Visual Investigation of Tumor-Promoting Fibronectin Potentiated By Obesity In Pancreatic Ductal Adenocarcinoma Using An Mr/Nirf Dual-Modality Dendrimer Nanoprobe.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease characterized by dense stroma. Obesity is an important metabolic factor that greatly increases PDAC risk and mortality, worsens progression and leads to poor chemotherapeutic outcomes. Withomics analysis, magnetic resonance and near-infrared fluorescence (MR/NIRF) dual-modality imaging and molecular functional verification, we proved that obesity as an important risk factor modulated the extracellular matrix (ECM) components and enhanced Fibronectin (FN) infiltration in the PDAC stroma, that promotes tumor progression and worsens response to chemotherapy by reducing drug delivery. In our study, to visually evaluate FN in vivo and guide PDAC therapy, we synthesized an FN-targeted nanoprobe, NP-CREKA, by conjugating gadolinium chelates, IR797 and fluorescein isothiocyanate to a polyamidoamine dendrimer functionalized with targeting peptides. A dual-modality strategy combining MR and NIRF imaging was applied, allowing effective visualization of FN in orthotopic PDAC with high spatial resolution, ideal sensitivity and excellent penetrability, especially in obese mice. In conclusion, our findings provide new insights into the potential of FN as an ideal target for therapeutic evaluation and improved treatment efficacy in PDAC, hopefully improving the specific management of PDAC in lean and obese hosts. This article is protected by copyright. All rights reserved.