A water-soluble fluorescent hyperbranched conjugated polyelectrolyte (HCPE) with a unique double-layered architecture is synthesized via the combination of alkyne polycyclotrimerization and alkyne-azide "click" reaction for live-cell imaging. Because of the rigid conjugated core that offers shape persistence, and the water-soluble nonionic poly(ethylene glycol) shells that passivate the macromolecular surface, HCPE intrinsically forms single-molecular core-shell nanospheres with an average diameter of ~10.7 nm and a narrow size distribution of ~1.5, according to transmission electron microscopy images. The resulted organic nanospheres possess high quantum yield (30% in buffer), good solution stability, and low cytotoxicity. Using breast cancer cell MCF-7 as an example, these core-shell nanospheres are internalized efficiently by the cells and accumulated in the cytoplasm to give bright fluorescence. Photostability study reveals that these nanospheres are significantly more stable than commercial dyes, such as fluorescein, rhodamine, and Cy5, which demonstrates the great potential of organic polymeric nanomaterials in long-term clinical applications. In addition, the state-of-the-art synthetic methods used herein provide the feasibility and flexibility to modify both core and shell components of HCPE for specific biological applications.
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