Advanced Detection of Pancreatic Cancer Circulating Tumor Cells Using Biomarkers and Magnetic Particle Spectroscopy

<b>Background:</b> Pancreatic ductal adenocarcinoma (PDAC) typically develops without symptoms, and its aggressive progression combined with late-stage diagnosis underscores the critical need for improved early detection strategies. Circulating tumor cells (CTCs) in blood are potential biomarkers for PDAC. In this study, the detection of pancreatic cancer-associated CTCs was evaluated using two magnetic-based diagnostic systems in a comparative approach. <b>Methods:</b> Two distinct nanotheranostic platforms were developed: monoclonal antibody-conjugated magnetic nanoparticles (mAbs-MNPs) and magnetized exosomes (termed Magxosomes). Anti-mesothelin and anti-vimentin were used as monoclonal antibodies, while mesenchymal stem cells (MSCs) treated with MNPs served as the source of Magxosomes. Characterization of nano-systems was performed using dynamic light scattering (DLS), inductively coupled plasma mass spectrometry (ICP-MS), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). Blood samples were collected from pancreatic cancer mouse models, treated with nanotheranostic platforms, and analyzed using a homemade magnetic particle spectroscopy (MPS) device. <b>Results:</b> The detection of pancreatic cancer-associated CTCs was investigated using nanotheranostic platforms alongside an MPS instrument. In this context, the mAbs-MNPs systems demonstrated varying efficiencies in the diagnosis of CTCs, with Ant-V-MNPs (anti-vimentin conjugated MNPs) achieving 27.47%, Ant-M-MNPs (anti-mesothelin conjugated MNPs) at 13.59%, and a 50:50 mixture of Ant-M-MNPs: Ant-V-MNPs showing an efficiency of 19.73%. Conversely, the efficiencies of Magxosomes were notably higher. Bone marrow stem cell (BMSC)-derived Magxosomes achieved an average efficiency of 63.39%, while adipose-derived stem cell (ADSC)-derived Magxosomes exhibited an average efficiency of 56.23%. <b>Conclusions:</b> This study introduces a promising method for early pancreatic cancer diagnosis by detecting CTCs in blood. It employs a non-invasive, rapid test using an advanced MPS instrument (1 ng detection limit) and nanotheranostic platforms. Results confirm the system's robustness in identifying pancreatic cancer CTCs. This approach may support future developments in cancer diagnostics and monitoring.