Designed DNA nanostructure grafted with erlotinib for non-small-cell lung cancer therapy

Abstract

Chemotherapy for non-small-cell lung cancer (NSCLC) treatment has been employed over the past 20 years. However, poor water-solubility, low bioavailability and less drug accumulation of chemotherapeutic drugs restrict its antitumor activities in clinic. DNA nanostructures are proposed as drug carriers due to their intrinsic biocompatibility and programmability. In this work, we demonstrate a novel DNA nanocarrier grafted with erlotinib as an effective drug delivery system (DDS) for anti-cancer treatment. Specifically, erlotinib (Er), a hydrophobic small molecule drug targeting the epidermal growth factor receptor (EGFR), is covalently conjugated with azide (N₃) modified DNA strands and subsequently self-assembled on spatially programmable erlotinib-grafted 6 × 6 × 64 nt DNA nanostructures. Thus, Er was successfully grafted on DNA carriers and transformed into a hydrophilic formulation. The antitumor efficacy was evaluated both in vitro and in vivo, and enhanced cytotoxicity toward A549 cells and the marked inhibition of tumor growth for non-small-cell lung cancer (NSCLC) were observed.