A DNA-based nanocarrier for efficient cancer therapy.

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 cytotoxicity of CPT-DNA-NT than that of the free CPT due to the depot release of CPT after DNA-NT internalization. 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. [Display omitted] • Development of effective and safe vehicles for cytotoxic drug delivery into targeted tumor cells remained a significant challenge in the modern medicine. • Circular DNA nanotechnology is a tool to design architects with stiffer topology and geometry based on Watson-Crick base pairing for potential applications including drug delivery. • Cisplatin is loaded in DNA Nanothread (DNA NT) to achieve enhanced cytotoxicity and CPT-DNA-NT shows controlled/prolonged CPT release and enhanced cytotoxic activity through scavenger receptors facilitated endocytosis, making this a promising candidate for anticancer therapy. [ABSTRACT FROM AUTHOR]