Abstract
Borylated poly(fluorene-benzothiadiazoles) (PF8-BT) are π-conjugated polymers (CPs) with deep-red/near-infrared (NIR) absorption and emission profiles suitable for in vivo optical imaging. A fully borylated PF8-BT derivative (P4) was encapsulated in pegylated poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles and compared with a reference NIR-emitting CP (PCPDTBT) or indocyanine green (ICG). All formulations satisfied quality requirements for parenterally administered diagnostics. P4 nanoparticles had higher quantum yield (2.3%) than PCPCDTBT (0.01%) or ICG nanoparticles (1.1%). The signal/background ratios (SBRs) of CP systems P4 and PCPDTBT in a phantom mouse (λem = 820 nm) increased linearly with fluorophore mass (12.5-100 μg/mL), while the SBRs of ICG decreased above 25 μg/mL. P4 nanoparticles experienced <10% photobleaching over 10 irradiations (PCPDTBT: ∼25% and ICG: >44%). In a mouse tumor xenograft model, P4 nanoparticles showed a 5-fold higher SBR than PCPDTBT particles with fluorophore accumulation in the liver > spleen > tumor. Blood chemistry and tissue histology showed no abnormalities compared to untreated animals after a single administration.
Keywords:
PCPDTBT; PEG−PLGA; borylated poly(fluorene-benzothiadiazole); conjugated polymer nanoparticles; critical quality attributes.
MeSH terms
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Animals
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Drug Delivery Systems*
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Fluorenes / chemistry
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Fluorenes / pharmacology
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Fluorescent Dyes / chemistry
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Heterografts
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Humans
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Indocyanine Green / chemistry
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Liver / diagnostic imaging
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Liver / drug effects
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Mice
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Nanoparticles / adverse effects
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Nanoparticles / chemistry*
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Neoplasms / diagnostic imaging*
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Neoplasms / drug therapy
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Neoplasms / pathology
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Photobleaching / drug effects
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Polyesters / chemistry
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Polyethylene Glycols / chemistry
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Polymers / chemistry
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Spleen / diagnostic imaging
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Spleen / drug effects
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Thiadiazoles / adverse effects
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Thiadiazoles / chemistry
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Thiadiazoles / pharmacology*
Substances
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Fluorenes
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Fluorescent Dyes
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Polyesters
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Polymers
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Thiadiazoles
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polyethylene glycol-poly(lactide-co-glycolide)
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benzo-1,2,3-thiadiazole
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fluorene
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Polyethylene Glycols
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Indocyanine Green