DNA-Programmed Quantum Dot Polymerization for Ultrasensitive Molecular Imaging of Cancer Cells

Inorganic nanocrystals, such as quantum dots (QDs), hold great promise as molecular imaging contrast agents because of their superior optical properties. However, the molecular imaging sensitivity of these probes is far from optimized due to the lack of efficient and general method for molecular engineering of nanocrystal into effective bioprobes for signal-amplified imaging. Herein, we develop a strategy to boost the molecular imaging sensitivity of QDs over the limit by copolymerizing QDs and cell-binding aptamers into linear QD-aptamer polymers (QAPs) through DNA-programmed hybridization chain reaction. We show that the cancer cells treated with QAPs exhibit much stronger photoluminescence (PL) signal than those treated with QD-aptamer monomers (QAMs) because of multivalent binding and multi-QD-based signal amplification. The enhanced cell binding and imaging capacity of QAPs significantly improves imaging-based discrimination between different cancer cell types. This approach adds a new dimension for engineering inorganic nanoparticles into effective bioprobes for biomedical applications.