Alternatively spliced forms of fibronectin, called oncofetal fibronectin, are aberrantly expressed in cancer, with little to no expression in normal tissue, making them attractive biomarkers to exploit for tumor-targeted therapeutics and diagnostics. While prior studies have explored oncofetal fibronectin expression in limited cancer types and limited sample sizes, no studies have performed a large-scale pan-cancer analysis in the context of clinical diagnostics and prognostics to posit the utility of these biomarkers across multiple cancer types. In this study, RNA-Seq data sourced from the UCSC Toil Recompute project were extracted and analyzed to determine the correlation between the expression of oncofetal fibronectin, including extradomain A and extradomain B fibronectin, and patient diagnosis and prognosis.
View Article and Find Full Text PDFExtradomain-B Fibronectin (EDB-FN) is an oncomarker that can be visualized with magnetic resonance molecular imaging (MRMI) to detect pancreatic ductal adenocarcinoma (PDAC) metastasis. In this study, we sought to assess the expression of EDB-FN in clinical samples of PDAC and to evaluate MRMI of PDAC metastasis with an EDB-FN-specific gadolinium-based contrast agent (MT218) in an orthotopic KPC-GFP-Luc mouse model. EDB-FN expression was evaluated in PDAC tissue samples through immunohistochemistry.
View Article and Find Full Text PDFPharmaceuticals (Basel)
October 2021
Nucleic acids are promising for a variety of therapies, such as cancer therapy and the gene therapy of genetic disorders. The therapeutic efficacy of nucleic acids is reliant on the ability of their efficient delivery to the cytosol of the target cells. Amino lipids have been developed to aid in the cytosolic delivery of nucleic acids.
View Article and Find Full Text PDFPurpose: Oral squamous cell carcinoma (OSCC) has not seen a substantial improvement in patient survival despite therapeutic advances, making accurate detection and characterization of the disease a clinical priority. Here, we aim to demonstrate the effectiveness of magnetic resonance imaging (MRI) with the targeted MRI contrast agent MT218 specific to extradomain-B fibronectin (EDB-FN) in the tumor microenvironment for detection and characterization of aggressive OSCC tumors.
Procedures: EDB-FN expression was evaluated in human normal tongue and OSCC specimens with immunohistochemistry.
Nanoparticle based siRNA formulations often suffer from aggregation and loss of function during storage. We in this study report a frozen targeted RGD-polyethylene glycol (PEG)-ECO/siβ3 nanoparticle formulation with a prolonged shelf life and preserved nanoparticle functionality. The targeted RGD-PEG-ECO/siβ3 nanoparticles are formed by step-wised self-assembly of RGD-PEG-maleimide, ECO, and siRNA.
View Article and Find Full Text PDFLong noncoding RNAs (lncRNAs), by virtue of their versatility and multilevel gene regulation, have emerged as attractive pharmacological targets for treating heterogeneous and complex malignancies like triple-negative breast cancer (TNBC). Despite multiple studies on lncRNA functions in tumor pathology, systemic targeting of these "undruggable" macromolecules with conventional approaches remains a challenge. Here, we demonstrate effective TNBC therapy by nanoparticle-mediated RNAi of the oncogenic lncRNA DANCR, which is significantly overexpressed in TNBC.
View Article and Find Full Text PDFCRISPR/Cas9 system is a promising approach for gene editing in gene therapy. Effective gene editing requires safe and efficient delivery of CRISPR/Cas9 system in target cells. Several new multifunctional pH-sensitive amino lipids were designed and synthesized with modification of the amino head groups for intracellular delivery of CRISPR/Cas9 system.
View Article and Find Full Text PDFDevelopment of a gene delivery system with high efficiency and a good safety profile is essential for successful gene therapy. Here we developed a targeted non-viral delivery system using a multifunctional lipid ECO for treating Leber's congenital amaurosis type 2 (LCA2) and tested this in a mouse model. ECO formed stable nanoparticles with plasmid DNA (pDNA) at a low amine to phosphate (N/P) ratio and mediated high gene transfection efficiency in ARPE-19 cells because of their intrinsic properties of pH-sensitive amphiphilic endosomal escape and reductive cytosolic release (PERC).
View Article and Find Full Text PDFRNAi-mediated knockdown of oncogenes associated with drug resistance can potentially enhance the efficacy of chemotherapy. Here, we have designed and developed targeted dual pH-sensitive lipid-siRNA self-assembly nanoparticles, RGD-PEG(HZ)-ECO/siRNA, which can efficiently silence the oncogene, eukaryotic translation initiation factor 4E (eIF4E), and consequently resensitize triple-negative breast tumors to paclitaxel. The dual pH-sensitive function of these nanoparticles facilitates effective cytosolic siRNA delivery in cancer cells, both in vitro and in vivo.
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