Gold, poly(β-amino ester) nanoparticles for small interfering RNA delivery

Jae Seung Lee; Jordan J. Green; Kevin T. Love; Joel Sunshine; Robert Langer; Daniel G. Anderson

doi:10.1021/nl9009793

Gold, poly(β-amino ester) nanoparticles for small interfering RNA delivery

Jae Seung Lee, Jordan J. Green, Kevin T. Love, Joel Sunshine, Robert Langer, Daniel G. Anderson

Research output: Contribution to journal › Article › peer-review

256 Citations (Scopus)

Abstract

The safe and effective delivery of RNA therapeutics remains the major barrier to their broad clinical application. Here we develop a new nanoparticulate delivery system based on inorganic particles and biodegradable polycations. First, gold nanoparticles were modified with the hydrophilic polymer poly(ethylene glycol) (PEG), and then small interfering RNA (siRNA) was conjugated to the nanoparticles via biodegradable disulfide linkages, with 30 strands of siRNA per nanoparticle. The particles were then coated with a library of end-modified poly(β-amino ester)s (PBAEs), previously identified as capable of facilitating intracellular DNA delivery. Nanoparticulate formulations developed here facilitate high levels of in vitro siRNA delivery, facilitating delivery as good or better than the commercially available lipid reagent, Lipofectamine 2000.

Original language	English
Pages (from-to)	2402-2406
Number of pages	5
Journal	Nano Letters
Volume	9
Issue number	6
DOIs	https://doi.org/10.1021/nl9009793
Publication status	Published - 2009 Jun 10

ASJC Scopus subject areas

Bioengineering
Chemistry(all)
Materials Science(all)
Condensed Matter Physics
Mechanical Engineering

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AU - Sunshine, Joel

AU - Langer, Robert

AU - Anderson, Daniel G.

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AB - The safe and effective delivery of RNA therapeutics remains the major barrier to their broad clinical application. Here we develop a new nanoparticulate delivery system based on inorganic particles and biodegradable polycations. First, gold nanoparticles were modified with the hydrophilic polymer poly(ethylene glycol) (PEG), and then small interfering RNA (siRNA) was conjugated to the nanoparticles via biodegradable disulfide linkages, with 30 strands of siRNA per nanoparticle. The particles were then coated with a library of end-modified poly(β-amino ester)s (PBAEs), previously identified as capable of facilitating intracellular DNA delivery. Nanoparticulate formulations developed here facilitate high levels of in vitro siRNA delivery, facilitating delivery as good or better than the commercially available lipid reagent, Lipofectamine 2000.

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Gold, poly(β-amino ester) nanoparticles for small interfering RNA delivery

Abstract

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