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

Functionalized biocarriers that can perform bioorthogonal reactions in tumor cells may provide solutions to overcome the efflux of the chemotherapeutic agent from drugresistant 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 S (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.

Automated summary

This study reports the enrichment of therapeutic drugs in tumor cells through intracellular click reaction with functionalized bacteria. Functionalized biocarriers, constructed by combining positively charged oligo(phenylene-vinylene)-alkyne with E. coli, can retain and enrich drug molecules inside drug-resistant tumor cells, providing a solution to overcome drug efflux and selectively induce apoptosis.