title: An Activatable Fluorescent γ-Polyglutamic Acid Complex for Sentinel Lymph Node Imaging.
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.
authors.affiliation: Department of Biophysical Chemistry, Kobe Pharmaceutical University.
authors.forename: Masayori
authors.initials: M
authors.lastname: Hagimori
authors.forename: Eri
authors.initials: E
authors.lastname: Hatabe
authors.forename: Kohei
authors.initials: K
authors.lastname: Sano
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mukai
mesh_terms: D000818:Animals; D050091:Dendrimers; D005453:Fluorescence; D005456:Fluorescent Dyes; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000000981:diagnostic imaging; D008247:Lysosomes; D008297:Male; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D061848:Optical Imaging / Q000379:methods*; D010316:Particle Size; D004369:Pentetic Acid; D011073:Polyamines; D011094:Polyethyleneimine; D011099:Polyglutamic Acid / Q000031:analogs & derivatives*; D012235:Rhodamines; D000071036:Sentinel Lymph Node / Q000000981:diagnostic imaging*
chemical_list: C114557:5-carboxytetramethylrhodamine succinimidyl ester; D050091:Dendrimers; D005456:Fluorescent Dyes; C531249:Poly(amidoamine); D011073:Polyamines; D012235:Rhodamines; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D004369:Pentetic Acid; D011094:Polyethyleneimine