Department of Urology, Yale University, New Haven, CT.
Department of Biomedical Engineering, Yale University, New Haven, CT.
Nanomedicine. 2022 Feb;40:102477. doi: 10.1016/j.nano.2021.102477. Epub 2021 Nov 3.
Magnetic resonance is a key imaging tool for the detection of prostate cancer; however, better tools focusing on cancer specificity are required to distinguish benign from cancerous regions. We found higher expression of claudin-3 (CLDN-3) and -4 (CLDN-4) in higher grade than lower-grade human prostate cancer biopsies (n = 174), leading to the design of functionalized nanoparticles (NPs) with a non-toxic truncated version of the natural ligand Clostridium perfringens enterotoxin (C-CPE) that has a strong binding affinity to Cldn-3 and Cldn-4 receptors. We developed a first-of-its-type, C-CPE-NP-based MRI detection tool in a prostate tumor-bearing mouse model. NPs with an average diameter of 152.9 ± 15.7 nm (RS1) had a 2-fold enhancement of tumor specificity compared to larger (421.2 ± 33.8 nm) NPs (RS4). There was a 1.8-fold (P < 0.01) and 1.6-fold (P < 0.01) upregulation of the tumor-to-liver signal intensities of C-RS1 and C-RS4 (functionalized NPs) compared to controls, respectively. Also, tumor specificity was 3.1-fold higher (P < 0.001) when comparing C-RS1 to C-RS4. This detection tool improved tumor localization of contrast-enhanced MRI, supporting potential clinical applicability.
磁共振成像是检测前列腺癌的一种关键成像工具；然而，需要更好的、更专注于癌症特异性的工具来区分良性和恶性区域。我们发现，在高级别而非低级别人类前列腺癌活检中，claudin-3（CLDN-3）和-4（CLDN-4）的表达更高（n=174），这导致设计了具有非毒性截短版天然配体梭状芽胞杆菌肠毒素（C-CPE）的功能化纳米颗粒（NPs），该配体对 Cldn-3 和 Cldn-4 受体具有很强的结合亲和力。我们在前列腺肿瘤荷瘤小鼠模型中开发了首例基于 C-CPE-NP 的 MRI 检测工具。平均直径为 152.9±15.7nm（RS1）的 NPs 与较大的 NPs（421.2±33.8nm）相比，肿瘤特异性增强了 2 倍（RS4）。与对照相比，C-RS1 和 C-RS4（功能化 NPs）的肿瘤与肝脏信号强度分别增加了 1.8 倍（P<0.01）和 1.6 倍（P<0.01）。此外，当比较 C-RS1 与 C-RS4 时，肿瘤特异性提高了 3.1 倍（P<0.001）。该检测工具提高了对比增强 MRI 的肿瘤定位能力，支持其潜在的临床应用。
