1. Targeting prostate cancer with Clostridium perfringens enterotoxin functionalized nanoparticles co-encapsulating imaging cargo enhances magnetic resonance imaging specificity
- Author
-
Daniel P. Petrylak, Tarek M. Fahmy, Peter G. Schulam, Darryl T. Martin, Jung Seok Lee, Peter A. Humphrey, Gigi Galiana, Preston C. Sprenkle, Robert M. Weiss, Jeffery C. Weinreb, and Qiang Liu
- Subjects
Male ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,Enterotoxin ,medicine.disease_cause ,Prostate cancer ,Enterotoxins ,Mice ,Prostate ,medicine ,Animals ,Humans ,General Materials Science ,Receptor ,medicine.diagnostic_test ,Chemistry ,Cancer ,Prostatic Neoplasms ,Magnetic resonance imaging ,Clostridium perfringens ,medicine.disease ,Ligand (biochemistry) ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Cancer research ,Molecular Medicine ,Nanoparticles - Abstract
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.
- Published
- 2021