Engineering a customized nanodrug delivery system at the cellular level for targeted cancer therapy
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摘要:
Drug administration customized to individual cells could intrinsically address cancer heterogeneity and provide a safe and effective method for delivering personalized treatment.To accomplish this,we developed a smart nanodrug delivery system characterized by cancer cell-targeted drug delivery and intracellular biomarker-responsive drug activation.This system was composed of a long-nicked DNA duplex formed by tandem hybridization of two extended antisense oligonucleotides whose ends were separately blocked with a cancer cell-specific aptamer,AS1411,and a replaceable anti-biomarker probe (ABP).We demonstrated that this DNA nanodrug was directed to cancer cells with the guidance power of AS1411 and then activated by the presence of a given intracellular biomarker.By using such a belt-and-braces strategy,this DNA nanodrug system could safely and efficiently accelerate apoptosis of target cancer cells.Moreover,since the expression level of biomarkers tends to indicate the specific physiological state of individual cells,biomarker-responsive activation of the nanodrug is expected to enable customized drug administration at the cellular level.