Wallat Jaqueline D, Czapar Anna E, Wang Charlie, Wen Amy M, Wek Kristen S, Yu Xin, Steinmetz Nicole F, Pokorski Jonathan K
Department of Macromolecular Science and Engineering, Case Western Reserve University, Case School of Engineering , Cleveland, Ohio 44106, United States.
Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, Ohio 44106, United States.
Biomacromolecules. 2017 Jan 9;18(1):103-112. doi: 10.1021/acs.biomac.6b01389. Epub 2016 Dec 19.
Improved imaging of cancerous tissue has the potential to aid prognosis and improve patient outcome through longitudinal imaging of treatment response and disease progression. While nuclear imaging has made headway in cancer imaging, fluorinated tracers that enable magnetic resonance imaging (F MRI) hold promise, particularly for repeated imaging sessions because nonionizing radiation is used. Fluorine MRI detects molecular signatures by imaging a fluorinated tracer and takes advantage of the spatial and anatomical resolution afforded by MRI. This manuscript describes a fluorous polymeric nanoparticle that is capable of F MR imaging and fluorescent tracking for in vitro and in vivo monitoring of immune cells and cancerous tissue. The fluorous particle is derived from low-molecular-weight amphiphilic copolymers that self-assemble into micelles with a hydrodynamic diameter of 260 nm. The polymer is MR-active at concentrations as low as 2.1 mM in phantom imaging studies. The fluorinated particle demonstrated rapid uptake into immune cells for potential cell-tracking or delineation of the tumor microenvironment and showed negligible toxicity. Systemic administration indicates significant uptake into two tumor types, triple-negative breast cancer and ovarian cancer, with little accumulation in off-target tissue. These results indicate a robust platform imaging agent capable of immune cell tracking and systemic disease monitoring with exceptional uptake of the nanoparticle in multiple cancer models.
改进的癌组织成像技术有潜力通过对治疗反应和疾病进展进行纵向成像来辅助预后评估并改善患者治疗效果。虽然核成像在癌症成像方面已取得进展,但能够实现磁共振成像(F MRI)的氟化示踪剂很有前景,特别是对于重复成像检查,因为其使用的是非电离辐射。氟磁共振成像通过对氟化示踪剂成像来检测分子特征,并利用磁共振成像所提供的空间和解剖分辨率。本手稿描述了一种含氟聚合物纳米颗粒,它能够进行F MR成像和荧光追踪,用于体外和体内免疫细胞及癌组织的监测。这种含氟颗粒由低分子量两亲共聚物衍生而来,这些共聚物自组装成流体动力学直径为260 nm的胶束。在体模成像研究中,该聚合物在低至2.1 mM的浓度下就具有磁共振活性。这种氟化颗粒显示出能快速被免疫细胞摄取,可用于潜在的细胞追踪或肿瘤微环境的描绘,并且毒性可忽略不计。全身给药表明,它能大量摄取到三阴性乳腺癌和卵巢癌这两种肿瘤类型中,而在非靶组织中的积累很少。这些结果表明,该纳米颗粒是一种强大的平台成像剂,能够在多种癌症模型中对免疫细胞进行追踪并对全身性疾病进行监测,且纳米颗粒摄取效果极佳。