Journal
ADVANCED HEALTHCARE MATERIALS
Volume 10, Issue 4, Pages -Publisher
WILEY
DOI: 10.1002/adhm.202001089
Keywords
conjugated polymer nanoparticles; PCPDTBT; PEG-PLGA; photoacoustic imaging
Funding
- German Academic Exchange Program (DAAD) [57381316]
- Stanford Animal Diagnostic Laboratory-blood sampling, hematology, clinical chemistry, and dissection of animals
- EPSRC [EP/K018876/1] Funding Source: UKRI
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This study investigated the use of PCPDTBT as a contrast agent for optical imaging, examining the impact of different encapsulation methods on imaging performance, biodistribution, and biocompatibility. Results showed that formulations have a significant impact on both imaging performance and biodistribution, indicating the importance of further exploration in this area.
The pi-conjugated polymer poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b0]-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT) with deep-red/near-infrared (NIR) absorption and emission has been investigated as a contrast agent for in vivo optical and photoacoustic imaging. PCPDTBT is encapsulated within poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG(2kDa)-PLGA(4kDa)or PEG(5kDa)-PLGA(55kDa)) micelles or enveloped by the phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (PEG(2kDa)-DPPE), to investigate the formulation effect on imaging performance, biodistribution, and biocompatibility. Nanoparticles that meet the quality requirements for parenteral administration are generated with similar physicochemical properties. Optical phantom imaging reveals that both PEG-PLGA systems exhibit a 30% higher signal-to-background ratio (SBR) than PEG(2kDa)-DPPE. This trend cannot be observed in a murine HeLa xenograft model following intravenous administration since dramatic differences in biodistribution are observed. PEG(2kDa)-PLGA(4kDa)systems accumulate more rapidly in the liver compared to other formulations and PEG(2kDa)-DPPE demonstrates a higher tumor localization. Protein content in the hard corona differs between formulations (PEG(2kDa)-DPPE < PEG(2kDa)-PLGA(4kDa)< PEG(5kDa)-PLGA(55kDa)), although this observation alone does not explain biodistribution patterns. PEG(2kDa)-PLGA(4kDa)systems show the highest photoacoustic amplitude in a phantom, but also a lower signal in the tumor due to differences in biodistribution. This study demonstrates that formulations for conjugated polymer contrast agents can have significant impact on both imaging performance and biodistribution.
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