Programmable Peptide-Cross-Linked Nucleic Acid Nanocapsules as a Modular Platform for Enzyme Specific Cargo Release

Herein we describe a modular assembly strategy for photo-cross-linking peptides into nucleic acid functionalized nanocapsules. The peptides embedded within the nanocapsules form discrete nanoscale populations capable of gating the release of molecular and nanoscale cargo using enzyme–substrate recog...

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Bibliographic Details
Published in:Bioconjugate chemistry 2017-12, Vol.28 (12), p.2910-2914
Main Authors: Santiana, Joshua J, Sui, Binglin, Gomez, Nicole, Rouge, Jessica L
Format: Article
Language:English
Subjects:
Acids
Assembly
Azides - chemistry
Biological Transport
Biosensors
Cell culture
Cells
Crosslinking
Drug Carriers - chemistry
Drug delivery
Drug delivery systems
Drug Liberation
Enflurane - chemistry
Enzymes
Fluorescence
Gating
Gold - chemistry
Gold - metabolism
HeLa Cells
Humans
Matrix Metalloproteinase 9 - metabolism
Metal Nanoparticles
Microscopy
Nanocapsules - chemistry
Nanoparticles
Nucleic acids
Nucleic Acids - chemistry
Peptides
Peptides - chemistry
Proteases
Substrates
Sulfhydryl Compounds - chemistry
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Summary:Herein we describe a modular assembly strategy for photo-cross-linking peptides into nucleic acid functionalized nanocapsules. The peptides embedded within the nanocapsules form discrete nanoscale populations capable of gating the release of molecular and nanoscale cargo using enzyme–substrate recognition as a triggered release mechanism. Using photocatalyzed thiol–yne chemistry, different peptide cross-linkers were effectively incorporated into the nanocapsules and screened against different proteases to test for degradation specificity both in vitro and in cell culture. By using a combination of fluorescence assays, confocal and TEM microscopy, the particles were shown to be highly specific for their enzyme targets, even between enzymes of similar protease classes. The rapid and modular nature of the assembly strategy has the potential to be applied to both intracellular and extracellular biosensing and drug delivery applications.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.7b00629