Low molecular weight PEG-PLGA polymers provide a superior matrix for conjugated polymer nanoparticles in terms of physicochemical properties, biocompatibility and optical/photoacoustic performance

The near-infrared absorbing conjugated polymer poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b ']-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT) has been investigated as a contrast agent for optical and photoacoustic imaging. Lipophilic pi-conjugated polymers can be efficiently encapsulated within self-assembling diblock copolymer poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles, although the effect of variations in PEG and PLGA chain lengths on nanoparticle properties, performance and biocompatibility have not yet been investigated. In this study, PEG-PLGA with different block lengths (PEG(2kDa)-PLGA(4kDa), PEG(2kDa)-PLGA(15kDa) and PEG(5kDa)-PLGA(55kDa)) were used to encapsulate PCPDTBT. Nanoparticle sizes were smallest (<100 nm) when using PEG(2kDa)-PLGA(4kDa), with <5% PCPDTBT content and a reduction in the total solids concentration of the organic phase. All PEG-PLGA nanoparticles were colloidally stable in water and serum-supplemented cell culture medium over 24 h at 37 degrees C, with slight evidence of protein surface adsorption. PEG(2kDa)-PLGA(4kDa) systems showed a threefold lower cytotoxicity (IC50 value) than the other two systems. Haemolytic activity was <2.5% for all systems and no platelet aggregation or inhibition of ADP-induced platelet aggregation was observed. Encapsulation of PCPDTBT within a PEG-PLGA matrix shifted fluorescence emission towards red wavelengths (760 nm in THF vs. 840 nm in nanoparticles) and reduced the quantum yield by 30-70-fold compared to THF. Nonetheless, PCPDTBT:PEG(2kDa)-PLGA(4kDa) systems had a marginally higher quantum yield and signal-to-background ratio in a phantom mouse compared with PEG(2kDa)-PLGA(15kDa) and PEG(5kDa)-PLGA(55kDa) systems. As a photoacoustic imaging probe, PCPDTBT:PEG(2kDa)-PLGA(4kDa) systems also showed a higher photoacoustic amplitude compared to higher molecular weight PEG-PLGA systems. Overall, the low molecular weight PEG(2kDa)-PLGA(4kDa) nanoparticle systems conferred the benefits of smaller sizes, reduced cytotoxicity and enhanced imaging performance compared to higher molecular weight matrix polymers.