Dual-Modal Tumor Imaging via Long-Circulating Biodegradable Core-Cross-Linked Polymeric Micelles

We present a long-circulating biodegradable core-cross-linked polymeric micelle (d-CCPM) for the nuclear/optical imaging of tumors. The d-CCPM was derived from an amphiphilic block-copolymer consisting of a hydrophilic block of brush-like poly(ethylene glycol) and a hydrophobic block containing cleavable pendant triethoxysilane. The resultant imaging tracer had prolonged circulation in the blood (half-life of clearance phase = 36.5 h), substantial accumulation in tumors (% injected dose per gram of tissue = 8.5% ± 1.0% at 24 h postinjection), and minimal uptake in the liver (5.0% ± 0.1%) or spleen (5.1% ± 0.3%). Both nuclear and near-infrared fluorescence (NIRF) imaging revealed strong signals in tumor regions. At 48 h, nuclear imaging exhibited tumor-to-liver and tumor-to-blood ratios of 1.4 and 1.1, respectively. The degradation of d-CCPM was studied in vitro at pH 5.0 and 37 °C and confirmed by transmission electron microscopy. Our study indicates that the d-CCPM system is an effective probe for dual-m...