Targeting fibronectin for cancer imaging and therapy

Abstract

During cancer progression, the extracellular matrix (ECM) undergoes dramatic changes, which promote cancer cell migration and invasion. In the remodeled tumor ECM, fibronectin (FN) level is upregulated to assist tumor growth, progression, and invasion. FN serves as a central organizer of ECM molecules and mediates the crosstalk between the tumor microenvironment and cancer cells. Its upregulation is correlated with angiogenesis, cancer progression, metastasis, and drug resistance. A number of FN-targeting ligands have been developed for cancer imaging and therapy. Thus far, FN-targeting imaging agents have been tested for nuclear imaging, MRI, and fluorescence imaging, for tumor detection and localization. FN-targeting therapeutics, including nuclear medicine, chemotherapy drugs, cytokines, and photothermal moieties, were also developed in cancer therapy. Because of the prevalence of FN overexpression in cancer, FN targeting imaging agents and therapeutics have the promise of broad applications in the diagnosis, treatment, and image-guided interventions of many types of cancers. This review will summarize current understanding on the role of FN in cancer, discuss the design and development of FN-targeting agents, and highlight the applications of these FN-targeting agents in cancer imaging and therapy.

In Operando Self‐Healing of Perovskite Electrocatalysts: A Case Study of SrCoO3 for the Oxygen Evolution Reaction

“…This barrier is also much lower than other perovskites such as LaCoO 3 or LaMnO 3 . [25,29] Therefore, surface V O can approach O*, which can then easily drop into the vacancy. These steps are illustrated in Figure 3.…”

Targeted Contrast Agent Specific to an Oncoprotein in Tumor Microenvironment with the Potential for Detection and Risk Stratification of Prostate Cancer with MRI

“…Clinical evidence demonstrates that EDB-FN is highly expressed in high-risk prostate cancer, low in benign lesions, including benign prostatic hyperplasia (BPH) 18–20 . Therefore, EDB-FN is a promising target for early detection and differential localization of high-risk prostate tumor with molecular imaging 21 . Recently, we have identified a small peptide ZD2 (Thr-Val-Arg-Thr-Ser-Ala-Asp) for specific targeting of EDB fragment using phage display 22 .…”

Magnetic resonance molecular imaging for non-invasive precision cancer diagnosis

“…Extradomain B-fibronectin (EDB-FN) is a cancer-related fibronectin isoform highly expressed in the ECM of various aggressive human cancers, but not in normal tissues [19, 20]. It is a marker of epithelial-to-mesenchymal transition (EMT) and plays a key role in EMT induction, cancer cell stemness, cancer proliferation, and angiogenesis.…”

“…Moreover, its expression is inversely correlated with patient survival [21, 22]. Molecular MRI of EDB-FN with ZD2-[Gd(HP-DO3A)] can effectively detect and differentiate aggressive prostate tumors in mouse xenograft models [20]. ZD2-[Gd(HP-DO3A)], a small molecular targeted contrast agent specific to EDB-FN, is synthesized by conjugating ZD2 peptide to a clinical contrast agent Gd(HP-DO3A).…”