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Different PEG‐PLGA Matrices Influence In Vivo Optical/Photoacoustic Imaging Performance and Biodistribution of NIR‐Emitting π ‐Conjugated Polymer Contrast Agents
Author(s) -
Neumann Paul Robert,
Erdmann Frank,
Holthof Joost,
Hädrich Gabriela,
Green Mark,
Rao Jianghong,
Dailey Lea Ann
Publication year - 2021
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202001089
Subject(s) - biodistribution , plga , peg ratio , conjugated system , materials science , polyethylene glycol , in vivo , absorption (acoustics) , polymer , biophysics , nanoparticle , chemistry , nanotechnology , organic chemistry , microbiology and biotechnology , finance , economics , composite material , biology
The π ‐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.