A DNA Aptamer Targeting Cellular Fibronectin Rather Than Plasma Fibronectin for Bioimaging and Targeted Chemotherapy of Tumors

Abstract

Fibronectin (FN) is a well-established hallmark of epithelial-to-mesenchymal transition, and may serve as an omnipresent cancer biomarker regardless of the origins of tumor cells. An ssDNA aptamer (ZY-1) with highly selective binding affinity to mesenchymal stromal cells is previously developed, but the binding target of ZY-1 on the cells and the underlying mechanism is yet to be understood. Here, the identification of FN as the target protein of aptamer ZY-1 is reported for the first time and the mechanism of ZY-1 binding to cFN is explored. The data indicate that ZY-1 solely recognizes cellular fibronectin (cFN) rather than plasma fibronectin (pFN). The ZY-1 binding to cFN is explored through computational modeling and the competition of heparin in binding cFN owing to steric hindrance is confirmed. The in vitro assay and noninvasive in vivo fluorescence imaging results validate the specificity of ZY-1 in targeting cFN and sensitivity in detecting tumors. The ZY-1-mediated targeted cancer therapy using a proof-of-concept study with a ZY-1-based complex loaded with doxorubicin (Dox) is further proved. This study would facilitate more comprehensive studies of anti-FN aptamers in the imaging and treatment of tumors and other FN-associated diseases.

miR-200a-3p promotes the malignancy of endometrial carcinoma through negative regulation of epithelial-mesenchymal transition

“…Finally, ELISA was used to determine the changes in fibronectin (FN) and SNAIL proteins after regulation to clarify the other EMT-related protein changes in mice tumors after miR-200a-3p overexpression. FN and SNAlL are recognized as EMT-related proteins, depicting the enhanced invasion and metastasis ability of tumor cells [ 22 , 23 ]. The experimental results indicated that the expression of FN and SNAIL in tumors in the miR-200a-3p-overexpressing group was decreased.…”

Chemically Modified Platforms for Better RNA Therapeutics

“…Notably, the integration of siRNA with poly­(dimethylaminoethyl methacrylate) cationic polymer brushes coating, leveraging their unique physicochemical properties, has yielded high-performance theranostic probes . Additionally, aptamers have gained recognition as versatile agents in precision medicine, facilitating targeted drug therapy, , personalized treatments, molecular diagnostics, − tumor marker discovery, − bioanalysis, molecular pathology, , noninvasive screening, and bioimaging. , These recent advances in aptamer research hold tremendous potential for accelerating progress in precision medicine and modern biological applications. Besides, a novel regulatory network involving long noncoding RNAs (lncRNAs), miRNAs, and mRNAs, commonly known as the lncRNA-miRNA-mRNA axis, has been implicated in the pathophysiological processes of colorectal cancer and cardiovascular diseases .…”

Programmable melanoma-targeted radio-immunotherapy via fusogenic liposomes functionalized with multivariate-gated aptamer assemblies

“…Aptamer is a class of synthetic oligonucleotide ligands with antibody-like binding behavior with designated molecular targets 39 – 41 , which has attracted broad interest for therapeutic applications due to the high binding affinity/specificity and may fulfill a variety of functional roles including signaling mediators and targeting ligands, which are particularly favorable in the field of antitumor immunotherapeutics 42 – 46 . For example, CpG ODN (CpG oligonucleotide) is a clinically tested aptamer-based immune adjuvant that can promote DC activation via triggering toll-like receptor 9 (TLR9) immune signaling to stimulate the downstream adaptive immune reactions 47 – 49 .…”