Pancreatic cancer (PC) and pancreatic ductal adenocarcinoma (PDAC) are the most aggressive cancers worldwide. Surgery represents the only potential curative treatment. The PDAC aggressiveness is related to its biological features. Four different PDAC classes have been identified based on different molecular patterns (squamous; abnormally differentiated endocrine exocrine; pancreatic progenitor; immunogenic) showing differences in patients¿ survival. The protein expressions of most relevant genes may be used to find PDAC in the body. This puts hope in translational research to explore new strategies changing the disease course. Cancer nanotechnology developments in the theranostic probes area provide a new avenue to detect and treat PC. The development of nanoparticles (NP), for diagnosis and therapy, has attracted attention. Indocyanine green (ICG) is a dye, approved by the Food and Drug Administration, for clinical applications. Intravenously, ICG binds serum proteins, and the complexes transiently accumulate in tumors via nonspecific enhanced permeability and retention effect. Protein-bound ICG has absorption in the near-infrared (NIR) spectra, making it suitable for bio-imaging applications. In addition, ICG can be used as a photosensitiser to generate reactive oxygen species damaging cancer cells by illumination. The absorbed light can also heat the cellular microenvironment, by localized hyperthermia and destroying cancer cells. ICG is considered a promising theranostic agent. An ideal ICG NP for imaging-guided therapy in cancer would have abilities including: early visualization of tumors, effective delivery of drugs and theranostic agents, and optimized therapeutic strategy. This project is focused on ICG biological tracer conjugated with antibodies (Ab) against markers of the 4 classes of PDAC, to build a probe to detect PDAC epithelial cells using a source of infrared highlighting ICG, for image guided surgery in order to improve the margin status.
NEMEsiS aims to improve the surgical treatment of PDAC patients in order to reduce the percentage of R1 resection and prevent the surgical over-treatment for metastatic PDAC patients. Indeed, using specific tracer for more aggressive sub-classes of PDAC, a real tailored surgery might be possible according to the biological behavior of the disease.
NEMEsiS project may really open the new era of molecular surgery, in which the ICG-conjugated markers might highlight the "dark side of the moon" during surgical procedure. Nevertheless, the discovery of proteins associated with different outcomes of PDAC patients, could open a new era of diagnostic procedures based on the molecular phenotypes of pancreatic cancers.
NEMEsiS could increase the production of FDA approved tracer in order to discover primary tumor and metastases, not only for PDAC, but for other cancers too.
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