Molecular probes that selectively latch onto tumor cells and emit imaging signals can detect cancer without invasive procedures. These tools, however, have specific deficiencies. Fluorescent probes that image individual molecules have poor depth penetration into cells. The alternative, magnetic resonance imaging (MRI) probes, resolves cells in three dimensions but with low resolution. Bin Liu at the A*STAR Institute of Materials Research and Engineering, Singapore, and co-workers have now solved this problem with a biocompatible polymer that combines MRI and fluorescence imaging in a single molecular probe.
According to Liu, designing a probe with joint imaging capabilities is challenging because fluorescent and MRI-active materials display different biological behaviors. Substances that emit fluorescent light are often lethal to cells at low concentrations. In contrast, to produce sufficient imaging signals, MRI probes require substantial injections of substances called chelated gadolinium (Gd(III)) agents.
Liu and her team devised a strategy to overcome the dissimilar dosage requirements with polymers known as 'hyperbranched' polyglycerols (HPGs). These materials have a tree-like structure of repeating molecular units that radiate from a core. HPGs also have a promising biomedical track record because of their water solubility and low cytotoxicity. Liu and co-workers envisaged using HPGs to encapsulate fluorescent organic molecules as their core. Then, they reasoned, high densities of Gd(III) agents could attach to the numerous hydroxyl attachment points present on the HPG surfaces.
After synthesizing a fluorescent molecule consisting of fused aromatic rings, the researchers attached eight of them to a rigid polysilicate cage, known as polyhedral oligomeric silsesquioxane. With the stable core in place, they initiated growth and outward branching of the HPG into a spherical protective shell—a tricky procedure, notes Liu, as it required carefully controlling the reagents and polymerization conditions. The new nanospherical probe converted over 50% of light photons into fluorescent emissions, a remarkably high quantum yield arising from the water-repellent nature of the dense HPG shell.
Next, the team attached Gd(III) agents to the probe's exterior and tested its dual detection capabilities inside MCF-7 breast cancer cells. Both MRI and fluorescence imaging revealed that the nanoprobe was well integrated into cell structures with no obvious changes to cell viability. The probe demonstrated high photostability when exposed to laser light—a key attribute for fluorescence imaging—and had promising magnetic properties that compared favorably with commercial MRI probes. "Combining both imaging techniques in one probe simultaneously boosts resolution and penetration depth," says Liu. "The different signals can also validate each other to improve detection accuracy."
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Liu, J., et al. Single molecular hyperbranched nanoprobes for fluorescence and magnetic resonance dual modal imaging. Polymer Chemistry 4, 1517–1524 (2013). dx.doi.org/10.1039/C2PY20837G