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Developing hyperpolarized silicon particles for advanced biomedical imaging applications

机译:开发用于高级生物医学成像应用的超极化硅颗粒

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Silicon-based nanoparticles are ideally suited as biomedical imaging agents, due to their biocompatibility, biodegradability, and simple surface chemistry that is amenable to drug loading and targeting. A method of hyperpolarizing silicon particles using dynamic nuclear polarization (DNP), which increases magnetic resonance imaging (MRI) signals by 4-5 orders of magnitude through enhanced nuclear spin alignment, has recently been developed and shown viable as a contrast agent for in vivo MRI. Naturally occurring electronic defects on the particle surface obviate the need for exogenous radicals, and the enhanced spin polarization lasts for significantly longer than other hyperpolarized agents (tens of minutes, instead of <1 minute for other species). We report our recent advances in determining the MR characteristics of hyperpolarized silicon particles, which could lead to non-invasive, non-radioactive molecular targeted imaging of various cancer systems. A variety of particle sizes (20 nm-2 μm) were found to have hyperpolarized relaxation times ranging from ~10-50 minutes. The addition of various functional groups to the particle surface, including biocompatible polymers, aptamers, and antibodies had no effect to the hyperpolarization dynamics or relaxation times, and appear to satisfactorily survive the harsh temperature conditions of DNP. Preliminary in vivo studies examined a variety of particle administration routes in mice, including intraperitoneal, tail vein, and rectal injections, as well as oral gavage. Ongoing experiments include targeted molecular imaging in orthotopic murine models of ovarian and colorectal cancers.
机译:基于硅的纳米颗粒由于其生物相容性,生物降解性以及适合药物装载和靶向的简单表面化学性质,因此非常适合用作生物医学成像剂。最近开发了一种使用动态核极化(DNP)来超极化硅颗粒的方法,该方法通过增强的核自旋对准将磁共振成像(MRI)信号增加4-5个数量级,并且已显示出可作为体内造影剂的可行性核磁共振成像。粒子表面上自然发生的电子缺陷消除了对外源自由基的需要,增强的自旋极化比其他超极化剂的持续时间长得多(数十分钟,而不是其他物种的<1分钟)。我们报告了我们在确定超极化硅颗粒的MR特性方面的最新进展,这可能导致各种癌症系统的非侵入性,非放射性分子靶向成像。发现各种粒径(20 nm-2μm)的超极化弛豫时间约为10-50分钟。向颗粒表面添加各种功能基团,包括生物相容性聚合物,适体和抗体,对超极化动力学或弛豫时间没有影响,并且似乎可以令人满意地在DNP的苛刻温度条件下生存。初步的体内研究检查了小鼠的各种颗粒给药途径,包括腹膜内,尾静脉和直肠注射以及管饲法。正在进行的实验包括在卵巢癌和大肠癌的原位鼠模型中进行靶向分子成像。

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