Highly Specific and Sensitive Fluorescent Nanoprobes for Image-Guided Resection of Sub-Millimeter Peritoneal Tumors.
Highly Specific and Sensitive Fluorescent Nanoprobes for Image-Guided Resection of Sub-Millimeter Peritoneal Tumors.
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DOI：
10.1021/acsnano.6b06777
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发表时间：
2017-02-28
期刊：
影响因子：
17.1
通讯作者：
Herrera VL
中科院分区：
文献类型：
--
作者：
Colby AH;Berry SM;Moran AM;Pasion KA;Liu R;Colson YL;Ruiz-Opazo N;Grinstaff MW;Herrera VL
目前腹膜转移癌的治疗面临的挑战是不能检测、可视化和切除胰腺、卵巢或间皮起源的小肿瘤或显微镜下肿瘤。在这些疾病中，原发性肿瘤切除的完整性与患者存活率直接相关，因此，识别小的亚毫米肿瘤（即，传播性疾病）至关重要。因此，需要新的成像技术和探针来改善细胞减灭术和患者结果。描述了高度荧光罗丹明标记的可膨胀纳米颗粒（HFR-eNPs）在胰腺癌转移的细胞减灭术期间用作视觉辅助。与游离罗丹明相比，罗丹明共价掺入~30 nm eNP中增加了荧光信号，从而提供了比单个罗丹明分子更亮和更有效的探针。使用腹膜内给药途径，HFR-eNPs定位于三种不同动物模型中的大（~ 1cm）、亚厘米和亚毫米腹膜内肿瘤的区域，包括胰腺癌、间皮瘤和卵巢癌。HFR-eNPs的肿瘤定位取决于材料性质（即，eNP聚合物）以及表面化学（阴离子表面活性剂与PEG化的不带电表面活性剂）。在胰腺癌病的大鼠模型中，针对金标准组织病理学分析验证了肿瘤的HFR-eNP鉴定，以揭示HFR-eNP对肿瘤具有高特异性（99%）和灵敏度（92%），特别是亚厘米和微观亚毫米肿瘤，总体准确度为95%。最后，作为概念验证，HFR-eNPs用于指导腹膜癌病大鼠模型中胰腺肿瘤的切除。
A current challenge in the treatment of peritoneal carcinomatosis is the inability to detect, visualize, and resect small or microscopic tumors of pancreatic, ovarian, or mesothelial origin. In these diseases, the completeness of primary tumor resection is directly correlated with patient survival, and hence, identifying small sub-millimeter tumors (i.e., disseminated disease) is critical. Thus, new imaging techniques and probes are needed to improve cytoreductive surgery and patient outcomes. Highly fluorescent rhodamine-labeled expansile nanoparticles (HFR-eNPs) are described for use as a visual aid during cytoreductive surgery of pancreatic carcinomatosis. The covalent incorporation of rhodamine into ~30 nm eNPs increases the fluorescent signal compared to free rhodamine, thereby affording a brighter and more effective probe than would be achieved by a single rhodamine molecule. Using the intraperitoneal route of administration, HFR-eNPs localize to regions of large (~1 cm), sub-centimeter, and sub-millimeter intraperitoneal tumor in three different animal models, including pancreatic, mesothelioma, and ovarian carcinoma. Tumoral localization of the HFR-eNPs depends on both the material property (i.e., eNP polymer) as well as the surface chemistry (anionic surfactant vs PEGylated noncharged surfactant). In a rat model of pancreatic carcinomatosis, HFR-eNP identification of tumor is validated against gold-standard histopathological analysis to reveal that HFR-eNPs possess high specificity (99%) and sensitivity (92%) for tumors, in particular, sub-centimeter and microscopic sub-millimeter tumors, with an overall accuracy of 95%. Finally, as a proof-of-concept, HFR-eNPs are used to guide the resection of pancreatic tumors in a rat model of peritoneal carcinomatosis.
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影响因子：
14
作者：
Liu, Rong;Gilmore, Denis M.;Zubris, Kimberly Ann V.;Xu, Xiaoyin;Catalano, Paul J.;Padera, Robert F.;Grinstaff, Mark W.;Colson, Yolonda L.
通讯作者：
Colson, Yolonda L.
影响因子：
4.7
作者：
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Mohs, Aaron M.
影响因子：
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作者：
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通讯作者：
Grinstaff MW
影响因子：
3.7
作者：
Gilmore, Denis M.;Khullar, Onkar V.;Russell, Sara E.
通讯作者：
Russell, Sara E.
影响因子：
14
作者：
Liu R;Colby AH;Gilmore D;Schulz M;Zeng J;Padera RF;Shirihai O;Grinstaff MW;Colson YL
通讯作者：
Colson YL