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Surface-Enhanced Raman Scattering Nanoparticles for Multiplexed Imaging of Bladder Cancer Tissue Permeability and Molecular Phenotype.
ACS Nano ( IF 15.8 ) Pub Date : 2018-09-11 , DOI: 10.1021/acsnano.8b03217
Ryan M Davis , Bernhard Kiss 1 , Dharati R Trivedi 1, 2 , Thomas J Metzner 1 , Joseph C Liao 1, 2 , Sanjiv S Gambhir
Affiliation  

Bladder cancer has the highest recurrence rate of all cancers due in part to inadequate transurethral resection. Inadequate resection is caused by the inability of cystoscopes to detect invisible lesions during the resection procedure. To improve detection and resection of nonmuscle invasive bladder cancer, we quantified the ability of a surface-enhanced Raman nanoparticle and endoscope system to classify bladder tissue as normal or cancerous. Both antibody-based (active) and tissue permeability-based (passive) targeting mechanisms were evaluated by topically applying nanoparticles to ex vivo human bladder tissue samples. Multiplexed molecular imaging of CD47 and Carbonic Anhydrase 9 tumor proteins gave a receiver operating characteristic area under the curve (ROC AUC of 0.93 (0.75, 1.00). Furthermore, passively targeted nanoparticles enabled tissue classification with an ROC AUC of 0.93 (0.73, 1.00). Passively targeted nanoparticles penetrated 5-fold deeper and bound to tumor tissue at 3.3-fold higher concentrations in cancer compared to normal bladder urothelium, suggesting the existence of an enhanced surface permeability and retention effect in human bladder cancer.

中文翻译:

表面增强拉曼散射纳米粒子对膀胱癌组织渗透性和分子表型的多重成像。

膀胱癌在所有癌症中的复发率最高,部分原因是经尿道切除术不充分。切除不充分是由于膀胱镜在切除过程中无法检测到看不见的病变所致。为了改善非肌肉浸润性膀胱癌的检测和切除,我们量化了表面增强拉曼纳米颗粒和内窥镜系统将膀胱组织分类为正常或癌性的能力。通过将纳米颗粒局部应用于离体人膀胱组织样品,评估了基于抗体(主动)和基于组织渗透性(被动)的靶向机制。CD47和碳酸酐酶9肿瘤蛋白的多重分子成像显示了曲线下的受体工作特征区域(ROC AUC为0.93(0.75,1.00)。被动靶向纳米粒子能够实现组织分类,ROC AUC为0.93(0.73,1.00)。与正常膀胱尿路上皮相比,被动靶向的纳米粒子在癌症中的渗透深度更深5倍,并以3.3倍的较高浓度与肿瘤组织结合,这表明在人类膀胱癌中存在增强的表面通透性和保留作用。
更新日期:2018-09-11
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