Original ArticleTargeting prostate cancer with Clostridium perfringens enterotoxin functionalized nanoparticles co-encapsulating imaging cargo enhances magnetic resonance imaging specificity
Graphical Abstract
We developed 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 the Cldn-3 and Cldn-4 receptors. The C-CPE NP-based MRI detection tool provided 70% tumor coverage using a prostate tumor-bearing mouse model.
Section snippets
Patient tissue specimens
All men were participants in the IRB approved Yale Urology Biospecimen and Data repository for prostate cancer. From August 2015 to December 2018 and within three months of receiving an mpMRI, an MRI-ultrasound fusion targeted biopsy of regions of interest (ROIs) and concurrent 12-core systematic biopsies under local anesthesia using the Artemis® biopsy device (Eigen, Grass Valley, CA) were performed. Biopsy cores were collected and immediately fixed. All biopsy cores were reviewed in a
Claudin expression and Decipher signature in human prostate cancer specimens
CLDN-3 mRNA expression in Gleason Grade Group 3+ (GG3+) (M = 1.313, SD = 0.385, n = 27) was higher than levels of expression in Gleason Grade Group 1 (GG1) (M = 1.014, SD = 0.278, n = 147), t(172) = 4.84, P < 0.0001, Cohen's d = 1.008 (Figure 1, A). CLDN-4 mRNA expression in Gleason GG3+ (M = 0.647, SD = 0.208) was higher than levels of expression in Gleason GG1 (M = 0.566, SD = 0.144), t(172) = 2.48, p = 0.014, Cohen's d = 0.520 (Figure 1, B). The Decipher signature in GG3+ (M = 0.624,
Discussion
MRI-US fusion technology has improved the detection of clinically significant prostate cancer. MRI-ultrasound has become the standard of clinical care to identify suspicious lesions within the prostate gland.5 We have biopsied over 1000 patients based on PI-RADS version 1 (v1) and version 2 (v2), with a cancer detection rate of 87%, which is comparable with other institutions including the University of California-Los Angeles (UCLA) at 80%30 and the University of Maryland at 92%.1 Even with the
Acknowledgements
The authors thank Drs. Emiliano Cocco, Richard Fan, and Alessandro D. Santin for initial project discussions. The authors also thank Dr. Hongliang Shen, Stellar Levy, and Mmaserame Gaefele for technical assistance, and Dr. Ashley M. Schnakenberg Martin for statistical assistance. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Prostate Cancer Research Program under Award No. W81XWH-14-1-0487 (DTM). The opinions, interpretations,
References (39)
- et al.
Prostate Imaging Reporting and Data System Version 2.1: 2019 update of Prostate Imaging Reporting and Data System Version 2
Eur Urol
(2019) - et al.
Nanoparticle therapeutics for prostate cancer treatment
Maturitas
(2012) - et al.
Surface modification of biodegradable polyesters with fatty acid conjugates for improved drug targeting
Biomaterials
(2005) - et al.
Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer
Nanomedicine
(2013) An overview of Clostridium perfringens enterotoxin
Toxicon
(1996)- et al.
Enhancement of surface ligand display on PLGA nanoparticles with amphiphilic ligand conjugates
J Control Release
(2011) - et al.
Acquired resistance of EGFR-mutant lung adenocarcinomas to afatinib plus cetuximab is associated with activation of mTORC1
Cell Rep
(2014) - et al.
The value of ESWAN in diagnosis and differential diagnosis of prostate cancer: preliminary study
Magn Reson Imaging
(2017) - et al.
Multifocality and prostate cancer detection by multiparametric magnetic resonance imaging: correlation with whole-mount histopathology
Eur Urol
(2015) - et al.
Polymersomes for drug delivery: design, formation and characterization
J Control Release
(2012)
Circulation kinetics and biodistribution of dual-labeled polymersomes with modulated surface charge in tumor-bearing mice: comparison with stealth liposomes
J Control Release
Effect of liposome size on the circulation time and Intraorgan distribution of amphipathic poly(ethylene glycol)-containing liposomes
BBA-Biomembranes
Peptide-conjugated nanoparticles for targeted imaging and therapy of prostate cancer
Biomaterials
Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer
JAMA
Targeted prostate biopsy: value of multiparametric magnetic resonance imaging in detection of localized cancer
Asian J Androl
Evaluation of new tests and interventions for prostate cancer management: a systematic review
J Natl Compr Cancer Netw
A review of imaging methods for prostate cancer detection
Biomed Eng Comput Biol
Dysprosium-modified tobacco mosaic virus nanoparticles for ultra-high-field magnetic resonance and near-infrared fluorescence imaging of prostate cancer
ACS Nano
Targeting and cellular trafficking of magnetic nanoparticles for prostate cancer imaging
Mol Imaging
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Competing interests: There are no competing interests to report.
- 1
Contributed equally to this work.
- 2
Present address: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, China.