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Non‐Covalently Pre‐Assembled High‐Performance Near‐Infrared Fluorescent Molecular Probes for Cancer Imaging
journal contribution
posted on 2018-10-26, 00:00 authored by Bradley D SmithBradley D Smith, Canjai Zhai, Cesar Fernando Azael Gomez Duran, Cynthia Schreiber, Felicia Roland, Maria de Lourdes Betancourt Mendiola, Scott Shaw, Simon Padanilam, Wenqi LiuNew 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.
History
Date Modified
2018-12-07Language
- English
Publisher
WileyAdditional Groups
- Integrated Imaging Facility
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