Targeting prostate cancer with clostridium perfringens enterotoxin functionalized nanoparticles co-encapsulating imaging cargo enhances magnetic resonance imaging specificity.

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±15.7nm (RS1) had a 2-fold enhancement of tumor specificity compared to larger (421.2±33.8nm) 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) 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.

Nanomedicine : nanotechnology, biology, and medicine. 2021 Nov 02 [Epub ahead of print]

Darryl T Martin, Jung Seok Lee, Qiang Liu, Gigi Galiana, Preston C Sprenkle, Peter A Humphrey, Daniel P Petrylak, Jeffery C Weinreb, Peter G Schulam, Robert M Weiss, Tarek M Fahmy

Departments of Urology, Yale University, New Haven, CT. Electronic address: ., Department of Biomedical Engineering, Yale University, New Haven, CT., Departments of Urology, Yale University, New Haven, CT., Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT., Department of Pathology, Yale University, New Haven, CT., Departments of Urology, Yale University, New Haven, CT; Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.

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