US scientists have developed a method to deliver probes into cells to track the cells. Therapies such as those based on stem cells that require whole body tracking using non-invasive imaging, for example magnetic resonance imaging (MRI), would benefit from the probes.
Current nanoparticle-based tracking systems rely on probes entering cells passively, which is inefficient because the probes often get sequestered in endosomes (compartments in cells that sort molecules for degradation or recycling back to the cell membrane). Now, a team from the Lawrence Berkeley National Laboratory led by Brett Helms has avoided this problem by coating a nanocrystal probe with a polymer vector colloid and attaching guanidine and amine groups to the polymer so that the whole thing mimics a virus.
'In this manner, we would be able to recapitulate a virus' ability to quickly enter cells - in our case, with nanocrystal imaging probes as cargo,' explains Helms. Nanocrystal probes are desirable because they can be tailored for specific imaging techniques such as MRI or whole-body fluorescence imaging.
The team also found that as well as providing an exceptionally fast cell-entry trajectory, the coating prevented the nanocrystal cargo from having a negative impact on long-term cell health. 'We hypothesised that this is related to the shorter residence time of the vector-bound nanocrystals in endosomes, where they can degrade in the acidic microenvironment into toxic ions,' explains Helms, 'and the ability of the vector to keep the nanocrystals from diffusing widely in the cell's interior, where they can be expected to disrupt cellular processes.'
'The colloidal polymer vectors will make a significant difference in the field of cancer biology, as they present an unique opportunity to track different cell types in vivo for analysis,' says Eva Harth, an expert in developing vectors for imaging reagents at Vanderbilt University, US. 'The combination of nanocrystal confinement in the colloidal vector, rapid uptake and a high overall nanocrystal concentration in intact cells makes the luminescence of the localisation pattern in the cystosol [the liquid inside cells] much more intense. With this, an entire new arena of in vivo cell tracking and analysis is possible and can be further developed for other imaging devices with greater tissue depth.'
Helms' team now plans to implant and image probes in mice to prove that they are ready to be used for cell tracking.
- D S Chahal et al, Chem. Sci., 2012, DOI: 10.1039/c2sc20206a