Poly(glycerol) Used for Constructing Mixed Polymeric Micelles as T1 MRI Contrast Agent for Tumor-Targeted Imaging
Yi Cao, Min Liu, Kunchi Zhang, Guangyue Zu, Ye Kuang, Xiaoyan Tong, Dangsheng Xiong, Renjun Pei
Abstract
There was much interest in the development of nanoscale delivery vehicles based on polymeric micelles to realize the diagnostic and therapeutic applications in biomedicine. Here, with the purpose of constructing a micellar magnetic resonance imaging (MRI) contrast agent (CA) with well biocompatibility and targeting specificity, two types of amphiphilic diblock polymers, mPEG-PG(DOTA(Gd))-b-PCL and FA-PEG-b-PCL, were synthesized to form mixed micelles by coassembly. The nanostructure of the resulting micellar system consisted of poly(caprolactone) (PCL) as core and poly(glycerol) (PG) and poly(ethylene glycol) (PEG) as shell, simultaneously modified with DOTA(Gd) chelates and folic acid (FA), which afforded functions of MRI contrast enhancement and tumor targeting. The mixed micelles in aqueous solution presented a hydrodynamic diameter of about 85 nm. Additionally, this mixed micelles exhibited higher r1 relaxivity (14.01 mM-1 S1-) compared with commercial Magnevist (3.95 mM-1 S1-) and showed negligible cytotoxicity estimated by WST assay. In vitro and in vivo MRI experiments revealed excellent targeting specificity to tumor cells and tissue. Furthermore, considerably enhanced signal intensity and prominent positive contrast effect were achieved at tumor region after tumor-bearing mice were intravenously injected with the mixed micelles. These preliminary results indicated the potential of the mixed micelle as T1 MRI CA for tumor-targeted imaging.
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Abbreviation: Alkyne-PEG-OH
Name: α-Alkynyl-ω-hydroxyl poly (ethylene glycol)
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