Biomedical Engineering – From Theory to Applications

210
Biomedical Engineering – From Theory to Applications
detected tumor cell implants with only 1 × 10 4 tumor cells while MRI detected tumor cell
grafts containing 1 × 10 5 labeled cells (Figure 5).
Fig. 3. ScFvEGFR-conjugated IO nanoparticles show high specificity to EGFR-overexpressing
tumor cells and induce MRI signal changes in IO nanoparticle-bound tumor cells in vitro. A)
ScFvEGFR-IO nanoparticle construct consists of uniform IO nanoparticles (10 nm core size)
coated with amphiphilic copolymers modified with short PEG chains. ScFvEGFR proteins
were conjugated to the IO nanoparticles mediated by EDAC. B) Prussian blue staining
confirmed the specific binding of the ScFvEGFR-IO nanoparticles to tumor cells with EGFR
overexpression . C) T2 weighted MRI and T2 relaxometry mapping showed significant
decreases in MRI signals and T2 relaxation times in the cells bound with ScFvEGFR-IO
nanoparticles but not with GFP-IO nanoparticles or bare IO nanoparticles. MDA-MB-231
breast cancer cells and MIA PaCa-2 pancreatic cancer cells have different levels of EGFR
expression and different levels of T2 weighted contrast. A low T2 value correlates with a higher
iron concentration (red color), indicating higher level of specific binding of ScFvEGFR-IO
nanoparticles to tumor cells. D) Multi-echo T2 weighted fast spin echo imaging further
confirmed the fastest T2 value drop in MDA-MB-231 cells after incubation with ScFvEGFR-IO
but not with control GFP-IO nanoparticles. Reproduced with permission from Yang, L., H.
Mao, et al. (2009). "Single chain epidermal growth factor receptor antibody conjugated
nanoparticles for in vivo tumor targeting and imaging." Small 5(2): 235-43.