Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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An Activatable Fluorescent γ-Polyglutamic Acid Complex for Sentinel Lymph Node Imaging
Masayori HagimoriEri HatabeKohei SanoHirotaka MiyazakiHitoshi SasakiHideo SajiTakahiro Mukai
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2017 Volume 40 Issue 3 Pages 297-302

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Abstract

Sentinel lymph nodes (SLN) are the first lymph nodes (LN) where cancer cells metastasize from the primary tumor. We designed fluorophore-quencher-based activatable nanoparticles for SLN imaging. We selected TAMRA as a fluorophore and BHQ2 or QSY7 as a quencher. Ternary anionic complexes were constructed with generation 4th polyamidoamine dendrimer (G4) modified with TAMRA and p-SCN-Bn-DTPA (DTPA), polyethyleneimine (PEI) modified with BHQ2 or QSY7, and γ-polyglutamic acid (γ-PGA) by the electrostatic self-assembly system. TAMRA-G4-DTPA/PEI-BHQ2/γ-PGA and TAMRA-G4-DTPA/PEI-QSY7/γ-PGA complexes had a particle size of about 40 nm and a ζ-potential of −50 mV, and showed fluorescence resonance energy transfer (FRET) quenching. Fluorescence microscopy studies demonstrated that TAMRA-G4-DTPA/PEI-QSY7/γ-PGA complex produced intracellular fluorescent signals in the lysosome. During in vivo fluorescent imaging, TAMRA-G4-DTPA/PEI-QSY7/γ-PGA complex enabled the detection of mouse popliteal LN. The fluorophore-quencher conjugated γ-PGA complex based on FRET quenching would be useful for fluorescence-based optical imaging of SLN.

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© 2017 The Pharmaceutical Society of Japan
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