Bacteria-Mediated Intracellular Click Reaction for Drug Enrichment and Selective Apoptosis of Drug-Resistant Tumor Cells.

Functionalized biocarriers that can perform bio-orthogonal reactions in tumor cells may provide solutions to overcome the efflux of the chemotherapeutic agent from drug-resistant tumor cells. Herein, we report the enrichment of therapeutic drugs in tumor cells through intracellular click reaction with functionalized bacteria. Specifically, an intracellular bioactive drug enrichment template (OPV@ Escherichia coli ) is constructed by combining positively charged oligo(phenylene-vinylene)-alkyne (OPV-C≡CH) with E. coli via electrostatic interaction. After the cell uptake of OPV@ E. coli and Cu(II)-based complex, Cu(I) generated in situ can catalyze the bio-orthogonal click reaction to covalently anchor the azide-bearing molecules of cyanine 5 (Cy5-N 3 ) and paclitaxel (PTX-N 3 ) on OPV@ E. coli . These molecules and their functions were retained and enriched inside the drug-resistant tumor cells A549T, which can label cells with fluorescent probes and selectively induce the apoptosis of drug-resistant tumor cells.