Visual Investigation of Tumor‐Promoting Fibronectin Potentiated by Obesity in Pancreatic Ductal Adenocarcinoma Using an MR/NIRF Dual‐Modality Dendrimer Nanoprobe

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.

Dual-Modality Nanoprobe for Noninvasive Detection of Microthrombus after Cerebral Ischemia/Reperfusion

“…The attachment of orthopyridyl disulfide-poly­(ethylene glycol) 2000 - N -hydroxysuccinimide (OPSS-PEG 2000 -NHS) to PAMAM was confirmed by the peak at 1180 cm –1 , corresponding to the C–O stretch. Successful grafting of DTPA onto the PAMAM molecule was evidenced by the characteristic peak at 1413 cm –1 , corresponding to the carboxylate group. , These absorption peaks collectively validate the specific structure of GNC, which aligns with previous studies of our research group . The application of ultraviolet spectroscopy analysis revealed the presence of a distinct peak at 342 nm, corresponding to the mercaptopyridine group of OPSS in the purified supernatant, indicating that the CREKA peptide effectively displaced the OPSS group, thereby establishing successful conjugation of CREKA (Figure e).…”

“…In our research group's previous study, we conducted in vivo noninvasive imaging of extensively deposited fibrin in tumors. 46 The results of this investigation further confirm the specific microthrombus imaging capability of GNC with remarkably low usage amounts.…”

“…This further underscores the feasibility of employing the nanoprobes in severe disruption to the coagulation-fibrinolysis balance within the body. In our research group’s previous study, we conducted in vivo noninvasive imaging of extensively deposited fibrin in tumors . The results of this investigation further confirm the specific microthrombus imaging capability of GNC with remarkably low usage amounts.…”

“…44,45 These absorption peaks collectively validate the specific structure of GNC, which aligns with previous studies of our research group. 46 The application of ultraviolet spectroscopy analysis revealed the presence of a distinct peak at 342 nm, corresponding to the mercaptopyridine group of OPSS in the purified supernatant, indicating that the CREKA peptide effectively displaced the OPSS group, thereby establishing successful conjugation of CREKA (Figure 2e). A linear relationship between the probe concentration and optical signal intensity was observed, demonstrating the stable and consistent optical imaging capabilities of both nanoformulations (Figure 2f,g).…”

Chimeric Peptide‐Engineered Self‐Delivery Nanomedicine for Photodynamic‐Triggered Breast Cancer Immunotherapy by Macrophage Polarization

“…The hydrophilic peptide sequence of CREKA was used to target the delivery of nanomedicine to the tumor site. [ 40,41 ] Due to intermolecular interactions, free Ce6 and R837 could be self‐assembled into carrier‐free nanoparticles (designated as CeR). PEG 8 was used to regulate the self‐assembly behavior and enhance the stability of ChiP‐CeR.…”