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

Cho Y, Lee JB, Hong J - Sci Rep (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 1] School of Materials Science and Engineering, Georgia Institute of Technology, 771 Ferst Drive, Atlanta, GA 30332, USA [2].

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.

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Related in: MedlinePlus

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.
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f1: 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.

Mentions: Fig. 1 shows schematics of various DNA structures of H-DNA, Y-DNA, and X-DNA and the preparation of multilayer films consisting of PLL and Dox-incorporated DNAs. DNA is highly biodegradable due to the presence of nucleases. The degraded products are nucleotides, naturally occurring metabolites in the body, making them non-toxic and biocompatible, ideal characteristics for a biomaterial. In addition, DNA can be designed and engineered in a highly controlled manner and high purity and reaction yields can be achieved with extremely precise control, allowing easy control of their physical and chemical properties, even though DNA in nature only have linear or circular forms2181920212223. DNA is thus a highly useful nanomaterial and building block for nano-assembly systems including multilayered structures. H-DNA, branched Y-DNA, and branched X-DNA were synthesized according to previously published methods2425. The successful formation of Y-DNA and X-DNA was confirmed by gel electrophoresis (Fig. S1, supplementary information (SI)). Branched DNA can overcome the structural and topological limitations of conventional linear DNA. First, branched DNA can contain various functional moieties on each branch and are inherently multivalent. Furthermore, the binding affinities and stability of synthesized branched DNAs are controlled by their design172425. Table 1 shows the DNA sequences of DNA used in the present study. Since Dox molecules are appropriate in size and chemical properties to fit between DNA base pairs, Dox can be incorporated into synthesized DNA structure by intercalation, which has been intensively studied before2627. PLL, serving as counter building block with DNA, is natural homopolymer. It is a weak polyelectolyte with pKa value of around 9–10282930, indicating electrostatic interaction between positively charged PLL and negatively charged DNA, which is main driving force for PLL and DNA to form nanofilm structure, can be modulated by external pH conditions after film construction. Assembly of thin films consisting of Dox-incorporated DNA and PLL was performed by the LbL deposition method. Table 2 shows the thickness of thin films composed of 20 bilayers as measured by a profilometer, indicating successful preparation of multilayered thin structures. It shows linear film growth with the number of bilayers and each (PLL/DNA) bilayer thickness is approximately 22, 26, and 27 nm for H-, Y-, and X-DNA, respectively. It is believed that the difference in film thickness of (PLL/H, Y, and X-DNA) arose from their different DNA dimension when considering synthesized DNAs have different length and the number of binding sites, yielding various DNA topologies. The length of one helical turn of double-stranded DNA (dsDNA) consists of ten base pairs is 3.4 nm and its width is 2 nm. Furthermore, the thin film surfaces were analyzed by atomic force microscopy (AFM) as shown in Fig. 2. Since synthesized DNA structures have different sizes and molecular properties, resulting in slightly different PLL adsorption behaviors, they also have different surface roughness and uniformity properties. AFM images, however, indicate the thin film structures were successfully and homogeneous created.


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

Cho Y, Lee JB, Hong J - Sci Rep (2014)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921640&req=5

f1: 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.
Mentions: Fig. 1 shows schematics of various DNA structures of H-DNA, Y-DNA, and X-DNA and the preparation of multilayer films consisting of PLL and Dox-incorporated DNAs. DNA is highly biodegradable due to the presence of nucleases. The degraded products are nucleotides, naturally occurring metabolites in the body, making them non-toxic and biocompatible, ideal characteristics for a biomaterial. In addition, DNA can be designed and engineered in a highly controlled manner and high purity and reaction yields can be achieved with extremely precise control, allowing easy control of their physical and chemical properties, even though DNA in nature only have linear or circular forms2181920212223. DNA is thus a highly useful nanomaterial and building block for nano-assembly systems including multilayered structures. H-DNA, branched Y-DNA, and branched X-DNA were synthesized according to previously published methods2425. The successful formation of Y-DNA and X-DNA was confirmed by gel electrophoresis (Fig. S1, supplementary information (SI)). Branched DNA can overcome the structural and topological limitations of conventional linear DNA. First, branched DNA can contain various functional moieties on each branch and are inherently multivalent. Furthermore, the binding affinities and stability of synthesized branched DNAs are controlled by their design172425. Table 1 shows the DNA sequences of DNA used in the present study. Since Dox molecules are appropriate in size and chemical properties to fit between DNA base pairs, Dox can be incorporated into synthesized DNA structure by intercalation, which has been intensively studied before2627. PLL, serving as counter building block with DNA, is natural homopolymer. It is a weak polyelectolyte with pKa value of around 9–10282930, indicating electrostatic interaction between positively charged PLL and negatively charged DNA, which is main driving force for PLL and DNA to form nanofilm structure, can be modulated by external pH conditions after film construction. Assembly of thin films consisting of Dox-incorporated DNA and PLL was performed by the LbL deposition method. Table 2 shows the thickness of thin films composed of 20 bilayers as measured by a profilometer, indicating successful preparation of multilayered thin structures. It shows linear film growth with the number of bilayers and each (PLL/DNA) bilayer thickness is approximately 22, 26, and 27 nm for H-, Y-, and X-DNA, respectively. It is believed that the difference in film thickness of (PLL/H, Y, and X-DNA) arose from their different DNA dimension when considering synthesized DNAs have different length and the number of binding sites, yielding various DNA topologies. The length of one helical turn of double-stranded DNA (dsDNA) consists of ten base pairs is 3.4 nm and its width is 2 nm. Furthermore, the thin film surfaces were analyzed by atomic force microscopy (AFM) as shown in Fig. 2. Since synthesized DNA structures have different sizes and molecular properties, resulting in slightly different PLL adsorption behaviors, they also have different surface roughness and uniformity properties. AFM images, however, indicate the thin film structures were successfully and homogeneous created.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 1] School of Materials Science and Engineering, Georgia Institute of Technology, 771 Ferst Drive, Atlanta, GA 30332, USA [2].

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.

Show MeSH
Related in: MedlinePlus