Development of a diagnostic polymersome system for potential imaging delivery
2015
Abstract In order to enhance visualization of soft tissues, a dual-imaging diagnostic polymersome system featured with highly hydrated multilamellar wall structure capable of simultaneously embedding a hydrophobic near-infrared fluorophore, Cy5.5, and a paramagnetic probe, gadolinium (Gd(III)) cations was developed. The polymersomes were obtained from the self-assembly of lipid-containing copolymer, poly(acrylic acid-co-distearin acrylate), in aqueous solution. The Cy5.5 and Gd(III) species were loaded into polymersomes via hydrophobic association (loading efficiency of Cy5.5 ca 74%) and electrostatic complexation (Gd(III) 83%), respectively. The Cy5.5/Gd(III)-loaded polymersomes (CGLPs) have shown excellent payload confinement, reduced dilution effect on assembly dissociation and decreased protein/salt-induced colloidal aggregation. Owing to the highly hydrated structure of vesicular membrane, the superior contrast enhancement of CGLPs in magnetic resonance (MR) imaging was obtained as a result of prolonged rotational correlation time of Gd(III) cations and fast water exchange from Gd(III) to bulk solution. The CGLPs exhibit a 15-fold higher longitudinal relaxivity value ( ca 60 mM −1 s −1 ) than that (4 mM −1 s −1 ) of the commercial contrast agent, Magnevist, in phosphate buffered saline. The in vivo characterization demonstrates that CGLPs exhibit a signal-to-noise ratio in T 1 -weighted MR image contrast similar to that of Magnevist, yet with a Gd dose 5-fold lower. An excellent contrast in NIR imaging at tumor site was attained following the intravenous injection of GGLPs into Tramp-C1 tumor-bearing mice (C57BL/6). Along with their non-toxicity at the dose used, these results demonstrate the great potential of the CGLPs as an advanced diagnostic nanodevice.
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