In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

Abstract

Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [ N , N -bis-stearylamidomethyl- N ′-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor.

Aptamers Against Live Targets: Is In Vivo SELEX Finally Coming to the Edge?

“…34 The GBI-10 aptamer was also used to guide gadolinium-loaded liposomes as a carrier of contrast agent in magnetic resonance imaging (MRI) for diagnosis and tumor therapy. 35 Recently, the GBI-10 aptamer has also been used to guide nanoparticles for therapy in pancreatic ductal adenocarcinoma (PDAC) that grew in an extracellular matrix (ECM) enriched in tenascin-C protein. 36 In this study, nanoparticles of camptothecin dimeric prodrug (CPTD) were encapsulated with cell-penetrating peptide (CPP) in order to increase the cellular drug uptake.…”