Image-guided surgery using near-infrared Turn-ON fluorescent nanoprobes for precise detection of tumor margins.
Image-guided surgery using near-infrared Turn-ON fluorescent nanoprobes for precise detection of tumor margins.
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DOI：
10.7150/thno.23853
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发表时间：
2018
期刊：
影响因子：
12.4
通讯作者：
Satchi-Fainaro R
中科院分区：
文献类型：
--
作者：
Blau R;Epshtein Y;Pisarevsky E;Tiram G;Israeli Dangoor S;Yeini E;Krivitsky A;Eldar-Boock A;Ben-Shushan D;Gibori H;Scomparin A;Green O;Ben-Nun Y;Merquiol E;Doron H;Blum G;Erez N;Grossman R;Ram Z;Shabat D;Satchi-Fainaro R
手术中肿瘤的完全切除对患者的生存有很大的影响。为此，外科医生应该检测肿瘤，将其切除，并确认没有残留的癌细胞。手术切除组织切口边缘残留的细胞与肿瘤复发和患者预后不良有关。为了在对健康组织造成最小附带损害的情况下完全切除肿瘤组织，需要一种能够区分肿瘤及其正常环境的诊断工具。方法：我们设计、合成并表征了三种新型的聚合on探针，它们将在肿瘤部位被高表达的半胱氨酸组织蛋白酶激活。利用原位乳腺癌和黑色素瘤模型，自发转移到大脑，我们研究了我们的聚合Turn-ON纳米探针的动力学。结果：迄今为止，已经报道了许多低分子量组织蛋白酶敏感底物，然而，它们中的大多数在给药后不久就会被快速清除和信号减弱。在这里，我们展示了通过组织蛋白酶激活我们的Turn-ON探针后肿瘤与背景比的改善。在整个手术过程中，从肿瘤中获得的信号稳定，并划定了肿瘤边界，可以准确切除。结论：我们的研究结果表明，对照组荷瘤小鼠，在白光下进行标准手术或在市售显像剂ProSense®680或5-氨基乙酰丙酸（5-ALA）的荧光引导下，比使用我们的on探针进行图像引导手术（IGS）的组存活时间更短，肿瘤复发更早。我们的“智能”聚合物探针可以帮助外科医生在手术过程中实时决定需要切除的肿瘤边缘，从而改善患者的预后。
Complete tumor removal during surgery has a great impact on patient survival. To that end, the surgeon should detect the tumor, remove it and validate that there are no residual cancer cells left behind. Residual cells at the incision margin of the tissue removed during surgery are associated with tumor recurrence and poor prognosis for the patient. In order to remove the tumor tissue completely with minimal collateral damage to healthy tissue, there is a need for diagnostic tools that will differentiate between the tumor and its normal surroundings. Methods: We designed, synthesized and characterized three novel polymeric Turn-ON probes that will be activated at the tumor site by cysteine cathepsins that are highly expressed in multiple tumor types. Utilizing orthotopic breast cancer and melanoma models, which spontaneously metastasize to the brain, we studied the kinetics of our polymeric Turn-ON nano-probes. Results: To date, numerous low molecular weight cathepsin-sensitive substrates have been reported, however, most of them suffer from rapid clearance and reduced signal shortly after administration. Here, we show an improved tumor-to-background ratio upon activation of our Turn-ON probes by cathepsins. The signal obtained from the tumor was stable and delineated the tumor boundaries during the whole surgical procedure, enabling accurate resection. Conclusions: Our findings show that the control groups of tumor-bearing mice, which underwent either standard surgery under white light only or under the fluorescence guidance of the commercially-available imaging agents ProSense® 680 or 5-aminolevulinic acid (5-ALA), survived for less time and suffered from tumor recurrence earlier than the group that underwent image-guided surgery (IGS) using our Turn-ON probes. Our "smart" polymeric probes can potentially assist surgeons' decision in real-time during surgery regarding the tumor margins needed to be removed, leading to improved patient outcome.
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影响因子：
8.8
作者：
Jones, AS;Hanafi, ZB;Nadapalan, V;Roland, NJ;Kinsella, A;Helliwell, TR
通讯作者：
Helliwell, TR
影响因子：
3.5
作者：
Kanick, Stephen Chad;Davis, Scott C.;Chapman, M. Shane
通讯作者：
Chapman, M. Shane
临床翻译的二氧化硅纳米颗粒作为以癌为标志性的探针进行图像引导的手术和干预措施。
DOI：
10.1039/c2ib20174g
发表时间：
2013-01
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Bradbury MS;Phillips E;Montero PH;Cheal SM;Stambuk H;Durack JC;Sofocleous CT;Meester RJ;Wiesner U;Patel S
通讯作者：
Patel S
影响因子：
14.8
作者：
Blum, Galia;von Degenfeld, Georges;Bogyo, Matthew
通讯作者：
Bogyo, Matthew
DOI：
10.1002/prca.201300105
发表时间：
2014-06
期刊：
Proteomics. Clinical applications
影响因子：
--
作者：
Aggarwal N;Sloane BF
通讯作者：
Sloane BF