Zevon Margot, Ganapathy Vidya, Kantamneni Harini, Mingozzi Marco, Kim Paul, Adler Derek, Sheng Yang, Tan Mei Chee, Pierce Mark, Riman Richard E, Roth Charles M, Moghe Prabhas V
Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ, 08854, USA.
Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, 08854, USA.
Small. 2015 Dec 16;11(47):6347-57. doi: 10.1002/smll.201502202. Epub 2015 Oct 30.
Realizing the promise of precision medicine in cancer therapy depends on identifying and tracking cancerous growths to maximize treatment options and improve patient outcomes. This goal of early detection remains unfulfilled by current clinical imaging techniques that fail to detect lesions due to their small size and suborgan localization. With proper probes, optical imaging techniques can overcome this by identifying the molecular phenotype of tumors at both macroscopic and microscopic scales. In this study, the first use of nanophotonic short wave infrared technology is proposed to molecularly phenotype small lesions for more sensitive detection. Here, human serum albumin encapsulated rare-earth nanoparticles (ReANCs) with ligands for targeted lesion imaging are designed. AMD3100, an antagonist to CXCR4 (a classic marker of cancer metastasis) is adsorbed onto ReANCs to form functionalized ReANCs (fReANCs). fReANCs are able to preferentially accumulate in receptor positive lesions when injected intraperitoneally in a subcutaneous tumor model. fReANCs can also target subtissue microlesions at a maximum depth of 10.5 mm in a lung metastatic model of breast cancer. Internal lesions identified with fReANCs are 2.25 times smaller than those detected with ReANCs. Thus, an integrated nanoprobe detection platform is presented, which allows target-specific identification of subtissue cancerous lesions.
实现精准医学在癌症治疗中的前景取决于识别和追踪癌性生长,以最大化治疗选择并改善患者预后。早期检测的这一目标尚未被当前的临床成像技术实现,这些技术因病变尺寸小和位于亚器官位置而无法检测到病变。借助合适的探针,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问题。在本研究中,提出首次使用纳米光子短波红外技术对小病变进行分子表型分析以实现更灵敏的检测。在此,设计了包裹有人血清白蛋白的稀土纳米颗粒(ReANCs)并带有用于靶向病变成像的配体。AMD3100,一种CXCR4(癌症转移的经典标志物)拮抗剂,被吸附到ReANCs上以形成功能化的ReANCs(fReANCs)。在皮下肿瘤模型中腹腔注射时,fReANCs能够优先在受体阳性病变中积累。在乳腺癌肺转移模型中,fReANCs还能够靶向最大深度为10.5毫米的亚组织微病变。用fReANCs识别出的内部病变比用ReANCs检测到的病变小2.25倍。因此,提出了一种集成纳米探针检测平台,其能够对亚组织癌性病变进行靶向特异性识别。