Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 14, Issue 10, Pages 12106-12115Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c01493
Keywords
bacterial template; intracellular catalysis; bio-orthogonal chemistry; drug enrichment; tumor drug resistance
Funding
- National Natural Science Foundation of China [22021002, 22022705, 22020102005]
- Beijing Natural Science Foundation [2222042]
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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.
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.
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