Said Abasse Kassim,
Southeast University, China
Title: Design synthesis and evaluation of a novel DNA nanothread based Cisplatin delivery system through scavenger receptors for high-efficiency anti-cancer therapy
Biography
Biography: Said Abasse Kassim,
Abstract
To develop nucleic-acid based nanocarrier for cytotoxic-drug through self-assembly of designed sequences of artificial DNA-strands. Cisplatin having DNA binding ability is loaded in DNA-NT with the aim to achieve enhanced cytotoxicity and cell-internalization mediated by scavenger receptors targeted into Human cervical cancer cells (Hela). DNA nanothread (NT) synthesized by self-assembly of triangular-tiles made from annealing staple-strands with the circularized scaffold-strand. DNA-NT structures and integrity characterized by AFM and Native-PAGE. Cisplatin binding to the DNA-NT confirmed by UV-shift. The biocompatibility of DNA-NT and in-vitro cytotoxic studies of Cisplatin/DNA-NT assessed by MTT. Flow cytometry to quantify the effects of Cisplatin/DNA on cell-cycle phase arrest and apoptosis. The internalization of Cisplatin/DNA-NT in the cells was imaged by confocal microscopy. AFM results showed uniform DNA nanothread structures with a diameter ranging from 50 to 150nm with 300 to 600nm length. Strength/integrity of DNA nanothread was evaluated through PAGE (native), DNA nanothread being stable structure did not split into constituting strands. The results of cell viability confirmed that blank DNA-NT had the least cytotoxicity at the highest concentration with the retained value of 92% as evidence to be biocompatible nanocarrier for drug delivery. While in-vitro cytotoxicity assessment of Cisplatin/DNA-NT displayed increased anticancer activity. Flow cytometry experiments with the Cisplatin/DNA-NT increased the percentage of apoptotic cells significantly in a dose-dependent manner. Moreover, in Confocal microscopy assay, Cisplatin loaded DNA nanothread seems to efficiently deliver Cisplatin to the Hela cell nuclei. 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. We find that being poly-anionic nature, Cisplatin/DNA-NT show enhanced endocytosis via scavenger receptors causing intracellular drug release and enhanced cytotoxicity, which boost the cancer targeting and therapy.