Synthetic development of cell-permeable polymer colloids decorated with nanocrystal imaging probes optimized for cell trackingElectronic supplementary information (ESI) available: Synthesis and characterization of all materials as well as cell labeling protocols and analysis. See DOI: 10.1039/c2sc20206a

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 mixed-component 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. Colloidal polymer vectors loaded with nanocrystals translocate otherwise membrane impermeable imaging probes to the cytosol of cells for cell tracking.