Controlled release of an anti-cancer drug from DNA structured nano-films

Abstract

We demonstrate the generation of systemically releasable anti-cancer drugs from multilayer nanofilms. Nanofilms designed to drug release profiles in programmable fashion are promising new and alternative way for drug delivery. For the nanofilm structure, we synthesized various unique 3-dimensional anti cancer drug incorporated DNA origami structures (hairpin, Y, and X shaped) and assembled with peptide via layer-by-layer (LbL) deposition method. The key to the successful application of these nanofilms requires a novel approach of the influence of DNA architecture for the drug release from functional nano-sized surface. Herein, we have taken first steps in building and controlling the drug incorporated DNA origami based multilayered nanostructure. Our finding highlights the novel and unique drug release character of LbL systems in serum condition taken full advantages of DNA origami structure. This multilayer thin film dramatically affects not only the release profiles but also the structure stability in protein rich serum condition.

Figure 1. Schematic illustration of (a) hair-pin-, Y-, and X-shaped DNA, (b) multilayer assembly combination of Dox encapsulated DNA and PLL, and (c) experimental procedure.

Figure 2. Height mode AFM images of a) (PLL/hairpin)₂₀, b) (PLL/Y-DNA)₂₀, and c) (PLL/X-DNA)₂₀.

Figure 3

a) The total amount and b) cumulative normalized release profile of Doxorubicin from DNA incorporated LbL films as a function of incubation time after rehydration in FBS (pH 7.4 at 37°C, 5% CO₂).