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. With omics analysis, magnetic resonance and near-infrar...

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Bibliographic Details
Published in:Advanced healthcare materials 2023-10, Vol.12 (25), p.e2300787-e2300787
Main Authors: Xu, Tingting, Xu, Xiaoxuan, Liu, Dongfang, Chang, Di, Li, Siqi, Sun, Yeyao, Xie, Jinbing, Ju, Shenghong
Format: Article
Language:English
Subjects:
Adenocarcinoma
Chelates
Chemotherapy
Drug delivery
Extracellular matrix
Fibronectin
Fluorescein isothiocyanate
Gadolinium
In vivo methods and tests
Infrared analysis
Magnetic resonance imaging
Metastases
Obesity
Pancreas
Pancreatic cancer
Peptides
Risk factors
Spatial discrimination
Spatial resolution
Stroma
Tumors
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Summary: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. With omics analysis, magnetic resonance and near-infrared fluorescence (MR/NIRF) dual-modality imaging and molecular functional verification, obesity as an important risk factor is proved to modulate the extracellular matrix (ECM) components and enhance Fibronectin (FN) infiltration in the PDAC stroma, that promotes tumor progression and worsens response to chemotherapy by reducing drug delivery. In the study, to visually evaluate FN in vivo and guide PDAC therapy, an FN-targeted nanoprobe, NP-CREKA, is synthesized by conjugating gadolinium chelates, NIR797 and fluorescein isothiocyanate to a polyamidoamine dendrimer functionalized with targeting peptides. A dual-modality strategy combining MR and NIRF imaging is applied, allowing effective visualization of FN in orthotopic PDAC with high spatial resolution, ideal sensitivity and excellent penetrability, especially in obese mice. In conclusion, the findings provide new insights into the potential of FN as an ideal target for therapeutic evaluation and improving treatment efficacy in PDAC, hopefully improving the specific management of PDAC in lean and obese hosts.
ISSN:2192-2640
2192-2659
DOI:10.1002/adhm.202300787