Development of a diagnostic polymersome system for potential imaging delivery.
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 T1-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.
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
Wen-Chia
WC
Huang
Biomedical Technology and Device Research Laboratory, Industrial Technology Research Institute, Hsinchu 300, Taiwan.
Yung-Chu
YC
Chen
Biomedical Technology and Device Research Laboratory, Industrial Technology Research Institute, Hsinchu 300, Taiwan.
Yuan-Hung
YH
Hsu
Biomedical Technology and Device Research Laboratory, Industrial Technology Research Institute, Hsinchu 300, Taiwan. Electronic address: hsiehw@itri.org.tw.
Wen-Yuan
WY
Hsieh
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan. Electronic address: hscchiu@mx.nthu.edu.tw.
Hsin-Cheng
HC
Chiu
D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D001692:Biological Transport; D002232:Carbocyanines / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry; D004075:Diglycerides / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D005456:Fluorescent Dyes / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods*; D009368:Neoplasm Transplantation; D058105:Polymerization; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000473:pathology*
D000180:Acrylic Resins; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D003287:Contrast Media; D004075:Diglycerides; D005456:Fluorescent Dyes; C006903:carbopol 940; D005682:Gadolinium
Cancer diagnosis; Diagnostic polymersomes; Magnetic resonance imaging (MRI); Near-infrared (NIR) imaging