Luminescent nanocrystals hold great potential for bioimaging because of their exceptional optical properties, but their use in live cells has been limited. When nanocrystals enter live cells, they are taken up in vesicles. This vesicular sequestration is persistent and precludes nanocrystals from reaching intracellular targets. Here, we describe a unique, cationic core-shell polymer colloid that translocates nanocrystals to the cytosol by disrupting endosomal membranes via a low-pH triggered mechanism. Confocal fluorescence microscopy and flow cytometry indicate that picomolar concentrations of quantum dots are sufficient for cytosolic labeling, with the process occurring within a few hours of incubation. We anticipate a host of advanced applications arising from efficient cytosolic delivery of nanocrystal imaging probes: from single particle tracking experiments to monitoring protein-protein interactions in live cells for extended periods.

With recent advances in stem cell therapies and oncological research, prolonged tracking of single cells in vivo is critical to understanding their unusual biology. To tag these cells, nanocrystal-based probes are highly desirable since their composition can be tailored for specific imaging techniques, such as magnetic resonance imaging or whole-body fluorescence imaging. Nevertheless, a robust strategy to incorporate nanocrystals to the cytosol of living cells for tracking schemes has been difficult to achieve. We report here a biomimetic approach to nanocrystal delivery, ideally suited for cell tracking schemes, using a unique class of core-shell colloidal polymer vectors decorated with both amine and guanidine functionalities. These materials exhibit unusual dual responsive character to both pH and temperature that can be leveraged to translocate nanocrystal/polymer assemblies to the cytosol in less than an hour. By avoiding prolonged exposure to the acidic microenvironment of late endosomes, the intact nanocrystals no longer pose a problem to cell health. Such a rapid trajectory for these mixedcomponent assemblies into live cells is unprecedented and should make practical a wider array of nanoparticle-based tracking schemes in biological systems than is currently possible.

Directed delivery of mesoscaled cargo—for example, nanocrystals, proteins, or nucleic acids—to cells using polymer vectors impacts numerous biomedical fields. We introduce here the concept of dynamic complementarity as a simple, yet powerful approach to control the rate of mesoscaled cargo dissociation from colloidal polymer vectors once inside the cytosol. By tuning the degree of electrostatic reciprocity between the polymer vector and its cargo, it is possible to both deliver and release large cargo in live cells in a controllable manner over both long and short periods, pointing to a highly modular materials platform with molecularly tailored properties suited to task. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 256–264