The PEG-Fluorochrome Shielding Approach for Targeted Probe Design

• Published in: Journal of the American Chemical Society Vol. 134; no. 47; pp. 19338 - 19341
• Main Authors: Guo, Yanyan, Yuan, Hushan, Rice, William L, Kumar, Anand T. N, Goergen, Craig J, Jokivarsi, Kimmo, Josephson, Lee
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 28.11.2012; Amer Chemical Soc
• Subjects: absorption; Animals; Cell Line, Tumor; chemical bonding; Chemistry; Chemistry, Multidisciplinary; fluorescence; fluorescent dyes; Fluorescent Dyes - administration & dosage; Fluorescent Dyes - chemistry; Humans; integrins; Mice; Molecular Probes - administration & dosage; Molecular Probes - chemical synthesis; Molecular Structure; Peptides - administration & dosage; Peptides - chemical synthesis; Physical Sciences; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - chemistry; Science & Technology; NANOPARTICLE; CANCER; DYES
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/ja309085b

We provide a new approach for fluorescent probe design termed “PEG-fluorochrome shielding”, where PEGylation enhances quantum yields while blocking troublesome interactions between fluorochromes and biomolecules. To demonstrate PEG-fluorochrome shielding, fluorochrome-bearing peptide probes were synthesized, three without PEG and three with a 5 kDa PEG functional group. In vitro, PEG blocked the interactions of fluorochrome-labeled peptide probes with each other (absorption spectra, self-quenching) and reduced nonspecific interactions with cells (by FACS). In vivo, PEG blocked interactions with biomolecules that lead to probe retention (by surface fluorescence). Integrin targeting in vivo was obtained as the differential uptake of an 111In-labeled, fluorochrome-shielded, integrin-binding RGD probe and a control RAD. Using PEG to block fluorochrome-mediated interactions, rather than synthesizing de novo fluorochromes, can yield new approaches for the design of actively or passively targeted near-infrared fluorescent probes.