期刊
BIOCONJUGATE CHEMISTRY
卷 27, 期 11, 页码 2715-2721出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.6b00483
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资金
- National Cancer Institute of the National Institutes of Health [U54CA151880, U54CA199091]
- NTU-NU Institute for NanoMedicine located at the International Institute for Nanotechnology, Northwestern University (Evanston, IL)
- Nanyang Technological University (Singapore)
- National Defense Science and Engineering Graduate Fellowship
- National Institute Of General Medical Sciences of the National Institutes of Health [T32GM105538, F31GM119392]
- International Institute for Nanotechnology of Northwestern University
Two synthetic approaches that allow one to control PEG content within spherical nucleic acids (SNAs) have been developed. One approach begins with RNA-modified gold nanoparticles followed by a backfill of PEG 2K alkanethiols, and the other involves co-adsorption of the two entities on a gold nanoparticle template. These two methods have been used to explore the role of PEG density on the chemical and biological properties of RNA SNAs. Such studies show that while increasing the extent of PEGylation within RNA-SNAs extends their blood circulation half-life in mice, it also results in decreased cellular uptake. Modified ELISA assays show that constructs, depending upon RNA and PEG content, have markedly different affinities for class A scavenger receptors, the entities responsible, in part, for cellular internalization of SNAs. In designing SNAs for therapeutic purposes, these competing factors must be considered and appropriately adjusted depending upon the desired use.
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