Detection of Pancreatic Ductal Adenocarcinoma by Ex Vivo Magnetic Levitation of Plasma Protein-Coated Nanoparticles.

Luca Digiacomo,Damiano Caputo,Giulio Caracciolo,Daniela Pozzi,Erica Quagliarini,Barbara Sartori,Heinz Amenitsch,Alessandro Coppola,Vincenzo La Vaccara,Roberto Coppola

doi:10.3390/cancers13205155

Abstract

Simple SummaryPancreatic Ductal Adeno Carcinoma (PDAC) is a highly lethal disease, for which mortality closely parallels incidence. The poor prognosis of PDAC is mainly due to cancer’s biological behavior and its advanced stage at the moment of the diagnosis. Despite strong efforts in the scientific community, reaching an effective early diagnosis is still a big challenge. Our research aims to develop highly sensitive and specific technologies for the early diagnosis of PDAC using magnetic levitation (MagLev) of nanoparticles coated by the personalized protein corona, i.e., the protein layer of plasma proteins that bind to nanomaterials exposed to patients’ bodily fluids. MagLev does not rely on critical experimental steps (e.g., isolating plasma proteins from nanoparticles) and thus overcomes limitations that propagate biases, hinder reproducibility, and typically impair clinical translation of medical technologies.Pancreatic Ductal Adeno Carcinoma (PDAC) is one of the most lethal malignancies worldwide, and the development of sensitive and specific technologies for its early diagnosis is vital to reduce morbidity and mortality rates. In this proof-of-concept study, we demonstrate the diagnostic ability of magnetic levitation (MagLev) to detect PDAC by using levitation of graphene oxide (GO) nanoparticles (NPs) decorated by a biomolecular corona of human plasma proteins collected from PDAC and non-oncological patients (NOP). Levitation profiles of corona-coated GO NPs injected in a MagLev device filled with a paramagnetic solution of dysprosium(III) nitrate hydrate in water enables to distinguish PDAC patients from NOP with 80% specificity, 100% sensitivity, and global classification accuracy of 90%. Our findings indicate that Maglev could be a robust and instrumental tool for the early detection of PDAC and other cancers.

Highlights

Licensee MDPI, Basel, Switzerland.Pancreatic Ductal Adeno Carcinoma (PDAC) is a highly lethal [1], worldwide increasing [2] disease predicted to be the second cause of cancer-related deaths in the decade [3]
The only PDAC biomarker approved by the US Food and Drug Administration (FDA) is carbohydrate antigen (CA) 19.9, but it exhibits non-adequate sensitivity (60–70%) and specificity (70–85%) values [8]
We present as a proof of concept the possibility to evaluate differences among the levitation patterns of Graphene Oxide (GO)-protein corona (PC) complexes obtained from non-oncological patients (NOP)

Summary

Introduction

Licensee MDPI, Basel, Switzerland.Pancreatic Ductal Adeno Carcinoma (PDAC) is a highly lethal [1], worldwide increasing [2] disease predicted to be the second cause of cancer-related deaths in the decade [3]. PDAC is often asymptomatic in its early stages or presents non-specific symptoms [5]. In most cases, surgery is precluded for patients, because of the presence of distant metastases or invasion of vascular structures at the moment of the diagnosis [7]. For these reasons, the early diagnosis of PDAC would represent an important gap to fill in the treatment of this disease, on the other hand, complementary tests could aid in the diagnosis and play a role in surveillance intervals. Researchers have been aiming at identifying new sensitive PDAC biomarkers in the last few years, thanks to the improvement of molecular technologies such as genetic sequencing, transcriptomic expression profiling, metabolomics, proteomics [9,10,11], and glycomics [12]

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