首页> 外文会议>Nanobiophotonics and Biomedical Applications III; Progress in Biomedical Optics and Imaging; vol.7, no.18 >Tissue distribution and real-time fluorescence measurement of a tumor-targeted nanodevice by a two photon optical fiber fluorescence probe
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Tissue distribution and real-time fluorescence measurement of a tumor-targeted nanodevice by a two photon optical fiber fluorescence probe

机译:两光子光纤荧光探针对靶向肿瘤的纳米器件的组织分布和实时荧光测量

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Real-time fluorescence measurement in deep tumors in live animals (or humans) by conventional methods has significant challenges. We have developed a two-photon optical fiber fluorescence (TPOFF) probe as a minimally invasive technique for quantifying fluorescence in solid tumors in live mice. Here we demonstrate TPOFF for real-time measurements of targeted drug delivery dynamics to tumors in live mice. 50-femtosecond laser pulses at 800 nm were coupled into a single mode optical fiber and delivered into the tumor through a 27-gauge needle. Fluorescence was collected back through the same fiber, filtered, and detected with photon counting. Biocompatible dendrimer-based nanoparticles were used for targeted delivery of fluorescent materials into tumors. Dendrimers with targeting agent folic acid and fluorescent reporter 6-TAMRA (G5-6T-FA) were synthesized. KB cell tumors expressing high levels of FA receptors were developed in SCID mice. We initially demonstrated the specific uptake of the targeted conjugates into tumor, kidney and liver, using the TPOFF probe. The tumor fluorescence was then taken in live mice at 30 min, 2 h and 24 h with the TPOFF probe. G5-6T-FA accumulated in the tumor with maximum mean levels reaching 673 ± 67 nM at the 2 h time point. In contrast, the levels of a control, non-targeted conjugate (G5-6T) at 2 h reached a level of only 136 ± 28 nM in tumors, and decrease quickly. This indicates that the TPOFF probe can be used as a minimally invasive detection system for quantifying the specific targeting of a fluorescent nanodevice on a real-time basis.
机译:通过常规方法对活体动物(或人类)的深部肿瘤进行实时荧光测量具有重大挑战。我们已经开发出一种双光子光纤荧光(TPOFF)探针,作为一种定量检测活小鼠实体瘤中荧光的微创技术。在这里,我们演示了TPOFF用于实时测量活小鼠肿瘤靶向药物递送动力学的方法。在800 nm处的50飞秒激光脉冲被耦合到单模光纤中,并通过27号针头传递到肿瘤中。通过同一根光纤收​​集荧光,过滤并通过光子计数进行检测。基于生物相容性树枝状聚合物的纳米颗粒用于将荧光物质靶向递送到肿瘤中。合成了具有靶向剂叶酸和荧光报告基因6-TAMRA(G5-6T-FA)的树状聚合物。在SCID小鼠中发展了表达高水平FA受体的KB细胞肿瘤。我们最初使用TPOFF探针证明了靶向缀合物对肿瘤,肾脏和肝脏的特异性摄取。然后在30分钟,2小时和24小时用TPOFF探针在活小鼠中采集肿瘤荧光。 G5-6T-FA在肿瘤中蓄积,在2 h时间点的最大平均水平达到673±67 nM。相反,在肿瘤中2 h的对照,非靶向结合物(G5-6T)的水平仅达到136±28 nM,并迅速下降。这表明TPOFF探针可以用作微创检测系统,用于实时定量荧光纳米器件的特异性靶向。

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