Expanding analytical tools for characterizing ultrasmall silica-based nanoparticles Journal Article


Authors: Yoo, B.; Ma, K.; Wiesner, U.; Bradbury, M.
Article Title: Expanding analytical tools for characterizing ultrasmall silica-based nanoparticles
Abstract: C′ dots are fluorescent inorganic-organic hybrid nanoparticles synthesized in water comprised of a silica core with a covalently embedded near infrared dye, and a polyethylene glycol (PEG) outer layer. C′ dots containing the integrin specific ligand, cycloRGDyC, are the first of their kind particles approved for human clinical trials. In the continued clinical development of these nanoparticles, high-resolution analytical approaches are needed. Here we investigate the use of reversed phase high performance liquid chromatography (RP-HPLC) to analyze cycloRGDyC-Cy5-C′ dots. Given the stability and protein-like size, we reasoned that these nanoparticles would be compatible under RP-HPLC conditions typically used to characterize peptides and proteins. Our results show that RP-HPLC provides excellent resolution, showing significant heterogeneity of these nanoparticles. C′ dots also exhibit unusual peak profiles where RP-HPLC chromatogram peak shapes change from run to run, possibly due to the conformational heterogeneity or charge distribution of the particle surface due to the PEG groups. In addition we describe a novel thiol-mediated release of C′ dot ligands to directly estimate cycloRGDyC by exposing the particles to organic thiols. Ligand release is presumably afforded by a reverse Michael reaction mechanism. © The Royal Society of Chemistry.
Keywords: proteins; ligands; nanoparticles; silica; high performance liquid chromatography; liquid chromatography; synthesis (chemical); conformational heterogeneity; near-infrared dyes; infrared devices; clinical development; chromatographic analysis; addition reactions; analytical approach; inorganic-organic hybrid; mediated release; michael reactions; reversed-phase high-performance liquid chromatography
Journal Title: RSC Advances
Volume: 7
Issue: 27
ISSN: 2046-2069
Publisher: Royal Society of Chemistry  
Date Published: 2017-01-01
Start Page: 16861
End Page: 16865
Language: English
DOI: 10.1039/c7ra01349c
PROVIDER: scopus
PMCID: PMC5607868
PUBMED: 28944051
DOI/URL:
Notes: Correction issued, see DOI: 10.1039/c8ra90077a -- Article -- Export Date: 2 May 2017 -- Source: Scopus
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  1. Barney Yoo
    13 Yoo