Counterion-insulated near-infrared dyes in biodegradable polymer nanoparticles for in vivo imaging

Joanna Sobska (1) , Bohdan Andreiuk (2) , Ilia Aparin (2) , Andreas Reisch (2) , Wojciech Krezel (1) , Andrey Klymchenko (2)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 LBP - Laboratoire de Bioimagerie et Pathologies

Bulky hydrophobic counterions were applied for encapsulation of near-infrared cyanine dyes into biodegradable polymer matrix with minimized self-quenching, yielding fluorescent nanoparticles with stealth PEG shell for in vivo imaging. , Polymeric nanoparticles (NPs) are highly attractive for biomedical applications due to their potential biodegradability and capacity to encapsulate different loads, notably drugs and contrast agents. For in vivo optical bioimaging, NPs should operate in the near-infrared region (NIR) and exhibit stealth properties. In the present work, we applied the approach of ionic dye insulation with bulky hydrophobic counterions for encapsulation of near-infrared cyanine dyes (Cy5.5 and Cy7 bearing two octadecyl chains) into biodegradable polymer (PLGA) NPs. We found that at high dye loading (20–50 mM with respect to the polymer), the bulkiest fluorinated tetraphenylborate counterion minimized best the aggregation-caused quenching and improved fluorescence quantum yields of both NIR dyes, especially of Cy5.5. In addition, bulky counterions also enabled formation of small 40 nm polymeric NPs in contrast to smaller counterions. To provide them stealth properties, we prepared 40 nm dye-loaded PEGylated NPs through nanoprecipitation of synthetic PLGA–PEG block copolymer with the dye/counterion salt. The obtained NIR NPs loaded with Cy5.5 dye salt allowed in vivo imaging of wild-type mice with a good contrast after IV injection. Compared to the bare PLGA NPs, PLGA–PEG NPs exhibited significantly slower accumulation in the liver. Biodistribution studies confirmed the preferential accumulation in the liver, although PLGA and PLGA–PEG NPs could also be distributed in other organs, with the following tendency: liver > spleen > lungs > kidney > heart > testis > brain. Overall, the present work validated the counterion approach for encapsulation of NIR cyanine dyes into biodegradable polymer NPs bearing covalently attached PEG shell. Thus, we propose a simple and robust methodology for preparation of NIR fluorescent biodegradable polymer NPs, which could further improve the existing optical imaging for biomedical applications.

Domaines: Biologie cellulaire

Joanna Sobska, Bohdan Andreiuk, Ilia Aparin, Andreas Reisch, Wojciech Krezel, et al.. Counterion-insulated near-infrared dyes in biodegradable polymer nanoparticles for in vivo imaging. Nanoscale Advances, 2022, 4 (1), pp.39-48. ⟨10.1039/D1NA00649E⟩. ⟨hal-03637859⟩