Nucleic Acid Nanocapsules for Enzyme-Triggered Drug Release

被引:71
作者
Awino, Joseph K. [1 ]
Gudipati, Saketh [1 ]
Hartmann, Alyssa K. [1 ]
Santiana, Joshua J. [1 ]
Cairns-Gibson, Dominic F. [1 ]
Gomez, Nicole [1 ]
Rouge, Jessica L. [1 ]
机构
[1] Univ Connecticut, Dept Chem, Storrs, CT 06269 USA
关键词
IN-VIVO; ANTISENSE OLIGONUCLEOTIDES; DELIVERY; RNA; DNAZYME; CELLS; CAMPTOTHECIN; DISCOVERY; APOPTOSIS; CATALYSIS;
D O I
10.1021/jacs.6b13087
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Herein we describe a nucleic acid functionalized nanocapsule in which nucleic acid ligands are assembled and disassembled in the presence of enzymes. The particles are fully degradable in response to esterases due to an embedded ester cross-linker in the particle's core. During synthesis the nanocapsules can be loaded with hydrophobic small molecules and post self-assembly undergo covalent cross-linking using copper catalyzed click chemistry. They can then be functionalized with thiolated DNA through stepwise thiolyne chemistry using UV light irradiation. Additionally, the capsule is compatible with enzyme mediated functionalization of a therapeutic mRNA-cleaving DNAzyme at the particle's surface. The resulting particle is highly stable, monodisperse in size, and maximizes the therapeutic potential of both the particles interior and exterior.
引用
收藏
页码:6278 / 6281
页数:4
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