Journal
ACS NANO
Volume 7, Issue 11, Pages 9724-9734Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn4030543
Keywords
DNA nanocage; controlled encapsulation and release; drug delivery; temperature; MD simulation; fluorescence-quenching; self-assembly
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Funding
- Aase og Ejnar Danielsens Foundation
- Fabrikant Einar Willumsens Mindelegat
- Friedrich Wilhelm Frank & Hustru Angelina Franks Mindelegat
- Arvid Nilssons Foundation
- Minister Erna Hamiltons Legat for Videnskab og Kunst
- Familien Erichsens Mindefond
- Lundbeck Foundation [R95-A10275]
- Danish Council for Independent Research's research carrier program Sapere Aude
- Danish Research Council [11-105736/F5S]
- PRACE Project [2012071230]
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We demonstrate temperature-controlled encapsulation and release of the enzyme horseradish peroxidase using a preassembled and covalently closed three-dimensional DNA cage structure as a controllable encapsulation device. The utilized cage structure was covalently closed and composed of 12 double-stranded B-DNA helices that constituted the edges of the structure. The double stranded helices were interrupted by short single-stranded thymidine linkers constituting the cage corners except for one, which was composed by four 32 nucleotide long stretches of DNA with a sequence that allowed them to fold into hairpin structures. As demonstrated by gel-electrophoretic and fluorophore-quenching experiments this design imposed a temperature-controlled conformational transition capability to the structure, which allowed entrance or release of an enzyme cargo at 37 degrees C while ensuring retainment of the cargo in the central cavity of the cage at 4 degrees C. The entrapped enzyme was catalytically active inside the DNA cage and was able to convert substrate molecules penetrating the apertures in the DNA lattice that surrounded the central cavity of the cage.
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