Abstract
A cancer-recognizable MRI contrast agents (CR-CAs) has been developed using pH-responsive polymeric micelles. The CR-CAs with pH sensitivity were self-assembled based on well-defined amphiphilic block copolymers, consisting of methoxy poly(ethylene glycol)-b-poly(l-histidine) (PEG-p(l-His)) and methoxy poly(ethylene glycol)-b-poly(l-lactic acid)-diethylenetriaminopentaacetic acid dianhydride-gadolinium chelate (PEG-p(l-LA)-DTPA-Gd). The CR-CAs have a spherical shape with a uniform size of ∼40 nm at physiological pH (pH 7.4). However, in acidic tumoral environment (pH 6.5), the CR-CAs were destabilized due to the protonation of the imidazole groups of p(l-His) blocks, causing them to break apart into positively charged water-soluble polymers. As a result, the CR-CAs exhibit highly effective T1 MR contrast enhancement in the tumor region, which enabled the detection of small tumors of ∼3 mm3in vivo at 1.5 T within a few minutes.
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