeutic cargo without the bulk heating of the surrounding medium. In this paper, we report a design using a stimuli-responsive nanoparticle platform to control the dosage of the cargo released by an alternating magnetic field (AMF) actuation. A core@shell structure with a superparamagnetic doped iron oxide (MnFeO@CoFeO) nanoparticle core in a mesoporous silica shell was synthesized. The core used here has a high saturation magnetization value and a high specific loss power for heat generation under an AMF. The mesoporous shell has a high cargo-carrying capacity. A thermoresponsive molecular-based gatekeeper containing an aliphatic azo group was modified on the core@shell nanoparticles to regulate the cargo release. The mesoporous structure of the silica shell remained intact after exposure to an AMF, showing that the release of cargo is due to the removal of the gatekeepers instead of the destruction of the structure. Most importantly, we demonstrated that the amount of cargo released could be adjusted by the AMF exposure time. By applying multiple sequential exposures of AMF, we were able to release the cargo step-wise and increase the total amount of released cargo. In vitro studies showed that the death of pancreatic cancer cells treated by drug-loaded nanoparticles was controlled by different lengths of AMF exposure time due to different amount of drugs released from the carriers. The strategy developed here holds great promise for achieving the dosage, temporal, and spatial control of therapeutics delivery without the risk of overheating the particles' surroundings.
使用磁场与超顺磁纳米粒子结合的非侵入性刺激响应药物输送为药物释放的时空控制提供了潜力。当不需要热疗并且需要控制剂量时,有必要设计一个平台,在该平台上,纳米级别的局部加热可以释放治疗货物,而不会对周围介质进行整体加热。在本文中,我们报告了一种使用刺激响应纳米粒子平台来控制货物释放剂量的设计,该设计通过交变磁场(AMF)致动来实现。合成了一种具有超顺磁性掺杂氧化铁(MnFeO@CoFeO)纳米核的介孔硅壳的核壳结构。这里使用的核具有高饱和磁化强度值和在 AMF 下产生热量的高热损耗功率。介孔壳具有高载物能力。在核壳纳米粒子上修饰了含有脂肪族偶氮基团的热响应分子型门控剂,以调节货物的释放。介孔硅壳的介孔结构在暴露于 AMF 后保持完整,表明货物的释放是由于门控剂的去除而不是结构的破坏。最重要的是,我们证明了通过 AMF 暴露时间可以调节货物的释放量。通过施加多个顺序的 AMF 暴露,可以逐步释放货物并增加释放的货物总量。体外研究表明,由于载体释放的药物量不同,经载药纳米粒子处理的胰腺癌细胞的死亡受到不同 AMF 暴露时间的控制。这里开发的策略有望实现治疗药物输送的剂量、时间和空间控制,而不会有颗粒周围过热的风险。
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