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PEG-mediated synthesis of highly dispersive multifunctional superparamagnetic nanoparticles: Their physicochemical properties and function in vivo

机译:PEG介导的高度分散的多功能超顺磁性纳米粒子的合成:其理化性质和体内功能

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摘要

Multifunctional superparamagnetic nanoparticles have been developed for a wide range of applications in nanomedicine, such as serving as tumor-targeted drug carriers and molecular imaging agents. To function in vivo, the development of these novel materials must overcome several challenging requirements including biocompatibility, stability in physiological solutions, nontoxicity, and the ability to traverse biological barriers. Here we report a PEG-mediated synthesis process to produce well-dispersed, ultrafine, and highly stable iron oxide nanoparticles for in vivo applications. Utilizing a biocompatible PEG coating bearing amine functional groups, the produced nanoparticles serve as an effective platform with the ability to incorporate a variety of targeting, therapeutic, or imaging ligands. In this study, we demonstrated tumor-specific accumulation of these nanoparticles through both magnetic resonance and optical imaging after conjugation with chlorotoxin, a peptide with high affinity toward tumors of the neuroectodermal origin, and Cy5.5, a near-infrared fluorescent dye. Furthermore, we performed preliminary biodistribution and toxicity assessments of these nanoparticles in wild-type mice through histological analysis of clearance organs and hematology assay, and the results demonstrated the relative biocompatibility of these nanoparticles.
机译:多功能超顺磁性纳米颗粒已被开发用于纳米医学中的广泛应用,例如用作靶向肿瘤的药物载体和分子成像剂。为了在体内发挥作用,这些新型材料的开发必须克服几个具有挑战性的要求,包括生物相容性,在生理溶液中的稳定性,无毒性和穿越生物屏障的能力。在这里,我们报告了P​​EG介导的合成过程,以产生分散良好,超细且高度稳定的氧化铁纳米颗粒,用于体内应用。利用带有胺官能团的生物相容性PEG涂层,产生的纳米颗粒可作为有效平台,并具有结合多种靶向,治疗或成像配体的能力。在这项研究中,我们证明了在与氯毒素(一种对神经外胚层起源的肿瘤具有高亲和力的肽)和Cy5.5(一种近红外荧光染料)结合后,通过磁共振和光学成像,这些纳米颗粒在肿瘤中的特异性聚集。此外,我们通过清除器官的组织学分析和血液学测定对野生型小鼠中的这些纳米颗粒进行了初步的生物分布和毒性评估,结果证明了这些纳米颗粒的相对生物相容性。

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