Department of Chemistry, University of Massachusetts Lowell, Lowell, MA 01854, USA.
Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
Int J Mol Sci. 2022 Sep 1;23(17):9926. doi: 10.3390/ijms23179926.
For many cancer types, being undetectable from early symptoms or blood tests, or often detected at late stages, medical imaging emerges as the most efficient tool for cancer screening. MRI, ultrasound, X-rays (mammography), and X-ray CT (CT) are currently used in hospitals with variable costs. Diagnostic materials that can detect breast tumors through molecular recognition and amplify the signal at the targeting site in combination with state-of-the-art CT techniques, such as dual-energy CT, could lead to a more precise detection and assist significantly in image-guided intervention. Herein, we have developed a ligand-specific X-ray contrast agent that recognizes α5β1 integrins overexpressed in MDA-MB-231 breast cancer cells for detection of triple (-) cancer, which proliferates very aggressively. In vitro studies show binding and internalization of our nanoprobes within those cells, towards uncoated nanoparticles (NPs) and saline. In vivo studies show high retention of ~3 nm ligand-PEG-S-AuNPs in breast tumors in mice (up to 21 days) and pronounced CT detection, with statistical significance from saline and iohexol, though only 0.5 mg of metal were utilized. In addition, accumulation of ligand-specific NPs is shown in tumors with minimal presence in other organs, relative to controls. The prolonged, low-metal, NP-enhanced spectral-CT detection of triple (-) breast cancer could lead to breakthrough advances in X-ray cancer diagnostics, nanotechnology, and medicine.
对于许多癌症类型，早期症状或血液检测无法检测到，或者经常在晚期检测到，医学成像成为癌症筛查最有效的工具。磁共振成像（MRI）、超声、X 射线（乳房 X 光检查）和 X 射线计算机断层扫描（CT）目前在医院中使用，成本不同。能够通过分子识别检测乳腺癌肿瘤并与最先进的 CT 技术（如双能 CT）相结合在靶向部位放大信号的诊断材料，可以实现更精确的检测，并大大有助于图像引导干预。在此，我们开发了一种配体特异性 X 射线造影剂，用于识别 MDA-MB-231 乳腺癌细胞中过度表达的 α5β1 整合素，以检测三重（-）癌症，该癌症的增殖非常活跃。体外研究表明，我们的纳米探针在这些细胞内结合和内化，对未涂层的纳米颗粒（NPs）和盐水也是如此。体内研究表明，在小鼠的乳腺癌中，~3nm 配体-PEG-S-AuNPs 的保留率很高（高达 21 天），并且 CT 检测明显，与盐水和碘海醇相比具有统计学意义，尽管仅使用了 0.5mg 的金属。此外，与对照相比，配体特异性 NPs 在肿瘤中的积累很少，而在其他器官中存在。三重（-）乳腺癌的长时、低金属、NP 增强光谱 CT 检测可能会在 X 射线癌症诊断、纳米技术和医学方面取得突破性进展。
