Target-specific nanoparticles containing a broad band emissive NIR dye for the sensitive detection and characterization of tumor development.
Current optical probes including engineered nanoparticles (NPs) are constructed from near infrared (NIR)-emissive organic dyes with narrow absorption and emission bands and small Stokes shifts prone to aggregation-induced self-quenching. Here, we present the new asymmetric cyanine Itrybe with broad, almost environment-insensitive absorption and emission bands in the diagnostic window, offering a unique flexibility of the choice of excitation and detection wavelengths compared to common NIR dyes. This strongly emissive dye was spectroscopically studied in different solvents and encapsulated into differently sized (15, 25, 100 nm) amino-modified polystyrene NPs (PSNPs) via a one-step staining procedure. As proof-of-concept for its potential for pre-/clinical imaging applications, Itrybe-loaded NPs were surface-functionalized with polyethylene glycol (PEG) and the tumor-targeting antibody Herceptin and their binding specificity to the tumor-specific biomarker HER2 was systematically assessed. Itrybe-loaded NPs display strong fluorescence signals in vitro and in vivo and Herceptin-conjugated NPs bind specifically to HER2 as demonstrated in immunoassays as well as on tumor cells and sections from mouse tumor xenografts in vitro. This demonstrates that our design strategy exploiting broad band-absorbing and -emitting dyes yields versatile and bright NIR probes with a high potential for e.g. the sensitive detection and characterization of tumor development and progression.
BAM Federal Institute for Materials Research and Testing, 1.10, Richard-Willstätter-Str. 11, 12489 Berlin, Germany.
Thomas
T
Behnke
Julia E
JE
Mathejczyk
Robert
R
Brehm
Christian
C
Würth
Fernanda Ramos
FR
Gomes
Christian
C
Dullin
Joanna
J
Napp
Frauke
F
Alves
Ute
U
Resch-Genger
D016475:3T3 Cells; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D004396:Coloring Agents / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D010316:Particle Size; D011137:Polystyrenes / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012997:Solvents; D019265:Spectroscopy, Near-Infrared; D023041:Xenograft Model Antitumor Assays
D004396:Coloring Agents; D005456:Fluorescent Dyes; D011137:Polystyrenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D012997:Solvents