Journal article
Non‐Covalently Pre‐Assembled High‐Performance Near‐Infrared Fluorescent Molecular Probes for Cancer Imaging
Chemistry : a European journal, Vol.24(52), pp.13821-13829
09/18/2018
DOI: 10.1002/chem.201801825
PMCID: PMC6415912
PMID: 30022552
Abstract
New fluorescent molecular probes, which can selectively target specific cell surface receptors, are needed for microscopy, in vivo imaging, and image guided surgery. The preparation of multivalent probes using standard synthetic chemistry can be a laborious process due to low reaction yields caused by steric effects. In this study, fluorescent molecular probes were prepared by a programmed non‐covalent pre‐assembly process that used a near‐infrared fluorescent squaraine dye to thread a macrocycle bearing a cyclic arginine‐glycine‐aspartate peptide antagonist (cRGDfK) as a cancer targeting unit. Cell microscopy studies using OVCAR‐4 (ovarian cancer) and A549 (lung cancer) cells that express high levels of the integrin αvβ3 or αvβ5 receptors, respectively, revealed a multivalent cell targeting effect. That is, there was comparatively more cell uptake of a pre‐assembled probe equipped with two copies of the cRGDfK antagonist than a pre‐assembled probe with only one appended cRGDfK antagonist. The remarkably high photostability and low phototoxicity of these near‐infrared probes allowed for acquisition of long‐term fluorescence movies showing endosome trafficking in living cells. In vivo near‐infrared fluorescence imaging experiments compared the biodistribution of a targeted and untargeted probe in a xenograft mouse tumor model. The average tumor‐to‐muscle ratio for the pre‐assembled targeted probe was 3.6 which matches the tumor targeting performance reported for analogous cRGDfK‐based probes that were prepared entirely by covalent synthesis. The capability to excite these pre‐assembled near‐infrared fluorescent probes with blue or deep‐red excitation light makes it possible to determine if a target site is located superficially or buried in tissue, a probe performance feature that is likely to be very helpful for eventual applications such as fluorescence guided surgery.
A macrocycle bearing a cancer‐targeting peptide is used to pre‐assemble highly photostable near‐infrared fluorescent molecular probes for cancer imaging in cells or living subjects.
Details
- Title: Subtitle
- Non‐Covalently Pre‐Assembled High‐Performance Near‐Infrared Fluorescent Molecular Probes for Cancer Imaging
- Creators
- Scott K Shaw - University of Notre DameWenqi Liu - University of Notre DameCésar Fernando Azael Gómez Durán - University of Notre DameCynthia L Schreiber - University of Notre DameMaría de Lourdes Betancourt Mendiola - University of Notre DameCanjia Zhai - University of Notre DameFelicia M Roland - University of Notre DameSimon J Padanilam - University of Notre DameBradley D Smith - University of Notre Dame
- Resource Type
- Journal article
- Publication Details
- Chemistry : a European journal, Vol.24(52), pp.13821-13829
- DOI
- 10.1002/chem.201801825
- PMID
- 30022552
- PMCID
- PMC6415912
- NLM abbreviation
- Chemistry
- ISSN
- 0947-6539
- eISSN
- 1521-3765
- Number of pages
- 9
- Grant note
- Office of Extramural Research, National Institutes of Health (GM059078; GM075762)
- Language
- English
- Date published
- 09/18/2018
- Academic Unit
- Chemistry
- Record Identifier
- 9984216607202771
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