A DNA-based nanocarrier for efficient cancer therapy / 药物分析学报

ABSTRACT

The study aimed to achieve enhanced targeted cytotoxicity and cell-internalization of cisplatin-loaded deoxyribonucleic acid-nanothread (CPT-DNA-NT),mediated by scavenger receptors into HeLa cells.DNA-NT was developed with stiff-topology utilizing circular-scaffold to encapsulate CPT.Atomic force microscopy (AFM) characterization of the DNA-NT showed uniformity in the structure with a diameter of 50-150 nm and length of 300-600 nm.The successful fabrication of the DNA-NT was confirmed through native-polyacrylamide gel electrophoresis analysis,as large the molecular-weight (polymeric) DNA-NT did not split into constituting strands under applied current and voltage.The results of cell viability confirmed that blank DNA-NT had the least cytotoxicity at the highest concentration (512 nM) with a viability of 92％ as evidence of its biocompatibility for drug delivery.MTT assay showed superior cyto-toxicity of CPT-DNA-NT than that of the free CPT due to the depot release of CPT after DNA-NT inter-nalization.The DNA-NT exhibited targeted cell internalizations with the controlled intracellular release of CPT (from DNA-NT),as illustrated in confocal images.Therefore,in vitro cytotoxicity assessment through flow cytometry showed enhanced apoptosis (72.7％) with CPT-DNA-NT (compared to free CPT;64.4％).CPT-DNA-NT,being poly-anionic,showed enhanced endocytosis via scavenger receptors.