Despite being one of the most common cancers, bladder cancer is largely inefficiently and inaccurately staged and monitored. Current imaging methods detect cancer only when it has reached “visible” size and has significantly disrupted the structure of the organ. By that time, thousands of cells will have proliferated and perhaps metastasized. Repeated biopsies and scans are necessary to determine the effect of therapy on cancer growth. In this report, we describe a novel approach based on multimodal nanoparticle contrast agent technology and its application to a preclinical animal model of bladder cancer. The innovation relies on the engineering core of mesoporous silica with specific scanning contrast properties and surface modification that include fluorescence and magnetic resonance imaging (MRI) contrast. The overall dimensions of the nano-device are preset at 80–180 nm, depending on composition with a pore size of 2 nm. To facilitate and expedite discoveries, we combined a well-known model of bladder cancer and our novel technology. We exposed nanoparticles to MB49 murine bladder cancer cells in vitro and found that 70 % of the cells were labeled by nanoparticles as measured by flow cytometry. The in vivo mouse model for bladder cancer is particularly well suited for T1- and T2-weighted MRI. Under our experimental conditions, we demonstrate that the nanoparticles considerably improve tumor definition in terms of volumetric, intensity and structural characteristics. Important bladder tumor parameters can be ascertained, non-invasively, repetitively, and with great accuracy. Furthermore, since the particles are not biodegradable, repetitive injection is not required. This feature allows follow-up diagnostic evaluations during cancer treatment. Changes in MRI signals show that in situ uptake of free particles has predilection to tumor cells relative to normal bladder epithelium. The particle distribution within the tumors was corroborated by fluorescent microscopy of sections of excised bladders. In addition, MRI imaging revealed fibrous finger-like projections into the tumors where particles insinuated themselves deeply. This morphological characteristic was confirmed by fluorescence microscopy. These findings may present new options for therapeutic intervention. Ultimately, the combination of real-time and repeated MRI evaluation of the tumors enhanced by nanoparticle contrast may have the potential for translation into human clinical studies for tumor staging, therapeutic monitoring, and drug delivery.

中文翻译：

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纳米技术与癌症：利用多峰介孔二氧化硅纳米粒子改善膀胱癌的实时监测和分期。

尽管是最常见的癌症之一，但膀胱癌的效率低下，分期和监测不准确。当前的成像方法仅在达到“可见”大小并显着破坏器官结构时才能检测到癌症。到那时，成千上万的细胞已经增殖并且可能已经转移。重复活检和扫描对于确定治疗对癌症生长的影响是必要的。在本报告中，我们描述了一种基于多峰纳米粒子造影剂技术的新方法及其在膀胱癌临床前动物模型中的应用。该创新依靠具有特殊扫描对比度特性和表面修饰（包括荧光和磁共振成像（MRI）对比度）的介孔二氧化硅的工程核心。纳米装置的整体尺寸预设为80-180 nm，具体取决于孔径为2 nm的成分。为了促进和加快发现，我们将著名的膀胱癌模型与我们的新技术相结合。我们在体外将纳米颗粒暴露于MB49鼠膀胱癌细胞中，发现流式细胞仪检测到70％的细胞被纳米颗粒标记。膀胱癌的体内小鼠模型特别适合于T1和T2加权MRI。在我们的实验条件下，我们证明纳米颗粒在体积，强度和结构特征方面大大改善了肿瘤的定义。重要的膀胱肿瘤参数可以非侵入性，重复性和高精度地确定。此外，由于颗粒不可生物降解，不需要重复注射。此功能允许在癌症治疗期间进行后续诊断评估。MRI信号的变化表明，相对于正常膀胱上皮，游离颗粒的原位摄取倾向于肿瘤细胞。通过切除的膀胱切片的荧光显微镜检查证实了肿瘤内的颗粒分布。此外，MRI成像显示出纤维状的手指状突起进入肿瘤，其中颗粒深深地暗示了自身。该形态特征通过荧光显微镜确认。这些发现可能为治疗干预提供新的选择。最终，通过纳米粒子对比增强的实时和重复MRI评估肿瘤的组合可能具有转化为人类临床研究进行肿瘤分期的潜力，