CXCR-4 Targeted, Short Wave Infrared (SWIR) Emitting Nanoprobes for Enhanced Deep Tissue Imaging and Micrometastatic Cancer Lesion Detection.
CXCR-4 Targeted, Short Wave Infrared (SWIR) Emitting Nanoprobes for Enhanced Deep Tissue Imaging and Micrometastatic Cancer Lesion Detection.
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DOI：
10.1002/smll.201502202
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发表时间：
2015-12-16
期刊：
影响因子：
--
通讯作者：
Moghe PV
中科院分区：
文献类型：
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作者：
Zevon M;Ganapathy V;Kantamneni H;Mingozzi M;Kim P;Adler D;Sheng Y;Tan MC;Pierce M;Riman RE;Roth CM;Moghe PV
实现精准医学在癌症治疗中的承诺取决于识别和跟踪癌症的生长，以最大限度地提高治疗方案和改善患者的结果。然而，目前的临床成像技术由于其体积小和亚器官定位而无法检测病变，因此无法实现早期检测的目标。通过适当的探针，光学成像技术可以通过在宏观和微观尺度上识别肿瘤的分子表型来克服这一限制。在这项研究中，我们首次提出使用纳米光子短波红外技术对小的表面下病变进行分子表型分析，以更灵敏地检测和改善患者的预后。为此，我们设计了带配体的人血清白蛋白包封稀土纳米颗粒（ReANCs）用于靶向病变成像。AMD3100是一种CXCR4（一种参与细胞运动的趋化因子受体，是癌症转移的经典标志物）的拮抗剂，被吸附在ReANCs上形成功能化的ReANCs （fReANCs）。当在皮下肿瘤模型中腹腔注射时，功能化纳米颗粒能够区分并优先积聚在受体阳性病变中。此外，在乳腺癌肺转移模型中，静脉给药的fReANCs能够靶向亚组织肿瘤微病变，最大深度为10.5 mm。与未功能化的ReANCs相比，使用fReANCs检测到的内部病变小2.25倍（p < 0.01），最小的肿瘤为18.9 mm3。因此，我们提出了一个集成的纳米探针检测平台，允许亚组织癌病变的靶向特异性鉴定。
Realizing the promise of precision medicine in cancer therapy depends on identifying and tracking of cancerous growths in order to maximize treatment options and improve patient outcomes. However, this goal of early detection remains unfulfilled by current clinical imaging techniques that fail to detect diseased lesions, due to their small size and sub-organ localization. With proper probes, optical imaging techniques can overcome this limitation by identifying the molecular phenotype of tumors at both macroscopic and microscopic scales. In this study, we propose the first use of nanophotonic short wave infrared technology to molecularly phenotype small sub-surface lesions for more sensitive detection and improved patient outcomes. To this end, we designed human serum albumin encapsulated rare-earth (RE) nanoparticles (ReANCs) with ligands for targeted lesion imaging. AMD3100, an antagonist to CXCR4 (a chemokine receptor involved in cell motility and a classic marker of cancer metastasis) was adsorbed onto ReANCs to form functionalized ReANCs (fReANCs). Functionalized nanoparticles were able to discriminate and preferentially accumulate in receptor positive lesions when injected intraperitoneally in a subcutaneous tumor model. Additionally, fReANCs, administered intravenously, were able to target sub-tissue tumor micro-lesions, at a maximum depth of 10.5 mm, in a lung metastatic model of breast cancer. Internal lesions identified with fReANCs were 2.25 times smaller than those detected with unfunctionalized ReANCs (p < .01) with the smallest tumor being 18.9 mm3. Thus, we present an integrated nanoprobe detection platform that allows target-specific identification of sub-tissue cancerous lesions.