基质
纳米探针
胰腺癌
癌症研究
细胞外基质
体内
医学
异硫氰酸荧光素
纤维连接蛋白
癌症
病理
材料科学
内科学
免疫组织化学
生物
纳米技术
细胞生物学
生物技术
物理
量子力学
纳米颗粒
荧光
作者
Tingting Xu,Xiaoxuan Xu,Dongfang Liu,Di Chang,Siqi Li,Yeyao Sun,Jinbing Xie,Shenghong Ju
标识
DOI:10.1002/adhm.202300787
摘要
Abstract 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.
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