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High Throughput Nanoparticle Delivery to the Cytosol of Living Cells




Brett Helms and colleagues at Berkeley Lab have developed a material for rapidly and efficiently delivering nanoparticles to the cytosol of living cells. The material, a cationic core-shell polymer colloid, addresses the common problem whereby nanoparticles designed for subcellular labeling remain confined to endosomal vesicles, where they cannot reach their intended targets. With the new material, cytosolic labeling can be achieved with picomolar concentrations of commercially available or customized nanoparticles within a few hours of incubation, across a broad range of cell types.

The material is simple to use. Nanoparticles of interest are first introduced to the colloids, which serve as vectors into the cell. When incubated with cells, the nanoparticle-loaded colloids are readily endocytosed. As the endosomes are acidified, the polymer colloids rapidly expand in volume, causing endosomal rupture and, thus, release of the nanoparticles into the cytosol. The amount of cytosolic labeling is readily controlled by changing the initial nanoparticle concentration. In addition, the nanoparticles could potentially be tagged with biomolecular targeting agents to direct them to specific intracellular molecules or organelles. Thus, the colloids should dramatically simplify how researchers carry out, for example, single nanoparticle tracking experiments, the monitoring of molecular interactions in living cells, or early detection of disease markers in extracted tissues.

Nanoparticles offer several potential advantages over fluorescent dyes and immunofluorescent stains, such as a long luminescence lifetime, photostability and near quantitative light emission at specific, preselected wavelengths. However, until now, these advantages were often not realized because cytosolic delivery of nanoparticles was inefficient, labor intensive, and often harmful to cells. The Berkeley Lab material overcomes these limitations allowing nanoparticles to be used to examine cellular processes for longer periods than has been possible with organic chromophores. As such, the scheme is ideal for imaging live specimens.

STATUS: Patent pending. Available for licensing or collaborative research.

DEVELOPMENT STAGE: Bench scale prototypes tested.


Bayles, A.R., H.S. Chahal, D.S. Chahal, C.P. Goldbeck, B E. Cohen, B. A. Helms. "Rapid cytosolic delivery of luminescent nanocrystals in live cells with endosome-disrupting polymer colloids," Nano Letters. 10:4086-4092.


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